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    Robotic Radical Parametrectomy With Upper Vaginectomy and Pelvic Lymphadenectomy in Patients With Occult Cervical Carcinoma After Extrafascial Hysterectomy. Tran Arthur-Quan,Sullivan Stephanie A,Gehrig Paola A,Soper John T,Boggess John F,Kim Kenneth H Journal of minimally invasive gynecology STUDY OBJECTIVE:To confirm the safety and feasibility outcomes of robotic radical parametrectomy and pelvic lymphadenectomy and compare the clinicopathological features of women requiring adjuvant treatment with the historical literature. DESIGN:Retrospective cohort study and review of literature (Canadian Task Force classification II-2). SETTING:Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill. PATIENTS:All patients who underwent robotic radical parametrectomy with upper vaginectomy (RRPV), and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy at our institution between January 2007 and December 2015. INTERVENTIONS:RRPV and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy. We also performed a literature review of the literature on radical parametrectomy after occult cervical carcinoma. MEASUREMENTS AND MAIN RESULTS:Seventeen patients with invasive carcinoma of the cervix discovered after extrafascial hysterectomy underwent RRPV with bilateral pelvic lymphadenectomy. There were 2 intraoperative complications, including 1 bowel injury and 1 bladder injury. One patient required a blood transfusion of 2 units. Three patients underwent adjuvant treatment with chemoradiation with radiation-sensitizing cisplatin. One of these patients had residual carcinoma on the upper vagina, 1 patient had positive parametria and pelvic nodes, and 1 patient had positive pelvic lymph nodes. No patients experienced recurrence, and 1 patient died from unknown causes at 59.4 months after surgery. We analyzed 15 studies reported in the literature and found 238 women who underwent radical parametrectomy; however, no specific preoperative pathological features predicted outcomes, the need for adjuvant treatment, or parametrial involvement. CONCLUSION:RRPV is a feasible and safe treatment option. As reflected in the literature, RRPV can help avoid empiric adjuvant chemoradiation; however, no pathological features predict the need for adjuvant treatment after surgery. 10.1016/j.jmig.2017.02.016
    New procedures for the identification of sentinel lymph node: shaping the horizon of future management in early stage uterine cervical cancer. Rossetti Diego,Vitale Salvatore Giovanni,Tropea Alessandro,Biondi Antonio,Laganà Antonio Simone Updates in surgery Lymph node metastasis is one of the most important prognostic factors for uterine cervical cancer, although lymph node status is not part of the International Federation of Gynaecology and Obstetrics (FIGO) staging. Considering the increasing attention about the topic, we performed a comprehensive review of the literature, to assess the accuracy of real-time fluorescence sentinel lymph node (SLN) for the detection of nodal metastases in patients with early stage cervical cancer (ESCC). In this work, we discuss the different techniques for SLN mapping and the accuracy of each one of them and, basing on these data, summarize the most important recommendations. In particular, we suggest to perform indocyanine green-SLN technique for ESCC, since it showed the highest accuracy for the detection of nodal metastases. 10.1007/s13304-017-0456-6
    Neo-adjuvant platinum-based chemotherapy followed by chemoradiation and radical surgery in locally advanced cervical cancer (Lacc) patients: A phase II study. Ferrandina Gabriella,Palluzzi Eleonora,Gallotta Valerio,Gambacorta Maria Antonietta,Autorino Rosa,Turco Luigi Carlo,Macchia Gabriella,Cosentino Francesco,Gui Benedetta,Mattoli Maria Vittoria,Ronzino Graziana,Valentini Vincenzo,Scambia Giovanni European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology PURPOSE:The aim of this Phase II, non-randomized study was to assess activity and safety of neoadjuvant chemotherapy (NACT) before chemoradiation (CT/RT) followed by radical surgery (RS) in locally advanced cervical cancer (LACC) patients. METHODS AND MATERIALS:The primary end point was rate of pathologic complete response (pCR). FIGO Stage IB2-IVA patients were administered NACT chemotherapy (paclitaxel 80 mg/m, carboplatin AUC 2), for 6 weeks, followed by Intensity Modulated Radiotherapy plus simultaneous boost (total dose of 50.4 Gy to CTV1, and 39.6 Gy to CTV2). Clinical response was assessed according to RECIST criteria. Responsive patients were triaged to RS. The regimen would be considered active if >20 pCRs were registered in 39 patients. RESULTS:45 patients were enrolled into the study; 25 patients (55.5%) were FIGO stage IIB, 9 cases (20.0%) had stage III disease. At work up, pelvic lymph node involvement was documented in 38 (84.4%) patients; pCR was documented in 18 out of 40 patients (45.0%). Grade 3-4 hematological toxicity after NACT occurred in 4 patients; CT/RT associated grade 3 toxicity was found in 7 patients. Early and late postoperative complications were detected in 16, and 11 cases, respectively. Three-year PFS and OS were 66.0% and 86.0%, respectively. CONCLUSIONS:NACT followed by CT/RT by IMRT and RS, is feasible and safe; failure to achieve the primary endpoint has to be recognized; however, enrollment of a higher rate of poor prognosis patients compared to historical data used to calculate sample size, could have resulted in reduced activity. 10.1016/j.ejso.2018.04.019
    Risk of parametrial invasion in women with early stage cervical cancer: a meta-analysis. Ma Congcong,Zhang Yu,Li Rui,Mao Hongluan,Liu Peishu Archives of gynecology and obstetrics PURPOSE:To first evaluate the predictive value of lymph-vascular space invasion (LVSI) and pelvic lymph node metastases (LNM) to parametrial invasion (PI) in patients with early stage cervical cancer. METHODS:A systematic search of electronic databases was conducted to identify publications exploring the association between LVSI, LNM, and PI. The following databases were searched: PubMed/Medline and Web of Science. Twenty relevant studies were included. Pooling of results was done based on these studies and a diagnostic meta-analysis was performed. RESULTS:20 articles and a total of 7373 cases were included in the meta-analysis. 17 studies analyzed the correlation between LVSI and PI and 18 studies evaluated the correlation between LNM and PI. The existence of LVSI accelerated PI with OR being 7.37 (95% CI 5.70-9.54) in fixed-effect model and 7.32 (95% CI 4.65-10.39) in random effects model. LVSI shows high sensitivity of 0.80 and the AUC was 0.82. The existence of LNM accelerated PI. LNM shows the highest specificity of 0.90 and the AUC was 0.77. CONCLUSIONS:Both LVSI and LNM are associated with PI. Conization and lymphadenectomy might be helpful to predict the parametrial status of patients with early stage cervical cancer. In addition, the results of this meta-analysis are helpful for designing further prospective clinical trials. 10.1007/s00404-017-4597-0
    Management of Para-aortic Lymph Node Disease in Patients With Cervical Cancer: What Is the Best Approach? Negrão Marcelo Vailati,Lima Julianne Maria da Silva,Silva Samantha Cabral Severino,Diz Maria Del Pilar Estevez,da Costa Miranda Vanessa International journal of gynecological cancer : official journal of the International Gynecological Cancer Society Cervical cancer remains a prevalent and deadly disease in low-income countries, especially among young and otherwise healthy women. Multimodality treatment has led to a significant improvement in outcomes for patients with locally advanced disease, and this is mainly because of the incorporation of platinum-based chemoradiotherapy in current treatment protocols. However, locally advanced tumors are associated with a greater risk for para-aortic lymph node (PALN) involvement, which is an important adverse prognostic factor. Most staging techniques have low accuracy for detection of disease in this area, which could lead to understaging and undertreatment. Meanwhile, patients with PALN disease are underrepresented in trials addressing the treatment of advanced cervical cancer and a few studies have been directed at this population. The aim of this review is to analyze the current data regarding staging and treatment of cervical cancer with PALN disease to determine which strategy is best when managing these patients. 10.1097/IGC.0000000000000914
    Prognostic Value and Therapeutic Implication of Laparoscopic Extraperitoneal Paraaortic Staging in Locally Advanced Cervical Cancer: A Spanish Multicenter Study. Díaz-Feijoo Berta,Torné Aureli,Tejerizo Álvaro,Benito Virginia,Hernández Alicia,Ruiz Rubén,Domingo Santiago,Luna-Guibourg Rocío,Llueca Antonio,Coronado Pluvio,Gilabert-Estelles Juan,Bebia Vicente,Gil-Ibáñez Blanca,Gil-Moreno Antonio, Annals of surgical oncology PURPOSE:To assess the impact of laparoscopic extraperitoneal paraaortic staging in therapeutic planning and prognosis of patients with locally advanced cervical cancer (LACC) as compared with imaging staging. METHODS:Retrospective multicenter study of stage IB2 and IIA2 to IVA (FIGO 2009) LACC patients who were candidates for primary chemoradiotherapy. The study (surgical) group included 634 patients undergoing laparoscopic/robotic extraperitoneal paraaortic staging treated with extended-field radiotherapy (EFRT) if lymph node involvement was confirmed. The control (imaging) group included 288 patients treated with EFRT when lymph node involvement was suspected on positron emission tomography-computed tomography scans and/or magnetic resonance imaging. RESULTS:In the study group, a median of 13 (range 9-17) lymph nodes were removed, with a rate of positive paraaortic nodes of 18%, with metastatic size ≤ 5 mm in 20.4% of cases. Paraaortic EFRT was administered to 18% of patients in the study group and in 58% of controls. In 34% of patients from the surgical group, EFRT was modified according to surgical findings with respect to imaging staging. The median follow-up in the study and control groups was 3.7 and 4.8 years, respectively. In both groups, the overall survival and cancer-specific disease-free survival were similar. The time interval between diagnosis and starting EFRT was 18 days longer in the study group, without differences in overall survival as compared with controls (hazard ratio 1.00, 95% confidence interval 0.998-1.005; p = 0.307). CONCLUSIONS:Laparoscopic extraperitoneal paraaortic staging in LACC patients is safe and modified therapeutic planning, allowing better selection of candidates for EFRT. 10.1245/s10434-020-08329-5
    Tumour and pelvic lymph node metabolic activity on FDG-PET/CT to stratify patients for para-aortic surgical staging in locally advanced cervical cancer. Martinez A,Voglimacci M,Lusque A,Ducassou A,Gladieff L,Dupuis N,Angeles M A,Martinez C,Tanguy Le Gac Y,Chantalat E,Hitzel A,Courbon F,Ferron G,Gabiache E European journal of nuclear medicine and molecular imaging PURPOSE:The aim of our study was to comprehensively evaluate the most valuable metabolic parameters of cervical tumours and pelvic lymph nodes (PLN) by FDG-PET/CT to predict para-aortic lymph node (PALN) metastasis and stratify patients for surgical staging. METHODS:The study included patients with locally advanced cervical cancer, negative PALN uptake on preoperative FDG-PET/CT, and para-aortic lymphadenectomy. Two senior nuclear medicine physicians expert in gynaecologic oncology reviewed all PET/CT exams, and extracted tumour SUVmax, MTV, and TLG, as well as PLN. Prognostic parameters of PALN involvement were identified using ROC curves and logistic regression analysis. RESULTS:One hundred and twenty-five consecutive locally advanced cervical cancer patients were included. The FDG-PET/CT false-negative rate was, respectively, 27.7% (13/47) and 5.1% (4/78) in patients with and without FDG-PET/CT PLN uptake. The AUC of cervical tumour size, SUVmax, MTV, and TLG was, respectively, 0.75 (0.62-0.87), 0.59 (0.44-0.76), 0.75 (0.60-0.90), and 0.71 (0.56-0.86). The AUC of PLN size, SUVmax, SUVmean, PLN SUVmax/Tumour SUVmax ratio, MTV, and TLG was, respectively, 0.57 (0.37-0.78), 0.82 (0.68-0.95), 0.77 (0.61-0.94), 0.85 (0.72-0.98), 0.69 (0.51-0.87), and 0.74 (0.57-0.91). The metabolic parameter showing the best trade-off between sensitivity and specificity to predict PALN involvement was the ratio between PLN and tumour SUVmax. CONCLUSION:The risk of PALN metastasis in FDG-PET/CT negative PLN patients is very low, so para-aortic lymphadenectomy does not seem justified. In patients with preoperative PLN uptake on FDG-PET/CT, surgical staging led to treatment modification in more than 25% of cases and should therefore be performed. Patients with more than one positive PLN and high PLN metabolic activity are at high risk of para-aortic extension and recurrence. Further prospective evaluation is required to consider intensified treatment modalities without prior PALN dissection. 10.1007/s00259-019-04659-z
    Pretherapeutic staging of locally advanced cervical cancer: Inframesenteric paraaortic lymphadenectomy accuracy to detect paraaortic metastases in comparison with infrarenal paraaortic lymphadenectomy. Azaïs Henri,Ghesquière Louise,Petitnicolas Clothilde,Borghesi Yves,Tresch-Bruneel Emmanuelle,Cordoba Abel,Narducci Fabrice,Bresson Lucie,Leblanc Eric Gynecologic oncology BACKGROUND:Extended-field chemoradiation therapy is usually performed in patients with locally advanced cervical cancer (LACC) and paraaortic (PA) node metastases. Considering the very low rate of skip metastases above inferior mesenteric artery, ilio-inframesenteric paraaortic lymph node dissection (IM-PALND) seems to be an adequate pattern of PALND. Our objective was to assess the accuracy of this management to determine PA nodal status in comparison with infrarenal paraaortic lymphadenectomy (IR-PALND) in case of squamous or glandular cervical cancer. METHODS:All patients with LACC and negative MRI and PET/CT imaging at paraaortic level had laparoscopic staging (followed, if negative, by extraperitoneal paraaortic lymphadenectomy). From January 2011 to September 2015, patients who had IM-PALND were included and were compared to a previous historical series of IR-PALND patients. The two groups differed only at the upper level of dissection. Characteristics of nodal involvement at paraaortic level depending on level of dissection, PET/CT imaging and histology were studied. RESULTS:119 women were included in our study, with 56 patients in the IM-PALND group and 63 in the IR-PALND group. In the IM-PALND group, fewer nodes were resected (p<0.001). There was no difference between the two groups regarding nodal status at paraaortic level (p=0.77). Patterns of nodal involvement were similar whichever the histological subtype of cervical cancer (squamous or glandular). CONCLUSION:IM-PALND appears to be equally effective to assess paraaortic nodal involvement in LACC for both histological subtypes - glandular and squamous carcinomas - and to select patients for extended-field chemoradiation therapy. 10.1016/j.ygyno.2017.09.012
    Patterns of recurrence and prognosis in locally advanced FIGO stage IB2 to IIB cervical cancer: Retrospective multicentre study from the FRANCOGYN group. de Foucher Tiphaine,Bendifallah Sofiane,Ouldamer Lobna,Bricou Alexandre,Lavoue Vincent,Varinot Justine,Canlorbe Geoffroy,Carcopino Xavier,Raimond Emilie,Monnier Laurie,Graesslin Olivier,Touboul Cyril,Collinet Pierre,Neveu Marie-Emmanuelle,Huchon Cyrille,Daraï Emile,Ballester Marcos, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology INTRODUCTION:Evidence-based data describing patterns of recurrence and prognosis in women with FIGO stage IB2 to IIB locally advanced cervical cancer (LACC) are scarce. The purpose of this study was to analyse patterns of recurrence in LACC and their correlation with prognosis, depending on FIGO stage, lymph node (LN) status and treatment modalities. The endpoints of this study were the type of recurrence (locoregional or distant, and time to recurrence), the recurrence free survival, the overall survival and the cumulative incidence for both locoregional and distant recurrence. MATERIALS AND METHODS:Data of women with FIGO stage IB2 to IIB CC treated between April 1996 and May 2016 were retrospectively abstracted from nine French institutions. RESULTS:The median follow-up for the 501 women included was 35.6 months. Recurrences were observed in 158 (31.5%), with a mean time to recurrence of 20.7 months. Women with IIB CC had poorer prognosis, lower 3-year RFS and higher 3-year cumulative incidence of both locoregional and distant recurrences. Women with positive or unknown LN status had poorer prognosis with higher 3-year cumulative incidence of distant recurrence. Women who underwent concomitant chemo-radiotherapy ± vaginal brachytherapy had poorer prognosis, with lower 3-year RFS and higher 3-year cumulative incidence of distant recurrence. CONCLUSIONS:Recurrence location and time to recurrence differ widely depending on the FIGO stage, LN status and treatment modalities, with potential impact on follow-up modalities and therapeutic approaches. 10.1016/j.ejso.2018.11.014
    Validation of the 2018 FIGO cervical cancer staging system. Matsuo Koji,Machida Hiroko,Mandelbaum Rachel S,Konishi Ikuo,Mikami Mikio Gynecologic oncology OBJECTIVE:To validate the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer, with a particular focus on stage IB and stage III disease. METHODS:Two retrospective cohort studies were conducted using The Surveillance, Epidemiology, and End Results Program between 1988 and 2014. The stage IB cohort consisted of node-negative FIGO stage IB1 (tumor size <2 cm), IB2 (2-3.9 cm), and IB3 (≥4 cm) cervical cancer. The stage III cohort consisted of FIGO stage IIIA, IIIB, and stage IIIC1 (any pelvic nodal metastasis) cervical cancer. Multivariable analysis was performed for cause-specific survival based on cancer stage. RESULTS:In the stage IB cohort (n = 8909), stage IB1 tumors were more likely to be adenocarcinoma and low-grade compared to other the groups (P < 0.001). On multivariable analysis, stage IB2 disease was independently associated with a nearly two-fold increased risk of cervical cancer mortality compared to stage IB1 disease (adjusted-hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.62-2.41, P < 0.001). In the stage III cohort (n = 11,733), stage IIIC1 was independently associated with improved cause-specific survival compared to stage IIIB disease (adjusted-HR 0.79, 95%CI 0.74-0.85, P < 0.001). Survival of stage IIIC1 disease significantly differed based on T = stage, (5-year rates: 74.8% for T1, 58.7% for T2, and 39.3% for T3) with a 35.3% difference in absolute survival (P < 0.001). CONCLUSION:The 2018 FIGO staging system for cervical cancer is useful to distinguish survival groups; stage IB1 and stage IB2 disease have distinct characteristics and survival outcomes, while survival in stage IIIC1 varies depending on local tumor factors. 10.1016/j.ygyno.2018.10.026
    Number of Removed Pelvic Lymph Nodes as a Prognostic Marker in FIGO Stage IB1 Cervical Cancer with Negative Lymph Nodes. Wang Rongmin,Tao Xiang,Wu Xiaoyi,Jiang Hongyuan,Xia Hexia Journal of minimally invasive gynecology STUDY OBJECTIVE:To investigate whether the number of removed lymph nodes (RLNs) influences the clinical outcome of stage IB1 cervical cancer on the premise of uniform pelvic lymphadenectomy. DESIGN:Retrospective cohort study. SETTING:Obstetrics and Gynecology Hospital of Fudan University. PATIENTS:Women (n = 782) with stage IB1 cervical cancer. INTERVENTIONS:Laparoscopic radical hysterectomy and uniform pelvic lymphadenectomy (common iliac, external iliac, internal iliac, obturator) for stage IB1 cervical cancer. The median time of follow-up was 64.7 months (range, 4.3-102.8). MEASUREMENTS AND MAIN RESULTS:Of 782 patients with stage IB1 cervical cancer, the median number of pelvic RLNs was 19 (range, 7-49). Twenty-one patients (2.7%) had RLNs ≤ 10, 461 (59.0%) had 11 to 20, 263 (33.6%) had 21 to 30, and 37 (4.7%) had RLNs ≥ 31. The differences were not statistically significant in the clinicopathologic characteristics between the 4 groups (p >.05). In the multivariate analysis, pelvic RLN number became an independent prognostic factor for progression-free survival (PFS) and cancer-specific survival (CSS) in stage IB1 cervical cancer (p = .029; .015 for CSS and PFS). After the stratified analysis by lymph node metastasis, RLN number remained an independent predictive value (p = .026 for CSS, p = .012 for PFS) in patients with negative pelvic lymph nodes. Moreover, patients with RLN number ≤ 10 carried a 5.550-fold higher risk for progression (p <.001) and 5.596-fold greater likelihood of death (p = .001) than those with RLN number > 10 in case of no lymph node metastasis. CONCLUSION:With uniform pelvic lymphadenectomy, the total pelvic RLN number could be a valuable predictor of outcome in stage IB1 cervical cancer without lymph node metastasis during a follow-up of at least 5 years. 10.1016/j.jmig.2019.08.002
    Surgical resection based on ontogenetic cancer field theory for cervical cancer: mature results from a single-centre, prospective, observational, cohort study. Höckel Michael,Wolf Benjamin,Schmidt Katja,Mende Meinhard,Aktas Bahriye,Kimmig Rainer,Dornhöfer Nadja,Horn Lars-Christian The Lancet. Oncology BACKGROUND:Previous findings from our centre suggest that carcinoma of the cervix propagates within ontogenetic cancer fields, tissue compartments defined by staged morphogenesis. We aimed to determine whether surgical treatment that accounts for stage-associated, ontogenetic cancer fields and their associated lymphoid tissues results in locoregional tumour control without the need for adjuvant radiotherapy. METHODS:We did the final clinical and histopathological evaluation of data from, the single-centre, observational, cohort study, the Leipzig School Mesometrial Resection Study. Patients of any age with stage IB1, IB2, IIA1, IIA2, or IIB cervical cancer (according to 2009 International Federation of Gynecology and Obstetrics [FIGO]) had total mesometrial resection or extended mesometrial resection and therapeutic lymph node dissection, done on the basis of ontogenetic cancer fields. We defined sentinel node, first-line, second-line, and third-line lymph node regions as progressive regional cancer fields. Primary outcomes were disease-specific survival and recurrence-free survival, and treatment-related morbidity (assessed with the Franco-Italian glossary). Applying Cox proportional hazard models, ontogenetic local (T) and regional (N) tumour staging was compared with pathological T and N staging. This trial is registered with the German Clinical Trials Register, number DRKS00015171. FINDINGS:Between Oct 16, 1999, and June 27, 2017, 523 patients were treated per protocol and followed up for a median of 61·8 months (IQR 49·3-94·8). In 495 patients with cervical cancer treated with cancer field surgery, 5-year disease-specific survival was 89·4% (95% CI 86·5-92·4) and recurrence-free survival was 83·1% (79·7-86·6). In the per-protocol population of 523 patients, treatment-related morbidity comprised 112 (21%) grade 2 and 15 (3%) grade 3 complications. The most common moderate and severe treatment-related complications and sequelae were wound dehiscence (17 [3%]), hydronephrosis (17 [3%]), bowel obstruction (26 [5%]), and lymph oedema (33 [6%]). One patient (<1%), who received total mesometrial resection, died from postoperative brain infarction. INTERPRETATION:Total or extended mesometrial resection with therapeutic lymph node dissection based on ontogenetic cancer fields results in good survival outcomes of patients with cervical cancer in our institution, but needs to be investigated further in multicentre trials. FUNDING:Leipzig School of Radical Pelvic Surgery, University of Leipzig Medical School, and the Gynecologic Oncology Research Foundation. 10.1016/S1470-2045(19)30389-4
    Prospective multicenter study evaluating the survival of patients with locally advanced cervical cancer undergoing laparoscopic para-aortic lymphadenectomy before chemoradiotherapy in the era of positron emission tomography imaging. Gouy Sebastien,Morice Philippe,Narducci Fabrice,Uzan Catherine,Martinez Alejandra,Rey Annie,Bentivegna Enrica,Pautier Patricia,Deandreis Desiree,Querleu Denis,Haie-Meder Christine,Leblanc Eric Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:The aim of this prospective study conducted in three French comprehensive cancer centers was to evaluate the therapeutic impact on survival of laparoscopic para-aortic (PA) staging surgery in locally advanced cervical cancer (LACC) before chemoradiotherapy. PATIENTS AND METHODS:We conducted a prospective multicenter study of 237 patients treated from 2004 to 2011 for LACC with negative positron emission tomography (PET) imaging of the PA area and undergoing laparoscopic PA lymphadenectomy. Radiation fields were extended to the PA area when PA nodes were involved. Chemoradiotherapy modalities were homogeneous across institutions. Patients with a poor prognosis histologic subtype or peritoneal carcinosis were excluded. RESULTS:Patients had clinical International Federation of Gynecology and Obstetrics stages IB2 (n = 79), IIA (n = 10), IIB (n = 121), III (n = 22), or IVA (n = 5). One hundred ninety-nine patients had squamous carcinoma, and 38 had adenocarcinoma/adenosquamous lesions. Twenty-nine patients (12%) had nodal involvement (false-negative PET-computed tomography [CT] results)-16 with a PA nodal metastasis measuring more than 5 mm and 13 with a nodal metastasis measuring ≤ 5 mm. Event-free survival rates at 3 years in patients without PA involvement or with PA metastasis measuring ≤ or more than 5 mm were 74% (SE, 4%), 69% (SE, 21%), and 17% (SE, 14%; P < .001). CONCLUSION:To our knowledge, this is the largest series of patients reported undergoing such a strategy. We obtained the same survival rate for patients with PA nodal metastasis ≤ 5 mm and patients without PA lymph node involvement, suggesting that this strategy is highly efficient in such patients. Conversely, the survival of patients with PA nodal involvement greater than 5 mm remained poor, despite the absence of extrapelvic disease on PET-CT imaging in this subgroup. 10.1200/JCO.2012.47.3520
    Sensitivity and negative predictive value for sentinel lymph node biopsy in women with early-stage cervical cancer. Salvo Gloria,Ramirez Pedro T,Levenback Charles F,Munsell Mark F,Euscher Elizabeth D,Soliman Pamela T,Frumovitz Michael Gynecologic oncology OBJECTIVE:The role of sentinel lymph node (SLN) biopsy alone for staging of early-stage cervical cancer remains controversial. We aimed to determine the validity of this technique in women with early-stage cervical cancer. METHODS:We retrospectively reviewed women with early-stage cervical cancer who underwent SLN mapping followed by complete pelvic lymphadenectomy as part of initial surgical management from August 1997 through October 2015. All modes of surgical approach were included. Lymphatic mapping was performed using blue dye, technetium-99m sulfur colloid (Tc-99), and/or indocyanine green (ICG). We determined SLN detection rates, sensitivity and negative predictive value. RESULTS:One hundred eighty-eight patients were included, and 35 (19%) had lymph node metastases. At least one SLN was identified in 170 patients (90%), and bilateral SLNs were identified in 117 patients (62%). The majority of SLNs (83%) were found in the pelvis. There was no difference in detection rates between mapping agents, surgical approach, patients with and without prior conization or between patients with tumors <2cm and ≥2cm. The detection rate for bilateral SLNs was significantly lower in women with body mass index (BMI)>30kg/m than in women with lower BMI (p=0.03). Metastatic disease in sentinel nodes was detected by H&E staining in 78% of cases and required ultrastaging/immunohistochemistry in 22% of cases. Only one patient had a false-negative result, yielding a sensitivity of 96.4% (95% CI 79.8%-99.8%) and negative predictive value of 99.3% (95% CI 95.6%-100%). The false-negative rate was 3.6%. CONCLUSIONS:In these women with early-stage cervical cancer, SLN biopsy had very high sensitivity and negative predictive value. We believe it is time to change the standard of care for women with early-stage cervical cancer to SLN biopsy only. 10.1016/j.ygyno.2017.02.005
    SLN mapping in early-stage cervical cancer as a minimal-invasive triaging tool for multimodal treatment. Papadia Andrea,Morosi Chiara,Wang Junjie,Gasparri Maria Luisa,Rau Tilman,Ghezzi Fabio,Mueller Michael D European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology BACKGROUND:To evaluate sensitivity, false negative rate and negative predictive value of the combination of sentinel lymph node (SLN) mapping and frozen section (FS) in triaging cervical cancer patients to a definitive chemo-radiotherapy. METHODS:A retrospective analysis of patients with histologically proven cervical cancer undergoing laparoscopic SLN mapping and frozen section of the SLNs followed by a completion radical hysterectomy, pelvic and/or paraarotic lymphadenectomy. Sensitivity, false negative rate and negative predictive value of the SLN mapping, of the frozen section and of the combination of the two in identifying micro- and macrometastases were calculated. RESULTS:One-hundred and four patients with cervical cancer underwent surgery. Of these, 87 (83.7%) had bilateral detection rates at the SLN mapping and underwent FS evaluation and were selected for statistical analysis. Twenty-five patients had lymph nodal metastases at H&E staining. Of these, 24 displayed metastatic disease to the SLNs and one to a NSLN accounting for a FN rate of 4.0%. Metastases were identified in 21 patients at the FS analysis. Four patients had metastases in the SLNs that were missed at the FS analysis. The FN rate of the FS is 12.5% if we excluded isolated tumour cells in the analysis. The FN rate of the combined methodology (SLN mapping and FS of the SLN) is 16%. Twenty-one out of 25 patients (84.0%) could correctly be triaged to a definitive chemo-radiotherapy. CONCLUSIONS:The combination of SLN mapping and FS of the SLNs is efficient in triaging patients to a definitive chemo-radiotherapy. 10.1016/j.ejso.2019.01.184
    Where Are We Going with Sentinel Lymph Node Mapping in Gynecologic Cancers? Reneé Franklin C,Tanner Edward J Current oncology reports PURPOSE OF REVIEW:Sentinel lymph node (SLN) mapping is a standard of care for lymphatic assessment of many early-stage gynecologic malignancies. We review the current data, emphasizing the utility of SLN mapping in the management of gynecologic cancers. RECENT FINDINGS:Endometrial cancer: recent studies have focused on confirming the safety and efficacy of SLN mapping for high-risk patients. Cervical cancer: the LACC Trial demonstrated reduced survival with minimally invasive surgery, calling into question the validity of prior studies evaluating SLN mapping with a minimally invasive approach. Vulvar cancer: the ongoing GROINS-V-II trial is investigating whether patients with SLN metastasis < 2 mm in diameter can safely undergo adjuvant radiation ± chemotherapy without completion inguinal lymphadenectomy. NCCN guidelines have incorporated SLN mapping as a lymphatic assessment strategy for endometrial, cervical, and vulvar malignancies. SLN mapping appears to reduce morbidity while still maintaining an appropriate detection rate of lymphatic metastasis. Additional clinical trials will further our knowledge of these procedures. 10.1007/s11912-018-0744-4
    Feasibility of radical hysterectomy in women with FIGO stage IIB cervical cancer: an observation study of 10-year experience in a tertiary center. Yuan Lei,Guo Jiaqi,Zhang Xiaochun,Chen Mo,Xu Congjian,Yao Liangqing OncoTargets and therapy Purpose:Although definitive chemoradiotherapy is considered as a standard of care for FIGO stage IIB cervical cancer in many countries, the role of surgery remains controversial. We aimed to evaluate the feasibility and outcomes of patients with FIGO stage IIB cervical cancer who received radical surgery in China. Patients and methods:A total of 74 women with FIGO stage IIB cervical cancer were treated with radical hysterectomy, with or without adjuvant radio/chemoradiotherapy, at the Obstetrics and Gynecology Hospital of Fudan University between 2004 and 2015. Medical charts and clinical data were retrospectively reviewed. The Kaplan-Meier method and Cox regression models were used for survival analyses. In addition, prognostic nomograms predicting overall survival (OS) and progression-free survival (PFS) were constructed. Results:Pathological parametrial involvement (PMI) was only identified in 28.3% (21/74) of all patients and 47.3% (9/19) of patients without neoadjuvant treatment. Major surgical complications, including bladder fistula, intestinal obstruction and ureteral injury, were found in 6.8% (5/74) of patients. Although the use of imaging technologies including magnetic resonance imaging (MRI)/positron emission tomography-computed tomography (PET-CT) has increased after 2010 compared to that prior to 2010, the accuracy of MRI/PET-CT in detecting pathological PMI was lower than that of physical examination under anesthesia (<0.05). Neoadjuvant treatment was the only risk factor affecting the accuracy of pre- and postoperative accordance of PMI (OR: 3.283 [95% CI: 1.363-7.908], =0.008). The 2- and 5-year OS rates were 84.1% and 68.9%, respectively, while the 2- and 5-year cumulative recurrence rates were 26.9% and 39.9%, respectively. Cox regression analyses indicated that pre- and postoperative accordance of PMI, common iliac lymph node metastasis and major surgical complications were significant prognostic factors for both OS and PFS. Conclusion:Radical hysterectomy might be a feasible alternative for FIGO stage IIB cervical cancer. As pre- and postoperative accordance of PMI is relatively low, strategies to appropriately select patients who will benefit from surgery via pretreatment evaluation need to be further investigated. 10.2147/OTT.S173208
    Survival effect of laparoscopic para-aortic staging in locally advanced cervical cancer: a retrospective cohort analysis. Pomel C,Martinez A,Bourgin C,Beguinot M,Benoit C,Naik R,Dauplat J,Lebouedec G,Ferron G BJOG : an international journal of obstetrics and gynaecology OBJECTIVE:This study compares two methods of evaluating para-aortic node involvement in locally advanced cervical cancer (LACC) in order to define external radiotherapy treatment fields: laparoscopic surgical para-aortic lymphadenectomy or PET-CT imaging. POPULATION:We selected 187 patients with LACC who had been treated by chemoradiation therapy in two comprehensive cancer centres from January 2001 to December 2013. A total of 98 underwent para-aortic evaluation by PET-CT (Centre 1) and 89 received surgical laparoscopic excision (Centre 2). METHODS:All patients with LACC were retrospectively collected in each centre. OS and DFS were calculated using the Kaplan-Meier's method and survival curves were compared using log-rank test. MAIN OUTCOME MEASURES:Outcomes were the comparison of patients' disease-free (DFS) and overall survival (OS) between the two centres. RESULTS:Patients had a significantly better disease-free survival in cohort 1 than in cohort 2, at 2 years [80.9% (71.7-87.5) versus 57.1% (46.1-67.3)] and at 5 years [70.5% (58.8-79.9) versus 49.2% (38.2-60.4)] (P = 0.009). These results are confirmed by multivariate analysis model [hazard ratio (HR) 1.93; 95% CI 1.03-3.61; P = 0.04]. The overall survival was also better in cohort 1, both at 2 and 5 years [93.5% (86.5-97.0) versus 78.5% (68.5-86.0) and 85.1% (73.2-92.2) versus 63.8% (51.9-74.2), respectively; P = 0.006]. The multivariate analysis model found concordant results with an increased relative risk of death for patients treated in cohort 2 (HR 2.55; 95% CI 1.09-5.99; P = 0.01). CONCLUSION:In this retrospective cohort analysis, para-aortic surgical staging in LACC is more deleterious for patients than is radiological staging in terms of OS and DFS. TWEETABLE ABSTRACT:Para-aortic surgical staging in LACC is more deleterious for patients than clinical staging. 10.1111/1471-0528.14492
    Lack of Survival Benefit of Para-Aortic Lymphadenectomy in Advanced Cervical Cancer. Gonzalez-Benitez Cristina,Salas Patricia,Grabowski Jacek P,Hernandez Alicia,De Santiago Javier,Zapardiel Ignacio Gynecologic and obstetric investigation INTRODUCTION:The presence of positive para-aortic lymph nodes in advanced cervical cancer remains the most important prognostic factor for survival and also defines the treatment. Our aim was to define the influence of staging para-aortic lymphadenectomy in patients' survival. MATERIAL AND METHODS:The medical records of 74 patients with advanced cervical cancer (FIGO IIB-IVA) were reviewed. In 31 patients (41.9%), the assessment of lymph nodes was performed with imaging test (group 1) and in 43 (58.1%) within a surgical staging para-aortic lymphadenectomy (group 2). We compared both groups according to stage of disease, treatment, progression-free survival (PFS), and overall survival (OS). RESULTS:The extended-field radiotherapy was performed in 44.2 and 19.4% of patients in surgical and imaging staging group, respectively (p = 0.045). The disease-free survival rate was 17.4 ± 17.4 months in group 1 and 14.4 ± 12.6 months in group 2 (p = 0.456). No differences in OS were found between these 2 groups (p = 0.676). CONCLUSIONS:Despite the higher diagnostic accuracy of surgical staging and the higher number of patient who received extended field radiotherapy, we did not find differences between the overall and PFS rates in both the studied groups. Further prospective study on a higher number of patients would be necessary. 10.1159/000497350
    Para-aortic plus pelvic lymphadenectomy in locally advanced cervical cancer: A single institutional experience. Mezquita Gonzalo,Muruzabal Juan Carlos,Perez Beatriz,Aguirre Sara,Villafranca Elena,Jurado Matias European journal of obstetrics, gynecology, and reproductive biology OBJECTIVE:The aim of the study is to assess the safety and efficacy of transperitoneal laparoscopic para-aortic and pelvic lymphadenectomy in the setting of surgical staging of patients with locally advanced cervical cancer (LACC), and to analyse the prognostic value and impact of this staging on the survival prognosis of this condition. STUDY DESIGN:Data from 67 patients with LACC who underwent transperitoneal laparoscopic para-aortic and pelvic lymphadenectomy and who received chemo-radiation therapy were retrospectively analysed. RESULTS:Metastatic lymph nodes (LN) were identified in 32 patients (47.7%), 20 (29.8%) had metastatic LN in the pelvic area and 12 (17.9%) had metastatic LN in the pelvic and para-aortic area. There were no skip metastases in the para-aortic area. After a median follow-up of 54.6 months (5-122.2 months), the 5-year local control and disease-free survival (DFS) rates for the whole group were 91.1% and 60.5% respectively. The five-year DFS for patients without LN metastasis was 86.4%, while for patients with pelvic LN metastases or pelvic and para-aortic metastases was 34.2% and 24.2% respectively (p < 0.001). The five-year overall survival (OS) for the whole group was 67.3%. The mortality rate in patients with para-aortic nodal metastases was increased compared to patients with negative nodes (5-year OS 21.3% vs 81.6% respectively, p = 0.005), but the OS rate was similar in patients with negative nodes and those with only pelvic nodes affected (5-year OS 81.6% vs 70.8% respectively, p = 0.380). This approach allowed the modification of the initial treatment plan in the para-aortic area in 13.4% of patients and in the pelvic area in 28.3%. The overall intraoperative morbidity rate was 5.9%, while the postoperative morbidity rate was 10.4%, with only 3 patients presenting grade 3 morbidity. CONCLUSIONS:Transperitoneal para-aortic and pelvic lymphadenectomy provides precise information about nodal state and allows personalized treatment planning in patients with LACC, avoiding false negative (FN) and false positive (FP) imaging results. In 17.9% of patients, the external beam radiotherapy (EBRT) field had to include the aortic area, whilst 47.7% received pelvic boost to the involved nodes. 10.1016/j.ejogrb.2019.02.033
    Accessory polar renal artery not pre-operatively visualized at extra-peritoneal para-aortic lymphadenectomy. Madsen Melisa,Gorostidi Mikel,Ruiz Ruben,Jaunarena Ibon,Cobas Paloma,Lekuona Arantza International journal of gynecological cancer : official journal of the International Gynecological Cancer Society The objective of this video is to describe the technique of extra-peritoneal para-aortic laparoscopic lymphadenectomy and emphasize potential vascular risks that should be taken into account during the procedure.The procedure was performed at Donostia University Hospital, a tertiary referral and educational center in San Sebastián, Spain.A 58-year-old woman, body mass index 25.4 kg/m, G2P2, with a diagnosis of intermediate-risk endometrial adenocarcinoma, International Federation of Gynecology and Obstetrics (FIGO) IBG2 based on pre-operative endometrial histology and pre-operative magnetic resonance imaging (MRI), but upstaged to high-risk endometrial adenocarcinoma on final report (IBG3). In our hospital, risk stratification is based on pelvic MRI (myometrial invasion, cervical invasion) and biopsy (histology and grade) to tailor surgery. Computed tomography (CT) scan pre-operatively is only performed for type 2 endometrial carcinoma and grade 3 histologies.The local institutional review board was consulted, which confirmed that the study was exempt from requiring approval.The patient underwent an extra-peritoneal para-aortic laparoscopic lymphadenectomy, trans-peritoneal bilateral pelvic lymphadenectomy, and a total hysterectomy and bilateral salpingo-oophorectomy.It is mandatory to check pre-operative imaging studies in order to identify vascular anomalies that are not uncommon and may increase the risk of vascular complications.1 Frequently these vascular anomalies, such as a retro-aortic left renal vein, or a double vena cava or left vena cava, may be a casual finding in the pre-operative study, and often such findings are not reported by the radiologist. It is vitally important that the surgeon checks for and identifies any such anomolies, as the risk of complications may be decreased if anomalies of this type are detected pre-operatively.In addition, in the case of existing polar renal arteries, these are frequently not identified in the pre-operative study,2 leading to a risk of injury and partial renal necrosis. There are several anatomical variations of the renal arteries, with an aortic lower polar artery found in 3% of cadavers and 1% of patients on CT, more frequently on the right side.3 Renovascular hypertension4 secondary to an injury of an accessory polar renal artery (APRA) has also been described.Although vascular anomalies, especially venous ones, are more frequently found at the infra-renal left level, in this video we show access to the right side of the dissection and the care that needs to be taken in order not to damage a vascular structure at this level. Special caution is required with the right side of the dissection so as not to injure any perforating veins, including Fellow's vein, when pushing all the nodes to the roof of the dissection.The dissection maneuvers are fine and blunt, establishing bridges of tissue to be sectioned, and thus identifying vascular structures, such as a right APRA that is to be identified and preserved.The surgeon must have a good knowledge of retro-peritoneal vascular anatomy, they should examine pre-operative imaging studies to check for vascular anomalies, and they need to possess an accurate surgical technique to avoid potential vascular injury during laparoscopic para-aortic lymphadenectomy. 10.1136/ijgc-2019-000383
    Extent of lymphovascular space invasion may predict lymph node metastasis in uterine serous carcinoma. Qian Yushen,Pollom Erqi L,Nwachukwu Chika,Seiger Kira,von Eyben Rie,Folkins Ann K,Kidd Elizabeth A Gynecologic oncology OBJECTIVES:Emerging evidence suggests that extent of lymphovascular space invasion (LVSI) predicts for risk of lymph node metastasis in endometrioid uterine cancers. However, this correlation remains unknown in the setting of uterine serous carcinoma (USC). We sought to examine the association between extent of LVSI and other histopathologic characteristics with risk of nodal metastasis for women with USC. MATERIALS/METHODS:Pathological data from all cases of uterine serous carcinoma between July 1998 to July 2015 at our institution were reviewed. Descriptive, univariate, and multivariate logistic regression analysis of selected pathologic features were performed. RESULTS:88 patients with USC underwent total abdominal or laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and selective lymphadenectomy. Surgical staging revealed the following FIGO stage distributions: I (41%), II (8%), III (32%), IV (19%). LVSI was present in 44 (50%) patients. 36 patients (41%) had LN metastases with median number of total nodes removed of 17 (range, 1-49). On univariate analysis, depth of myometrial invasion, LVSI, tumor size, and cervical stromal involvement were significantly associated with nodal involvement. In a multivariate model, LVSI (OR 6.25, 95% CI 2.2-18.0, p<0.01) and cervical stromal involvement (OR 3.33, 95% CI 1.10-10.0, p=0.03) were the only factors that remained significant. Among patients with LVSI-positive disease, extensive LVSI was associated with increased risk of nodal involvement compared to focal LVSI (90% vs 29%, p=0.04). CONCLUSIONS:Presence and extent of LVSI, and cervical stromal invasion are important predictors for lymph node metastasis in uterine serous carcinoma. 10.1016/j.ygyno.2017.07.119
    Comparison of lymphatic complications between sentinel node navigation surgery and pelvic lymphadenectomy in patients with cervical cancer. Togami Shinichi,Kubo Rintaro,Kawamura Toshihiko,Yanazume Shintaro,Kamio Masaki,Kobayashi Hiroaki Japanese journal of clinical oncology BACKGROUND:Sentinel node navigation surgery (SNNS) has been frequently used in early cervical cancer. However, the incidence and potential reduction of lymphatic complications following the removal of the sentinel lymph node remain unknown. Thus, this study aimed to evaluate the occurrence of lymphatic complications post sentinel node navigation surgery in patients with early cervical cancer. METHODS:A total of 167 patients, including 70 and 97 patients who had undergone SNNS and pelvic lymphadenectomy (PLA), respectively, were enrolled in this study. We compared the lymphatic complications (lower extremity lymphedema and pelvic lymphocele) between the SNNS and PLA groups. RESULTS:The median number of sentinel lymph nodes removed was 2 (range: 1-14). Among the 70 patients in the SNNS group, there were 0 (0%) and 3 (4.3%) occurrences of lower extremity lymphedema and pelvic lymphocele, respectively. The occurrences of lower extremity lymphedema and pelvic lymphocele were significantly lower in the SNNS group than in the PLA group, despite circumflex iliac node removal. CONCLUSIONS:The occurrence of lymphatic complications (lower extremity lymphedema and pelvic lymphocele) was significantly lower in the SNNS group than in the PLA group. We found that SNNS, and not PLA, was the best treatment option for preventing the development of lower extremity lymphedema and pelvic lymphocele, despite circumflex iliac node preservation. 10.1093/jjco/hyaa001
    Risk factors for lymphatic complications following lymphadenectomy in patients with cervical cancer. Togami Shinichi,Kawamura Toshihiko,Fukuda Mika,Yanazume Shintaro,Kamio Masaki,Kobayashi Hiroaki Japanese journal of clinical oncology Background:The purpose of this study was to evaluate the occurrence of lymphatic complications following pelvic lymphadenectomy (PLA) in patients with cervical cancer. Methods:A retrospective study of 169 cervical cancer patients was conducted. Lower extremity lymphedema (LEL) was diagnosed using the International Society of Lymphology guidelines, and pelvic lymphocele (PL) was evaluated using trans-vaginal ultrasonography and computed tomography. Results:The median patient age was 46 years (range: 22-74) and median body mass index was 21.7 kg/m2 (range: 15.7-37.1). The median number of lymph nodes (LNs) removed was 27 (range: 22-74); 94 (55.6%) patients underwent circumflex iliac node (CIN) dissection; 39 (23.1%) patients received adjuvant chemotherapy; and 81 (47.9%) patients received adjuvant postoperative radiotherapy. There were 28 (16.6%) and 32 (18.9%) occurrences of LEL and PL, respectively. In multivariate logistic regression analysis, the number of LNs removed (odds ratio [OR]: 3.37; 95% CI: 1.43-8.54; P = 0.0053) and CIN removal (OR: 3.92; 95% CI: 1.55-11.4; P = 0.0033) were independent risk factors for LEL; however, no risk factors were significantly associated with PL. Conclusions:Our results demonstrated that CIN removal and the number of LNs removed were significant risk factors for LEL in patients with cervical cancer. However, we did not identify any significant risk factors for PL in this study. We instead speculate that LN dissection itself causes PL. We suggest that establishment of comprehensive PLA without CIN dissection, or use of the sentinel lymph node concept, will prevent the occurrence of lymphatic complications in cervical cancer patients. 10.1093/jjco/hyy151
    The role of pelvic lymphocele in the development of early postoperative complications. Neagoe Octavian Constantin,Ionica Mihaela,Mazilu Octavian Medicine With the increasing incidence of gynecologic malignancy, radical hysterectomy represents an important part of the adequate treatment of these patients. The pelvic lymphocele is a known side effect of pelvic and para-aortic lymphadenectomy. The aim of our study was to assess the role of the lymphocele in the development of early postoperative complications.A single-center, retrospective analysis between January 2000 and May 2017 revealed 1867 patients with cervical and endometrial cancer, treated through radical or modified radical hysterectomy and pelvic lymphadenectomy. Postoperative complications and the occurrence of pelvic lymphocele were evaluated.Approximately 47.6% of patients were diagnosed with pelvic lymphocele, with only 5.2% being symptomatic. Early postoperative complications rate recorded an incidence of 8.1%, occurring more frequent if lymphocele were present (P < .001). The pelvic lymphocele represented, in univariate analysis, a risk factor for the development of pelvic abscesses, but not for deep vein thrombosis, lymphedema, or bowel obstruction. Hydronephrosis was found to be significantly correlated with the pelvic lymphocele, but we believe this urological complication to have a different underlining mechanism. Neoadjuvant radiotherapy represented in both uni- and multivariate analysis a risk factor for the occurrence of postoperative complications.In the postoperative context of oncogynecological surgery, pelvic lymphocele occur at high rates, representing a statistical risk factor for hydronephrosis and pelvic abscesses, with neoadjuvant radiotherapy being an independent risk factor for early postoperative complications. 10.1097/MD.0000000000012353
    Radiation Therapy for Para-Aortic Lymph Node Metastasis from Uterine Cervical Cancer. Hata Masaharu,Miyagi Etsuko,Koike Izumi,Numazaki Reiko,Asai-Sato Mikiko,Kasuya Takeo,Kaizu Hisashi,Mukai Yuki,Hirahara Fumiki,Inoue Tomio Anticancer research AIM:To evaluate the efficacy of radiation therapy for para-aortic lymph node metastases from uterine cervical cancer and to identify an optimal radiation regimen. PATIENTS AND METHODS:A total of 80 metastatic para-aortic lymph nodes, ranging from 11-50 mm (median=20 mm) on computed tomography, in 22 patients with squamous cell carcinoma of the uterine cervix were initially treated with radiation therapy. Total radiation doses for para-aortic lymph node metastases were 40-61.2 Gy (median=50.4 Gy) in 1.8-2 Gy fractions. RESULTS:Eight out of the 22 patients remained alive at a median follow-up of 32 months. Seven irradiated lymph nodes, 20-50 mm in diameter, in four patients progressed after irradiation at total doses of 44-50.4 Gy. No metastatic lymph nodes administered >50.4 Gy (median=55.8 Gy) exhibited progression after irradiation. All metastatic lymph nodes ≤ 25 mm in diameter irradiated with 50 or 50.4 Gy were controlled. The 3-year lymph node progression-free rates were 78% in the cohort of 22 patients and 89% considering all 80 metastatic lymph nodes. Apart from transient hematological reactions, two patients developed grade 3 or more therapy-related toxicities, including radiation proctitis in one and hemorrhagic cystitis and colitis in another. CONCLUSION:Radiation therapy can effectively control para-aortic lymph node metastases in patients with uterine cervical cancer. A total dose of 50.4 Gy in 1.8 Gy fractions is sufficient to control metastatic lymph nodes ≤ 25 mm in diameter, whereas a higher dose (approximately 55.8 Gy) may be required for larger nodes.
    Survival after a nationwide adoption of robotic minimally invasive surgery for early-stage cervical cancer - A population-based study. Jensen Pernille T,Schnack Tine H,Frøding Ligita P,Bjørn Signe F,Lajer Henrik,Markauskas Algirdas,Jochumsen Kirsten M,Fuglsang Katrine,Dinesen Jacob,Søgaard Charlotte H,Søgaard-Andersen Erik,Jensen Marianne M,Knudsen Aage,Øster Laura H,Høgdall Claus European journal of cancer (Oxford, England : 1990) AIM:Lately, the safety of minimally invasive surgery (MIS) in the treatment of cervical cancer (CC) has been questioned. This study aimed to evaluate the risk of recurrence and survival after a nationwide adoption of robotic MIS for the treatment of early-stage CC in Denmark. METHODS:Population-based data on all Danish women with early-stage CC, who underwent radical hysterectomy January 1st 2005-June 30th 2017 were retrieved from the Danish Gynecologic Cancer Database and enriched with follow-up data on recurrence, death and cause of death. The cohort was divided into two groups according to the year of robotic MIS introduction at each cancer centre. Chi-squared or Fischer test, the Kaplan Meier method and multivariate Cox regression were used for comparison between groups. RESULTS:One thousand one hundred twenty-five patients with CC were included; 530 underwent surgery before (group 1) and 595 underwent surgery after (group 2) the introduction of robotic MIS. The 5-year rate of recurrence was low: 8.2% and 6.3% (p = 0.55) in group 1 and 2, respectively. In adjusted analyses, this corresponded to a five-year disease-free survival, hazard ratio (HR) 1.23 [95% confidence interval (CI) 0.79-1.93]. No difference in site of recurrence (P = 0.19) was observed. The cumulative cancer-specific survival was 94.1% and 95.9% (P = 0.10) in group 1 and 2, respectively, corresponding to a HR 0.60 [95% CI 0.32-1.11] in adjusted analyses. CONCLUSION:In this population-based cohort study, the Danish nationwide adoption of robotic MIS for early-stage CC was not associated with increased risk of recurrence or reduction in survival outcomes. 10.1016/j.ejca.2019.12.020
    Quality of life in patients with cervical cancer after open versus minimally invasive radical hysterectomy (LACC): a secondary outcome of a multicentre, randomised, open-label, phase 3, non-inferiority trial. Frumovitz Michael,Obermair Andreas,Coleman Robert L,Pareja Rene,Lopez Aldo,Ribero Reitan,Isla David,Rendon Gabriel,Bernardini Marcus Q,Buda Alessandro,Moretti-Marquez Renato,Zevallos Albert,Vieira Marcelo A,Zhu Tao,Land Russell P,Nicklin James,Asher Rebecca,Robledo Kristy P,Gebski Val,Ramirez Pedro T The Lancet. Oncology BACKGROUND:In the phase 3 LACC trial and a subsequent population-level review, minimally invasive radical hysterectomy was shown to be associated with worse disease-free survival and higher recurrence rates than was open radical hysterectomy in patients with early stage cervical cancer. Here, we report the results of a secondary endpoint, quality of life, of the LACC trial. METHODS:The LACC trial was a randomised, open-label, phase 3, non-inferiority trial done in 33 centres worldwide. Eligible participants were women aged 18 years or older with International Federation of Gynaecology and Obstetrics (FIGO) stage IA1 with lymphovascular space invasion, IA2, or IB1 adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma of the cervix, with an Eastern Cooperative Oncology Group performance status of 0 or 1, who were scheduled to have a type 2 or 3 radical hysterectomy. Participants were randomly assigned (1:1) to receive open or minimally invasive radical hysterectomy. Randomisation was done centrally using a computerised minimisation program, stratified by centre, disease stage according to FIGO guidelines, and age. Neither participants nor investigators were masked to treatment allocation. The primary endpoint of the LACC trial was disease-free survival at 4·5 years, and quality of life was a secondary endpoint. Eligible patients completed validated quality-of-life and symptom assessments (12-item Short Form Health Survey [SF-12], Functional Assessment of Cancer Therapy-Cervical [FACT-Cx], EuroQoL-5D [EQ-5D], and MD Anderson Symptom Inventory [MDASI]) before surgery and at 1 and 6 weeks and 3 and 6 months after surgery (FACT-Cx was also completed at additional timepoints up to 54 months after surgery). Differences in quality of life over time between treatment groups were assessed in the modified intention-to-treat population, which included all patients who had surgery and completed at least one baseline (pretreatment) and one follow-up (at any timepoint after surgery) questionnaire, using generalised estimating equations. The LACC trial is registered with ClinicalTrials.gov, NCT00614211. FINDINGS:Between Jan 31, 2008, and June 22, 2017, 631 patients were enrolled; 312 assigned to the open surgery group and 319 assigned to the minimally invasive surgery group. 496 (79%) of 631 patients had surgery completed at least one baseline and one follow-up quality-of-life survey and were included in the modified intention-to-treat analysis (244 [78%] of 312 patients in the open surgery group and 252 [79%] of 319 participants in the minimally invasive surgery group). Median follow-up was 3·0 years (IQR 1·7-4·5). At baseline, no differences in the mean FACT-Cx total score were identified between the open surgery (129·3 [SD 18·8]) and minimally invasive surgery groups (129·8 [19·8]). No differences in mean FACT-Cx total scores were identified between the groups 6 weeks after surgery (128·7 [SD 19·9] in the open surgery group vs 130·0 [19·8] in the minimally invasive surgery group) or 3 months after surgery (132·0 [21·7] vs 133·0 [22·1]). INTERPRETATION:Since recurrence rates are higher and disease-free survival is lower for minimally invasive radical hysterectomy than for open surgery, and postoperative quality of life is similar between the treatment groups, gynaecological oncologists should recommend open radical hysterectomy for patients with early stage cervical cancer. FUNDING:MD Anderson Cancer Center and Medtronic. 10.1016/S1470-2045(20)30081-4
    Survival after Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer. Melamed Alexander,Margul Daniel J,Chen Ling,Keating Nancy L,Del Carmen Marcela G,Yang Junhua,Seagle Brandon-Luke L,Alexander Amy,Barber Emma L,Rice Laurel W,Wright Jason D,Kocherginsky Masha,Shahabi Shohreh,Rauh-Hain J Alejandro The New England journal of medicine BACKGROUND:Minimally invasive surgery was adopted as an alternative to laparotomy (open surgery) for radical hysterectomy in patients with early-stage cervical cancer before high-quality evidence regarding its effect on survival was available. We sought to determine the effect of minimally invasive surgery on all-cause mortality among women undergoing radical hysterectomy for cervical cancer. METHODS:We performed a cohort study involving women who underwent radical hysterectomy for stage IA2 or IB1 cervical cancer during the 2010-2013 period at Commission on Cancer-accredited hospitals in the United States. The study used inverse probability of treatment propensity-score weighting. We also conducted an interrupted time-series analysis involving women who underwent radical hysterectomy for cervical cancer during the 2000-2010 period, using the Surveillance, Epidemiology, and End Results program database. RESULTS:In the primary analysis, 1225 of 2461 women (49.8%) underwent minimally invasive surgery. Women treated with minimally invasive surgery were more often white, privately insured, and from ZIP Codes with higher socioeconomic status, had smaller, lower-grade tumors, and were more likely to have received a diagnosis later in the study period than women who underwent open surgery. Over a median follow-up of 45 months, the 4-year mortality was 9.1% among women who underwent minimally invasive surgery and 5.3% among those who underwent open surgery (hazard ratio, 1.65; 95% confidence interval [CI], 1.22 to 2.22; P=0.002 by the log-rank test). Before the adoption of minimally invasive radical hysterectomy (i.e., in the 2000-2006 period), the 4-year relative survival rate among women who underwent radical hysterectomy for cervical cancer remained stable (annual percentage change, 0.3%; 95% CI, -0.1 to 0.6). The adoption of minimally invasive surgery coincided with a decline in the 4-year relative survival rate of 0.8% (95% CI, 0.3 to 1.4) per year after 2006 (P=0.01 for change of trend). CONCLUSIONS:In an epidemiologic study, minimally invasive radical hysterectomy was associated with shorter overall survival than open surgery among women with stage IA2 or IB1 cervical carcinoma. (Funded by the National Cancer Institute and others.). 10.1056/NEJMoa1804923
    Surgical and Pathological Outcomes of Laparoscopic Versus Abdominal Radical Hysterectomy With Pelvic Lymphadenectomy and/or Para-aortic Lymph Node Sampling for Bulky Early-Stage Cervical Cancer. Zhu Tao,Chen Xi,Zhu Jianqing,Chen Yaqing,Yu Aijun,Chen Lu,Shou Huafeng,Wu Meijuan,Zhang Ping International journal of gynecological cancer : official journal of the International Gynecological Cancer Society BACKGROUND AND OBJECTIVES:The aim of this study was to compare the feasibility, morbidity, and recurrence rate of total laparoscopic radical hysterectomy (LRH) with those of abdominal radical hysterectomy (ARH) for bulky early-stage cervical cancer. METHODS:We performed a retrospective cohort study of 112 patients with stage IB1 or IIA2 cervical cancer in which the tumor diameter was 3 cm or greater. All patients underwent LRH (n = 30) or ARH (n = 82) with pelvic lymphadenectomy and/or para-aortic lymph node sampling between May 2011 and November 2014. Perioperative outcomes were compared between the 2 surgical groups. RESULTS:The laparoscopic approach consisted of 4 trocar insertions. Age, tumor diameter, and pelvic lymph nodes significantly differed between the 2 cohorts. Body mass index, International Federation of Gynecology and Obstetrics stage, histologic type and grade, deep stromal invasion, lymphovascular space invasion, positive margins, and adjuvant therapy were not significantly different between the 2 cohorts. Laparoscopic radical hysterectomy exhibited favorable results compared with ARH in terms of operating time, blood loss, intestinal exhaust time, and length of hospital stay. In addition, recurrence was observed in 5 LRH patients (16.7%) and 9 ARH patients (11.7%). CONCLUSIONS:The surgical outcomes of LRH with pelvic lymphadenectomy and/or para-aortic lymph node sampling exhibited a similar therapeutic efficacy to those of the ARH approach. 10.1097/IGC.0000000000000716
    Short-term outcomes of robotic-assisted versus conventional laparoscopic radical hysterectomy for early-stage cervical cancer: A single-center study. Oyama Keisuke,Kanno Kiyoshi,Kojima Ryuji,Shirane Akira,Yanai Shiori,Ota Yoshiaki,Andou Masaaki The journal of obstetrics and gynaecology research AIM:Our hospital adopted laparoscopic surgery for early-stage cervical cancer in August 1998, with robot-assisted surgery implemented in October 2013. This study aimed to compare short-term outcomes for conventional laparoscopic radical hysterectomy (LRH) and robot-assisted radical hysterectomy (RARH) and assess the technical feasibility of RARH for early-stage cervical cancer. METHODS:We retrospectively compared operative time, blood loss, number of resected lymph nodes, length of postoperative hospital stay, rate of positive vaginal margin and perioperative complications between two groups of 121 patients (LRH group, n = 57; RARH group, n = 64) with stage IA2 to IIB, among 164 patients who underwent endoscopic radical hysterectomy for early-stage cervical cancer performed between January 2010 and December 2017 by an expert surgeon, excluding cases of para-aortic lymphadenectomy. RESULTS:No differences in patient background, in terms of age and body mass index, were identified. For the LRH/RARH groups (mean ± standard deviation), results obtained were as follows: operative time, 211 ± 38/280 ± 59 min (P < 0.01); blood loss, 219 ± 114/370 ± 231 mL (P < 0.01); number of resected lymph nodes, 38.5 ± 15.9/50.2 ± 18.2 (P < 0.01); length of postoperative hospital stay, 11.6 ± 3.3/11.3 ± 4.8 days (P = 0.67); and perioperative complications with Clavien-Dindo classification of grade III or higher, 1.8/7.8% (P = 0.13). CONCLUSION:The operative time was significantly longer and blood loss greater in the RARH than LRH group. A greater number of lymph nodes were removed in the RARH group. However, these differences seem to be within a clinically acceptable range, showing that RARH is as feasible and safe as LRH in terms of short-term outcomes. 10.1111/jog.13858
    Comparison of laparoscopic versus open radical hysterectomy in patients with early-stage cervical cancer: a multicenter study in China. Hu Ting Wen Yi,Huang Yue,Li Na,Nie Dan,Li Zhengyu International journal of gynecological cancer : official journal of the International Gynecological Cancer Society INTRODUCTION:Recently, the safety of minimally invasive surgery in the treatment of cervical cancer has been questioned. This study was designed to compare the disease-free survival and overall survival of abdominal radical hysterectomy and laparoscopic radical hysterectomy in patients with early-stage cervical cancer. METHODS:A total of 1065 patients with early-stage cervical cancer who had undergone abdominal/laparoscopic radical hysterectomy between January 2013 and December 2016 in seven hospitals were retrospectively analyzed. The 1:1 propensity score matching was performed in all patients. Patients with tumor size ≥2 cm and <2 cm were stratified and analyzed separately. Disease-free survival and overall survival were compared between matched groups. After confirming the normality by the Shapiro-Wilks test, the Mann-Whitney U test and the χ test were used for the comparison of continuous and categorical variables, respectively. The survival curves were generated by the Kaplan-Meier method and compared by log-rank test. RESULTS:After matching, a total of 812 patients were included in the disease-free survival and overall survival analyses. In the entire cohort, the laparoscopic radical hysterectomy group had a significantly shorter disease-free survival (HR 1.65, 95% CI 1.00 to 2.73; p=0.048) but not overall survival (HR 1.60, 95% CI 0.89 to 2.88; p=0.12) when compared with the abdominal radical hysterectomy group. In patients with tumor size ≥2 cm, the laparoscopic radical hysterectomy group had a significantly shorter disease-free survival (HR 1.93, 95% CI 1.05 to 3.55; p=0.032) than the abdominal radical hysterectomy group, whereas no significant difference in overall survival (HR 1.90, 95% CI 0.95 to 3.83; p=0.10) was found. Additionally, in patients with tumor size <2 cm, the laparoscopic radical hysterectomy and abdominal radical hysterectomy groups had similar disease-free survival (HR 0.71, 95% CI 0.24 to 2.16; p=0.59) and overall survival (HR 0.59, 95% CI 0.11 to 3.13; p=0.53). CONCLUSION:Laparoscopic radical hysterectomy was associated with inferior disease-free survival compared with abdominal radical hysterectomy in the entire cohort, as well as in patients with tumor size ≥2 cm. For the surgical treatment of patients with early-stage cervical cancer, priority should be given to open abdominal radical hysterectomy. 10.1136/ijgc-2020-001340
    Recurrence Rates in Patients With Cervical Cancer Treated With Abdominal Versus Minimally Invasive Radical Hysterectomy: A Multi-Institutional Retrospective Review Study. Uppal Shitanshu,Gehrig Paola A,Peng Katherine,Bixel Kristin L,Matsuo Koji,Vetter Monica H,Davidson Brittany A,Cisa M Paige,Lees Brittany F,Brunette Laurie L,Tucker Katherine,Stuart Staley Allison,Gotlieb Walter H,Holloway Robert W,Essel Kathleen G,Holman Laura L,Goldfeld Ester,Olawaiye Alexander,Rose Stephen L Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:To compare the disease-free survival (DFS) between open and minimally invasive radical hysterectomies (RH) performed in academic medical institutions. METHODS:Retrospective multi-institutional review of patients undergoing RH for stage IA1 (with lymphovascular invasion), IA2, and IB1 squamous, adenocarcinoma, or adenosquamous carcinoma between January 1, 2010 and December 31, 2017. RESULTS:Of 815 patients, open RH was performed in 255 cases (29.1%) and minimally invasive RH in 560 cases (70.9%). There were 19 (7.5%) recurrences in the open RH and 51 (9.1%) recurrences in the minimally invasive group ( = .43). Risk-adjusted analysis revealed that minimally invasive RH was independently associated with an increased hazard of recurrence (aHR, 1.88; 95% CI, 1.04 to 3.25). Other factors independently associated with an increased hazard of recurrence included tumor size, grade, and adjuvant radiation. Conization before surgery was associated with lower recurrence risk (aHR, 0.4; 95% CI, 0.23 to 0.71). There was no difference in OS in the unadjusted analysis (HR, 1.14; 95% CI, 0.61 to 2.11) or after risk adjustment (aHR, 1.01; 95% CI, 0.5 to 2.2). Of 264 patients with tumors ≤ 2 cm on final pathology (excluding those with no residual tumor on final pathology), 2/82 (2.4%) recurred in the open RH group and 16/182 (8.8%) in the minimally invasive RH group ( = .058). In propensity score matching analysis, 7/159 (4.4%) recurrences were noted in the open RH group and 18/156 (11.5%) in the minimally invasive RH group ( = .019). Survival analysis revealed an increased risk of recurrence in the minimally invasive group in propensity-matched cohort (HR, 2.83; 95% CI, 1.1 to 7.18). CONCLUSION:In this retrospective series, patients undergoing minimally invasive radical hysterectomy, including those with tumor size ≤ 2 cm on final pathology, had inferior DFS but not overall survival in the entire cohort. 10.1200/JCO.19.03012
    Re: Minimally Invasive Versus Abdominal Radical Hysterectomy for Cervical Cancer. Ohlmann Carsten-Henning,Hadaschik Boris European urology 10.1016/j.eururo.2019.01.029
    Comparative Effectiveness of Abdominal versus Laparoscopic Radical Hysterectomy for Cervical Cancer in the Postdissemination Era. Kim Jin Hee,Kim Kyungjoo,Park Seo Jin,Lee Jung-Yun,Kim Kidong,Lim Myong Cheol,Kim Jae Weon Cancer research and treatment : official journal of Korean Cancer Association PURPOSE:Despite the benefits of minimally invasive surgery for cervical cancer, there are a lack of randomized trials comparing laparoscopic radical hysterectomy and abdominal radical hysterectomy. We compared morbidity, cost of care, and survival between abdominal radical hysterectomy and laparoscopic radical hysterectomy for cervical cancer. Materials and Methods:We used the Korean nationwide database to identify women with cervical cancer who underwent radical hysterectomy from January 1, 2011 to December 31, 2014. Patients who underwent abdominal radical hysterectomy were compared to those who underwent laparoscopic radical hysterectomy. Perioperative morbidity, the use of adjuvant therapy, and survival were evaluated after propensity score balancing. RESULTS:We identified 6,335 patients, including 3,235 who underwent abdominal radical hysterectomy and 3,100 who underwent laparoscopic radical hysterectomy. The use of laparoscopic radical hysterectomy increased from 46.1% in 2011 to 51.8% in 2014. Patients who were younger, had a more recent year of diagnosis, and were treated in the metropolitan area were more likely to undergo a laparoscopic procedure (p < 0.001). Compared to abdominal radical hysterectomy, laparoscopic radical hysterectomy was associated with lower rates of complication, fewertransfusions, a shorter hospital stay, less adjuvant therapy, and reduced total medical costs (p < 0.001). Laparoscopic surgery was associated with a better overall survival than abdominal operation (hazard ratio, 0.74; 95% confidence interval, 0.64 to 0.85). CONCLUSION:In the postdissemination era, laparoscopic radical hysterectomy was associated with more favorable morbidity profiles, a lower cost of care, and comparable survival than abdominal radical hysterectomy. 10.4143/crt.2018.120
    Isolated para-aortic lymph node metastasis in FIGO stage IA2-IB2 carcinoma of the cervix: Revisiting the role of surgical assessment. Del Carmen Marcela G,Pareja Rene,Melamed Alexander,Rodriguez Juliana,Greer Anna,Clark Rachel M,Rice Laurel W Gynecologic oncology OBJECTIVES:To investigate the utility of para-aortic lymph node dissection among women undergoing radical hysterectomy and pelvic lymph adenectomy for FIGO Stage IA2-IB2 cervical cancer using the National Cancer Database (NCDB). METHODS:We identified patients with stage IA2-IB2 squamous cell, adenosquamous, or adenocarcinoma of the cervix diagnosed 2011-2014 in the NCDB. The primary outcome was the negative predictive value of histologically assessed pelvic lymph node status for para-aortic lymph node status among women undergoing pelvic and para-aortic lymph node dissection. We calculated probability of para-aortic lymph node metastasis conditional on pelvic lymph node status. Finally, we compared overall survival between patients undergoing para-aortic lymph node dissection and those in whom this procedure was omitted. RESULTS:A total of 3212 patients met study inclusion criteria, of whom 994 (30.9%) underwent para-aortic lymph node dissection. In this group, the risk of isolated para-aortic metastasis was 0.11%. The negative predictive value of surgically assessed pelvic lymph nodes to predict para-aortic lymph node status was 99.9% (95% CI 99.9-99.9). Among 93 patients with pelvic lymph node metastasis, 18 (19.4%) had concurrent para-aortic lymph node metastasis. There was no difference in overall survival between women undergoing pelvic and para-aortic lymph node dissection compared with those undergoing pelvic lymphadenectomy only (p = 0.69). CONCLUSIONS:In patients undergoing radical hysterectomy and pelvic lymphadenectomy for stage IA2-IB2 cervical cancer, para-aortic lymph node dissection is not warranted based on the low risk of isolated metastatic disease, and lack of survival benefit associated with the procedure. 10.1016/j.ygyno.2018.07.010
    The Significance of Para-Aortic Nodal Size and the Role of Adjuvant Systemic Chemotherapy in Cervical Cancer: An Institutional Experience. Manders Dustin B,Sims Travis T,Bailey April,Hwang Lindsay,Richardson Debra L,Miller David S,Kehoe Siobhan M,Albuquerque Kevin V,Lea Jayanthi S American journal of clinical oncology OBJECTIVE:Cervical cancer metastatic to the para-aortic lymph nodes (PALNs) carries a poor prognosis. Despite extended-field radiation therapy (EFRT), only 30% to 50% of patients will survive 3 years. We sought to examine the treatment regimens used, associated toxicities, and treatment outcomes in patients with cervical cancer metastatic to PALN. METHODS:A retrospective review was performed of all patients with cervical cancer treated at a single institution between January 1, 2007 and November 1, 2014. Included patients had PALN metastases as the most distant site of disease, and all treatment plans were designated as curative. Excluded patients had other distant disease or treatment plans considered palliative. Standard treatment consisted of EFRT with concurrent platinum-based chemotherapy. RESULTS:Fifty-one of 344 patients (14.8%) fulfilled the inclusion criteria. The median age was 48.4 years. Forty-four patients received standard EFRT; 7 also received adjuvant platinum/taxane chemotherapy. Thirty-nine of 51 (76%) of patients achieved a complete response to primary treatment. Twelve of 51 (24%) had persistent disease or progression at the completion of treatment. Of responders, 15 of 39 (38%) recurred for an overall treatment failure rate of 27 of 51 (53%). Nineteen of 27 (70%) of treatment failures occurred outside the radiated field. Adjuvant chemotherapy following EFRT was not predictive of progression-free survival or overall survival. PALN diameter ≥1 cm was a significant negative prognostic indicator for overall survival. CONCLUSIONS:Over half of patients with cervical cancer metastatic to the PALN failed extended-field chemoradiation. Most failures occurred outside the radiated field suggesting PALN involvement is a surrogate marker of systemic disease. These findings underscore the need for effective systemic therapy, especially in patients with PALN ≥1 cm in size. 10.1097/COC.0000000000000458
    Predictive factors of para-aortic lymph nodes metastasis in cervical cancer patients: a retrospective analysis based on 723 para-aortic lymphadenectomy cases. Han Xiaotian,Wen Hao,Ju Xingzhu,Chen Xiaojun,Ke Guihao,Zhou Yuqi,Li Jin,Xia Lingfang,Tang Jia,Liang Shanhui,Wu Xiaohua Oncotarget Para-aortic lymph node (PALN) dissection is optional and controversial in patients with stage IB1-IIA2 cervical cancer. This retrospective study investigated PALN involvement patterns and evaluated preoperative clinical factors. A total of 723 consecutive FIGO stage IB1-IIA2 cervical cancer patients were included in the study. All patients underwent radical hysterectomy/radical trachelectomy, pelvic lymph node dissection, and PALN dissection. PALN metastasis was found in 101 (14.0%) patients, and the positive PALN rates of stage IB1, IB2, IIA1, and IIA2 were 8.4%, 11.1%, 17.2% and 21.7%, respectively. A multivariate model suggested age > 46 years (OR: 1.67, 95% confidence interval (CI): 1.08-2.58), tumor size > 3.5 cm (OR: 1.79, 95% CI: 1.12-2.87), and FIGO stage IIA (. IB) (OR: 1.97, 95% CI: 1.25-3.11) all positively correlated with PALN metastasis. When squamous cervical cancer cases were categorically analyzed, a multivariate model indicated age > 46 years (OR: 1.67, 95% CI: 1.00-2.80), FIGO stage IIA (. IB) (OR: 1.76, 95% CI: 1.02-3.02), and squamous cell carcinoma antigen (SCCA) > 6.5 ng/ml (OR: 5.20, 95% CI: 3.07-8.81) all positively correlated with PALN metastasis. Age, tumor size, and FIGO stage correlated with PALN metastasis in cervical cancer, while age, FIGO stage, and SCCA level were predictive in squamous cell carcinoma. 10.18632/oncotarget.16025
    Prediction model for para-aortic lymph node metastasis in patients with locally advanced cervical cancer. Shim Seung-Hyuk,Kim Dae-Yeon,Lee Sun Joo,Kim Soo-Nyung,Kang Soon-Beom,Lee Shin-Wha,Park Jeong-Yeol,Suh Dae-Shik,Kim Jong-Hyeok,Kim Yong-Man,Kim Young-Tak,Nam Joo-Hyun Gynecologic oncology OBJECTIVE:Concurrent chemoradiotherapy is usually administered to patients with locally advanced cervical cancer (LACC). Extended-field chemoradiotherapy is required if para-aortic lymph node (PALN) metastasis is detected. This study aimed to construct a prediction model for PALN metastasis in patients with LACC before definitive treatment. METHODS:Between 2009 and 2016, all consecutive patients with LACC who underwent para-aortic lymphadenectomy at two tertiary centers were retrospectively analyzed. A multivariate logistic model was constructed, from which a prediction model for PALN metastasis was developed and internally validated. Before analysis, risk grouping was predefined based on the likelihood ratio. RESULTS:In total, 245 patients satisfied the eligibility criteria. Thirty-four patients (13.9%) had pathologically proven PALN metastases. Additionally, 16/222 (7.2%) patients with negative PALNs on positron emission tomography/computed tomography (PET/CT) had PALN metastasis. Moreover, 11/105 (10.5%) patients with both negative PALNs and positive pelvic lymph nodes on PET/CT had PALN metastasis. Tumor size on magnetic resonance imaging and PALN status on PET/CT were independent predictors of PALN metastasis. The model incorporating these two predictors displayed good discrimination and calibration (bootstrap-corrected concordance index=0.886; 95% confidence interval=0.825-0.947). The model categorized 169 (69%), 52 (22%), and 23 (9%) patients into low-, intermediate-, and high-risk groups, respectively. The predicted probabilities of PALN metastasis for these groups were 2.9, 20.8, and 76.2%, respectively. CONCLUSION:We constructed a robust model predicting PALN metastasis in patients with LACC that may improve clinical trial design and help clinicians determine whether nodal-staging surgery should be performed. 10.1016/j.ygyno.2016.11.011
    Laparoscopic paraaortic surgical staging in locally advanced cervical cancer: a single-center experience. Vázquez-Vicente D,Fernández Del Bas B,García Villayzán J,Di Fiore H A,Luna Tirado J,Casado Echarren V,García-Foncillas J,Plaza Arranz J,Chiva L Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico BACKGROUND:One aim of this study was to assess the efficacy and safety of laparoscopic paraaortic lymphadenectomy for paraaortic lymph node staging in locally advanced cervical carcinoma. The second aim was to identify prognostic factors in the evolution of this disease and to evaluate how the results of the surgery modify the oncological treatment of patients. MATERIALS AND METHODS:We analyzed 59 patients diagnosed with locally advanced cervical cancer International Federation of Gynecology and Obstetrics stage IB2-IVA who underwent laparoscopic paraaortic lymphadenectomy at our hospital between 2009 and 2015. Depending on the results of the paraaortic lymphadenectomy, treatment consisted of pelvic- or extended-field chemoradiotherapy. RESULTS:The mean age at diagnosis was 52.3 years. The median operative time was 180 min. The mean hospital stay was 1.7 days. The mean number of paraaortic lymph nodes excised was 16.4. Eight patients (13.5%) had positive paraaortic lymph nodes. Thirteen patients (22%) underwent surgery via the transperitoneal route, and 46 (78%) underwent surgery via the retroperitoneal route. The sensitivity and specificity of computerized axial tomography (CT) scanning for detecting paraaortic lymph node involvement was 75 and 86%, respectively. The statistically significant prognostic factors that affected survival were surgical paraaortic lymph node involvement, radiological pelvic lymph node involvement, and radiological tumor size as assessed with nuclear magnetic resonance. The rate of serious complications was 1.7%. CONCLUSIONS:Pretherapeutic laparoscopic paraaortic lymphadenectomy for locally advanced cervical carcinoma allows the adaption of radiotherapy fields to avoid false-positive and false-negative imaging results. 10.1007/s12094-018-1878-4
    Extra-peritoneal laparoscopic para-aortic lymphadenectomy for staging of uterine cervix carcinoma. Neveu M-E,Bentivegna E,Gouy S Journal of visceral surgery 10.1016/j.jviscsurg.2017.01.005
    Indications and techniques for robotic pelvic and para-aortic lymphadenectomy in gynecologic oncology. Wisner Ketura Preya A,Gupta Sarika,Ahmad Sarfraz,Holloway Robert W Journal of surgical oncology Robotic-assisted laparoscopy is now the most common surgical method for treatment of early-stage endometrial, cervical, and a growing number of ovarian cancers in the U.S. Para-aortic and pelvic lymphadenectomy is integral to surgical staging and subsequent treatment planning. This article reviews current staging outcomes with robotic surgery for gynecologic cancers, and describes both trans-peritoneal, extra-peritoneal aortic dissection techniques, and the integration of pelvic sentinel lymph node mapping. 10.1002/jso.24005
    Para-aortic nodal metastases in cervical cancer: a blind spot in the International Federation of Gynecology and Obstetrics staging system: current diagnosis and management. Hwang Lindsay,Bailey April,Lea Jayanthi,Albuquerque Kevin Future oncology (London, England) In cervical cancer, para-aortic nodal (PALN) metastases at presentation is a strong indicator of poor prognosis. Despite this, International Federation of Gynecology and Obstetrics staging system does not require evaluation of lymph node involvement and does not incorporate clinically detected PALN into the staging system. In the USA, despite screening, a significant number of women still present at an advanced stage often with nodal metastases. While the presence of PALN metastases often indicates occult systemic disease, it is possible with modern therapies to provide long-term control of disease in a percentage of patients. We review the epidemiology, diagnosis and treatment of PALN metastases in cervical cancer outlining advances in modern imaging and combined modality therapies (surgery, chemotherapy and radiation therapy). 10.2217/fon.14.200
    The EANM clinical and technical guidelines for lymphoscintigraphy and sentinel node localization in gynaecological cancers. Giammarile Francesco,Bozkurt M Fani,Cibula David,Pahisa Jaume,Oyen Wim J,Paredes Pilar,Olmos Renato Valdes,Sicart Sergi Vidal European journal of nuclear medicine and molecular imaging The accurate harvesting of a sentinel node in gynaecological cancer (i.e. vaginal, vulvar, cervical, endometrial or ovarian cancer) includes a sequence of procedures with components from different medical specialities (nuclear medicine, radiology, surgical oncology and pathology). These guidelines are divided into sectione entitled: Purpose, Background information and definitions, Clinical indications and contraindications for SLN detection, Procedures (in the nuclear medicine department, in the surgical suite, and for radiation dosimetry), and Issues requiring further clarification. The guidelines were prepared for nuclear medicine physicians. The intention is to offer assistance in optimizing the diagnostic information that can currently be obtained from sentinel lymph node procedures. If specific recommendations given cannot be based on evidence from original scientific studies, referral is made to "general consensus" and similar expressions. The recommendations are designed to assist in the practice of referral to, and the performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for high-quality evaluation of possible metastatic spread to the lymphatic system in gynaecological cancer. The final result has been discussed by a group of distinguished experts from the EANM Oncology Committee and the European Society of Gynaecological Oncology (ESGO). The document has been endorsed by the SNMMI Board. 10.1007/s00259-014-2732-8
    Minilaparoscopy vs Standard Laparoscopy for Sentinel Node Dissection: A Pilot Study. Uccella Stefano,Buda Alessandro,Morosi Chiara,Di Martino Giampaolo,Delle Marchette Martina,Reato Claudio,Casarin Jvan,Ghezzi Fabio Journal of minimally invasive gynecology OBJECTIVE:To compare 3-mm minilaparoscopy and standard 5-mm laparoscopy for sentinel lymph node (SLN) detection in apparent early-stage endometrial cancer (EC). DESIGN:Retrospective study (Canadian Task Force classification II-2). SETTING:Two academic research centers. PATIENTS:Consecutive women with apparent early-stage EC who underwent surgical staging with SLN detection between November 2015 and April 2016. INTERVENTIONS:The surgical approach was a total laparoscopic extrafascial hysterectomy plus bilateral salpingo-oophorectomy and SLN detection. Systematic lymphadenectomy was performed in selected cases. In all patients, SLN detection was performed with cervical injection of indocyanine green and the use of an optical camera with a near-infrared high-intensity light source for detection of fluorescence imaging. All patients who underwent a minilaparoscopic approach (using one 5-mm scope and three 3-mm ancillary trocars) have been enrolled at the University of Insubria, whereas at the San Gerardo Hospital, standard laparoscopy was performed with one 10-mm scope and three 5-mm ancillary trocars. MEASUREMENTS AD MAIN RESULTS:A total of 38 patients were enrolled, including 15 (39.5%) in the 3-mm group and 23 (60.5%) in the 5-mm group. No between-group differences were found in terms of demographic and tumor characteristics. Bilateral SLNs were detected in 73.3% of the patients in the 3-mm group and in 73.9% in the 5-mm group. Operative time, blood loss, hemoglobin drop, hospital stay, and the incidence and severity of complications were similar in the 2 groups. One patient (4.3%) in the standard 5-mm group had a positive SLN result (a micrometastasis in the left external iliac SLN). No positive SLNs were detected in the 3-mm group. CONCLUSION:Minilaparoscopic SLN biopsy appears to be a promising and feasible technique for EC staging. Further research is warranted to investigate the possible benefits of 3-mm instruments in this specific setting. 10.1016/j.jmig.2017.10.003
    Impact of lower limb lymphedema on quality of life in gynecologic cancer survivors after pelvic lymph node dissection. Kim Se Ik,Lim Myong Cheol,Lee Jeong Seon,Lee Yumi,Park KiByung,Joo Jungnam,Seo Sang-Soo,Kang Sokbom,Chung Seung Hyun,Park Sang-Yoon European journal of obstetrics, gynecology, and reproductive biology OBJECTIVE:To evaluate the impact of lower limb lymphedema (LLL) on quality of life (QOL) in cervical, ovarian, and endometrial cancer survivors after pelvic lymph node dissection. STUDY DESIGN:A cross-sectional case-control study was performed using the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). In total, 25 women with LLL and 28 women without LLL completed both questionnaires. RESULTS:The GCLQ-K total symptom score and scores for swelling-general, swelling-limb, and heaviness were significantly higher in the LLL group than in the control group. In the EORTC QLQ-C30, the LLL group reported more financial difficulties compared to the control group (mean score, 16.0 vs. 6.0; P=0.035). Global health status was poorer in the LLL group with borderline statistical significance (mean score, 62.7 vs. 71.4; P=0.069). Spearman's correlations suggested that global health status in the EORTC QLQ-C30 correlated with the GCLQ-K total symptom score (in the LLL group, R=-0.64, P=0.001; in the control group, R=-0.42, P=0.027). CONCLUSIONS:QOL decreases due to LLL-related symptoms and financial difficulty in women with LLL. Well-designed prospective studies are required to confirm these findings. 10.1016/j.ejogrb.2015.06.011
    Randomized study comparing use of THUNDERBEAT technology vs standard electrosurgery during laparoscopic radical hysterectomy and pelvic lymphadenectomy for gynecologic cancer. Fagotti Anna,Vizzielli Giuseppe,Fanfani Francesco,Gallotta Valerio,Rossitto Cristiano,Costantini Barbara,Gueli-Alletti Salvatore,Avenia Nicola,Iodice Raffaella,Scambia Giovanni Journal of minimally invasive gynecology STUDY OBJECTIVE:To compare operative time with use of THUNDERBEAT (TB) vs standard electrosurgery (SES) during laparoscopic radical hysterectomy and pelvic lymphadenectomy to treat gynecologic tumors. DESIGN:Evidence obtained from a properly designed, randomized, controlled trial (Canadian Task Force classification I). SETTING:Gynecologic Oncology Unit of the Catholic University of the Sacred Heart in Rome, Italy. PATIENTS:Fifty patients with early cervical cancer (FIGO stages IA2, IB1, IIA <2 cm) or locally advanced cervical cancer (FIGO stages IB2, IIA >2cm, IIB) who received neoadjuvant treatment (chemotherapy or radiochemotherapy) and demonstrated a complete or partial clinical response and early stage endometrioid endometrial cancer (FIGO stages IB, II) were randomly assigned to undergo TB (arm A) or SES (arm B). INTERVENTION:Laparoscopic radical hysterectomy with bilateral pelvic lymphadenectomy, using an easily reproducible technique was performed. MEASUREMENTS AND MAIN RESULTS:Fifty patients were available for analysis, with 25 women randomly assigned to TB (arm A) and 25 to SES (arm B). The median operative time was 85 minutes for TB vs 115 minutes for SES (p = .001). At multivariate analysis, endometrial cancer (p = .001) and TB (p = .001) were independently associated with shorter operating time. No differences in perioperative outcomes and postoperative complications were observed between the 2 arms. Patients who underwent TB reported less postoperative pain, both at rest (p = .005) and after the Valsalva maneuver (p = .008), with less additional analgesic therapy other than standard therapy required in patients who underwent SES (p = .02). CONCLUSION:TB is associated with shorter operative time and less postoperative pain than is the standard technique (SES) in patients with uterine cancer. 10.1016/j.jmig.2013.12.001
    Should Systematic Infrarenal Para-aortic Dissection Be the Rule in the Pretherapeutic Staging of Primary or Recurrent Locally Advanced Cervix Cancer Patients With a Negative Preoperative Para-aortic PET Imaging? Leblanc Eric,Katdare Ninad,Narducci Fabrice,Bresson Lucie,Gouy Sebastien,Morice Philippe,Ferron Gwenael,Querleu Denis,Martinez Alejandra International journal of gynecological cancer : official journal of the International Gynecological Cancer Society BACKGROUND:Extended-field chemoradiation is the usual management of patients with locally advanced cervical cancer (LACC) and para-aortic node metastases (PA pN1). It is efficient but not without morbidity. Assessment of PA lymph node positivity by PA lymphadenectomy is the most accurate method to select the candidates for this treatment. Hence, to clarify the dissection pattern, we wanted to test the true incidence of isolated/skip node metastasis, above the level of the inferior mesenteric artery (IMA). MATERIALS AND METHODS:All patients with LACC and negative magnetic resonance imaging and positron emission tomography-computed tomography imaging at the PA level were offered a laparoscopic staging encompassing a diagnostic laparoscopy followed, if negative, by an extraperitoneal PA lymphadenectomy. All nodes were removed from both common iliac bifurcations up to the left renal vein. Node groups, below and above the IMA, were separately sent to the pathologist for definitive examination. RESULTS:From January 2010 to December 2013, 196 stage IB1 with pelvic pN1, IB2, to IVA LACC patients from 2 cancer centers who fulfilled the criteria were included in this institutional review board-approved study after informed consent. Thirty patients (15%) had PA pN1. Only 1 patient had positive nodes exclusively located above the IMA (3.3% of the pN1 group; 95% confidence interval, 0%-9.7%). Complications were observed in 15 (7.6%) of 196 patients. CONCLUSIONS:Given the very low rate of skip metastases above the IMA and the potential additional morbidity of a systematic extended dissection, a bilateral ilioinframesenteric dissection seems to be an acceptable pattern of PA lymphadenectomy in LACC patients. 10.1097/IGC.0000000000000588
    Lymphadenectomy in locally advanced cervical cancer study (LiLACS): Phase III clinical trial comparing surgical with radiologic staging in patients with stages IB2-IVA cervical cancer. Frumovitz Michael,Querleu Denis,Gil-Moreno Antonio,Morice Philippe,Jhingran Anuja,Munsell Mark F,Macapinlac Homer A,Leblanc Eric,Martinez Alejandra,Ramirez Pedro T Journal of minimally invasive gynecology Radiation treatment planning for women with locally advanced cervical cancer (stages IB2-IVA) is often based on positron emission tomography (PET). PET, however, has poor sensitivity in detecting metastases in aortocaval nodes. We have initiated a study with the objective of determining whether pre-therapeutic laparoscopic surgical staging followed by tailored chemoradiation improves survival as compared with PET/computed tomography (CT) radiologic staging alone followed by chemoradiation. This international, multicenter phase III trial will enroll 600 women with stages IB2-IVA cervical cancer and PET/CT findings showing fluorodeoxyglucose-avid pelvic nodes and fluorodeoxyglucose-negative para-aortic nodes. Eligible patients will be randomized to undergo either pelvic radiotherapy with chemotherapy (standard-of-care arm) or surgical staging via a minimally invasive extraperitoneal approach followed by tailored radiotherapy with chemotherapy (experimental arm). The primary end point is overall survival. Secondary end points are disease-free survival, short- and long-term morbidity with pre-therapeutic surgical staging, and determination of anatomic locations of metastatic para-aortic nodes in relationship to the inferior mesenteric artery. We believe this study will show that tailored chemoradiation after pre-therapeutic surgical staging improves survival as compared with chemoradiation based on PET/CT in women with stages IB2-IVA cervical cancer. 10.1016/j.jmig.2013.07.007
    Clinical Aspects and Prognostic Factors for Survival in Patients with Recurrent Cervical Cancer after Radical Hysterectomy. Hanprasertpong Jitti,Jiamset Ingporn,Geater Alan,Rattanaburi Athithan,Thannil Sarayut Oncology research and treatment BACKGROUND:The aim of this study was to investigate the clinical aspects and prognostic factors for survival in patients with recurrent cervical cancer after radical hysterectomy with node dissection (RHND) for stages IA2-IB1. PATIENTS AND METHODS:Clinicopathologic characteristics of the primary tumor, pattern of recurrence, method of detection, salvage treatment, and outcome were reviewed from the medical records of patients who underwent RHND between 1987 and 2015. Prognostic factors were identified using a Cox regression model. RESULTS:Of 702 patients enrolled in the study, 84 (11.9%) had recurrence. 58, 17, and 9 patients had locoregional, distant, and combined recurrence, respectively. No association between clinicopathologic features and recurrence patterns was observed. Most recurrence patients (63.1%) complained of symptoms prior to examination. The majority of asymptomatic recurrence patients (71.4%) were diagnosed by physical and/or pelvic examination. 5-year overall survival after recurrence (SAR) was 34.3%. On multivariate analysis, pattern of recurrence (p = 0.003), symptom status (p = 0.011), age (p = 0.035), and white blood cell (WBC) count (p = 0.017) were independent prognostic factors for overall SAR. CONCLUSION:Only pattern of recurrence, symptom status, age, and WBC count were found to be prognostic factors in recurrent cervical cancer after RHND. Follow-up programs after RHND should be directed toward early detection of recurrence. 10.1159/000452119
    Laparoscopic Radical Hysterectomy After Concomitant Chemoradiation in Locally Advanced Cervical Cancer: A Prospective Phase II Study. Gallotta Valerio,Ferrandina Gabriella,Chiantera Vito,Fagotti Anna,Fanfani Francesco,Ercoli Alfredo,Legge Francesco,Costantini Barbara,Gueli Alletti Salvatore,Bottoni Carolina,Anchora Luigi Pedone,Nero Camilla,Scambia Giovanni Journal of minimally invasive gynecology OBJECTIVE:To assess the feasibility of laparoscopic radical surgery in patients with locally advanced cervical cancer (LACC) who receive chemoradiation therapy (CT/RT). DESIGN:Prospective phase II study (Canadian Task Force classification II-1). INTERVENTION:Patients with LACC (FIGO stage IB2-III) were evaluated for accrual at the Gynecologic Oncology Unit of Catholic University, Rome/Campobasso. Neoadjuvant CT/RT included whole-pelvic irradiation (total dose, 45.0-50.4 Gy) combined with cisplatin and 5-fluorouracil. Objective response to treatment was evaluated according to Response Evaluation Criteria in Solid Tumors criteria. Laparoscopic radical hysterectomy (RH) plus pelvic and/or aortic lymphadenectomy was attempted within 6 to 8 weeks after CT/RT. The feasibility of laparoscopic RH, as well as the rate, pattern, and severity of early and late postoperative complications, were analyzed. RESULTS:Between January 2010 and October 2013, a total of 58 patients were enrolled into the study. After CT/RT, 23 patients (39.6%) underwent type B2 RH, 31 (53.4%) underwent type C1 RH, and 4 (6.9%) underwent type C2 RH. Pelvic lymphadenectomy was performed in all cases. Laparoscopic RH was feasible in 55 of 58 cases (feasibility rate, 94.8%). No intraoperative complications were recorded. During the observation period (median, 22 months; range, 5-50 months), there were 28 complications, of which only 21.4% were grade 2 complications and 14.3% were grade 3 complications. As of January 2015, disease recurrence was documented in 4 cases (6.9%). CONCLUSION:Total laparoscopic radical surgery is feasible in patients with LACC receiving preoperative CT/RT, providing perioperative outcomes comparable to those registered in early-stage disease. 10.1016/j.jmig.2015.04.014
    Completion surgery after concomitant chemoradiation in locally advanced cervical cancer: a comprehensive analysis of pattern of postoperative complications. Ferrandina Gabriella,Ercoli Alfredo,Fagotti Anna,Fanfani Francesco,Gallotta Valerio,Margariti Alessandro P,Salerno Maria Giovanna,Chiantera Vito,Legge Francesco,Macchia Gabriella,Morganti Alessio G,Valentini Vincenzo,Scambia Giovanni Annals of surgical oncology BACKGROUND:We provided a comprehensive analysis of rate, pattern, and severity of early and late postoperative complications in a very large, single-institution series of locally advanced cervical cancer (LACC) patients administered CT/RT plus radical surgery (RS). METHODS:A total of 362 consecutive LACC (FIGO stage IB2-IVA) patients were submitted to RS after CT/RT at the Gynecologic Oncology Unit of the Catholic University (Rome/Campobasso). At 4 weeks after CT/RT, patients were evaluated for objective response and triaged to radical hysterectomy and pelvic ± aortic lymphadenectomy. Surgical morbidity was classified according to the Chassagne's grading system. RESULTS:Most cases underwent type III-IV radical hysterectomy (N = 313, 86.5 %); pelvic lymphadenectomy was performed in all patients, while 116 patients (32.1 %) were also submitted to aortic lymphadenectomy. A total of 93 patients (25.7 %) experienced any grade postoperative complications, and 60 (16.6 %) had ≥grade 2 complications; grade 3-4 complications occurred in 21 patients (5.8 %). Of all early postoperative complications (N = 100), 31 (31.0 %) were urinary, 9 (9.0 %) were gastrointestinal, and 45 (45.0 %) were vascular. Of all late complications (N = 31), 20 (64.5 %) were urinary, 7 (22.6 %) gastrointestinal, and 2 (6.4 %) were vascular. Multivariate analysis showed that not complete clinical response to treatment retained an independent, unfavorable association with risk of development of postoperative morbidity, while advanced stage, and aortic lymphadenectomy showed only a borderline value. CONCLUSIONS:Failure to achieve clinical complete response to treatment and, to a lesser extent, more advanced stage, and aortic lymphadenectomy, were associated with a higher risk of developing any grade as well as ≥grade 2 complications. 10.1245/s10434-013-3471-y
    Chemoradiation with concomitant boosts followed by radical surgery in locally advanced cervical cancer: long-term results of the ROMA-2 prospective phase 2 study. Ferrandina Gabriella,Gambacorta Antonietta,Gallotta Valerio,Smaniotto Daniela,Fagotti Anna,Tagliaferri Luca,Foti Elvira,Fanfani Francesco,Autorino Rosa,Scambia Giovanni,Valentini Vincenzo International journal of radiation oncology, biology, physics PURPOSE:This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer. METHODS AND MATERIALS:Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatin (20 mg/m(2), days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m(2)/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; β error = 0.1). RESULTS:pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2. CONCLUSIONS:Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very encouraging local control rate, with acceptable toxicity. 10.1016/j.ijrobp.2014.07.033
    Neoadjuvant chemotherapy followed by robotic radical hysterectomy in locally advanced cervical cancer: a multi-institution study. Vizza Enrico,Corrado Giacomo,Zanagnolo Vanna,Tomaselli Tiziana,Cutillo Giuseppe,Mancini Emanuela,Maggioni Angelo Gynecologic oncology OBJECTIVE:Minimally invasive surgery has been performed in locally advanced cervical cancer (LACC) without adverse effect in patient's overall prognosis and survival. The aim of this report is to evaluate the feasibility and morbidity of total robotic radical hysterectomy (TRRH) with pelvic lymphadenectomy in patients with LACC after neo-adjuvant chemotherapy (NACT). METHODS:From February 2008 to April 2013 a retrospective data collection of women undergoing TRRH for cervical cancer stage FIGO IB2 to IIB, after neo-adjuvant chemotherapy, was conducted at "Regina Elena" National Cancer Institute of Rome and European Institute of Oncology of Milan. All patients deemed operable underwent TRRH with pelvic lymphadenectomy within 4 weeks from the last chemotherapy cycle. RESULTS:Median operative time was 225 min (range, 105-387 min). The median blood loss was 150 mL (range, 30-700 mL). The median number of removed pelvic lymph nodes was 23 (range, 8-69). Sixteen patients had an optimal response (12 PCR, 4 pPR1) to chemotherapy, 33 patients had a pPR2 and 11 patient showed stable disease. Adjuvant therapy was administrated in 36 patients (60%). We experienced one intra-operative complication and 19 post-operative complications, but no conversions to laparotomy were necessary to manage these complications. Six patients received a blood transfusion. At the time of this report, with a median follow-up of 28.9 months, 50 patients (83%) are free from recurrence. CONCLUSION:This experience demonstrates the feasibility of TRRH pelvic lymphadenectomy after NACT in LACC with good accuracy and safety. 10.1016/j.ygyno.2014.02.035
    Can a sentinel node mapping algorithm detect all positive lymph nodes in cervical cancer? de Freitas Rosyane Rena,Baiocchi Glauco,Hatschbach Sérgio Bruno Bonatto,Linhares José Clemente,Guerreiro João Antônio,Minari Claudiane Ligia,Ribeiro Reitan,Jung Juliana,Zukovski Taiza,Lopes Ademar Annals of surgical oncology OBJECTIVES:The aims of this study were to determine the sensitivity and negative predictive value (NPV) of sentinel lymph node (SLN) detection in cervical cancer using a combination technique, and to test the SLN algorithm that was proposed by the Memorial Sloan Kettering Cancer Center (MSKCC). METHODS:The study included 57 FIGO stage IA2-IIA patients who were treated at the Erasto Gaertner Hospital, Curitiba, from 2008 to 2010. The patients underwent SLN mapping by technetium lymphoscintigraphy and patent blue dye injection. Following SLN detection, standard radical hysterectomy, including parametrectomy and systematic bilateral pelvic lymphadenectomy, was performed. The SLNs were examined by immunohistochemistry (IHC) when the hematoxylin and eosin results were negative. RESULTS:The median age of patients was 42 years (range 24-71), the median SLN count was 2 (range 1-4), and the median total lymph node (LN) count was 19 (range 11-28). At least one SLN was detected in 48 (84.2 %) patients, while bilateral pelvic detection of SLNs was noted in 28 (58.3 %) cases-one case had bilateral pelvic SLNs and a para-aortic SLN, 19 (39.6 %) had unilateral pelvic LNs, and one (2.1 %) had an SLN in the para-aortic area. Metastatic LNs were found in 9 of 57 (15.8 %) patients. Eight of nine patients with LN metastasis had a positive SLN, yielding an overall sensitivity of 88.9 % and NPV of 97.5 %. Of the 75 sides that were mapped, the SLN detection method predicted LN involvement in 74 (98.6 %) hemi-pelvises. A total of ten hemi-pelvises had LN metastasis, nine of which involved the SLN, resulting in a sensitivity of 90 %, NPV of 98.5 %, and a false negative (FN) of 10 %. In two cases (4.2 %), the SLN was positive only after IHC. CONCLUSIONS:Our SLN procedure is a safe and accurate technique that increases metastatic nodal detection rates by 4.2 % after IHC. The SLN method performed better when analyzing each side; however, one FN occurred, even after applying the MSKCC algorithm. 10.1245/s10434-014-4245-x
    Value and advantages of preoperative sentinel lymph node imaging with SPECT/CT in cervical cancer. Klapdor Ruediger,Mücke Johanna,Schneider Michael,Länger Florian,Gratz Klaus-Friedrich,Hillemanns Peter,Hertel Hermann International journal of gynecological cancer : official journal of the International Gynecological Cancer Society OBJECTIVE:Precise detection of sentinel lymph nodes (SLNs) seems to be a crucial factor for optimized treatment of cervical cancer. We assess the use of single photon emission computed tomography combined with computed tomography (SPECT/CT) as an alternative to lymphoscintigraphy (LSG) for preoperative identification of SLN. METHODS:This study was performed in a prospective, unicentric setting. Patients with cervical carcinoma were scheduled for surgery and additional SLN labeling by peritumoral injection of 10 MBq technetium-99m-nanocolloid and patent blue. Thirty minutes after injection, LSG and SPECT/CT were carried out. We evaluated the number of SLNs detected intraoperatively in LSG and SPECT/CT and the histologic findings of SLN and non-SLN. Subsequently, we determined the impact of these results on the therapeutic approach. RESULTS:This represents the largest study about SPECT/CT for SLN detection in cervical cancer so far. Between August 2008 and March 2013, 59 cervical cancer patients underwent intraoperative SLN detection. In addition, 51 of these patients underwent preoperative LSG and SPECT/CT. Imaging with SPECT/CT detected singular SLN at significantly higher rate (47/51, 92.2%) than that with planar LSG (43/51, 84.3%, P = 0.044). Furthermore, SPECT/CT performed better than LSG regarding the total number of detected SLN (SPECT/CT median, 3 [0-18]; LSG median, 2 [0-15]) and detection rates per pelvic side (SPECT/CT 76.9%, LSG 69.2%, P < 0.01). Whenever SLN detection succeeded, histologic evaluation of SLN correctly predicted the lymph node status per patient's side. Using this type of diagnostic approach for lymph node staging, we reached sensitivity of 100% and negative predictive value of 100% at a rate of false-negative results of 0% even in tumors larger than 4 cm. CONCLUSIONS:Single photon emission computed tomography combined with computed tomography imaging leads to improved rates of SLN detection and better anatomic correlation compared with planar LSG. Thus, intraoperative detection of SLN can be improved by preoperative SPECT/CT imaging. This enhances the clinical value of SLN technique and improves the oncologic safety of SLN concept. 10.1097/IGC.0000000000000032
    Extended field radiotherapy with or without chemotherapy in patients with cervical cancer and positive para-aortic lymph nodes: a single institution retrospective review. Ng Boon Huat,Rozita Am,Adlinda A,Lee Wei Ching,Wan Zamaniah Wi Asian Pacific journal of cancer prevention : APJCP BACKGROUND:Positive para-aortic lymph node (PALN) at diagnosis in cervical cancer patients confers an unfavorable prognosis. This study reviewed the outcomes of extended field radiotherapy (EFRT) and concurrent chemotherapy with extended field RT (CCEFRT) in patients with positive PALN at diagnosis. MATERIALS AND METHODS:Medical records of 407 cervical cancer patients between 1st January 2002 to 31st December 2012 were reviewed. Some 32 cases with positive PALN were identified to have received definitive extended field radiotherapy with or without chemotherapy. Treatment outcomes, clinicopathological factors affecting survival and radiotherapy related acute and late effects were analyzed. RESULTS:Totals of 13 and 19 patients underwent EFRT and CCEFRT respectively during the period of review. The median follow-up was 70 months. The 5-year overall survival (OS) was 40% for patients who underwent CCEFRT as compared to 18% for patients who had EFRT alone, with median survival sof 29 months and 13 months, respectively. The 5-years progression free survival (PFS) for patients who underwent CCEFRT was 32% and 18% for those who had EFRT. Median PFS were 18 months and 12 months, respectively. Overall treatment time (OTT) less than 8 weeks reduced risk of death by 81% (HR=0.19). Acute side effects were documented in 69.7% and 89.5% of patients who underwent EFRT and CCEFRT, respectively. Four patients (12.5%) developed radiotherapy late toxicity and there was no treatment-related death observed. CONCLUSIONS:CCEFRT is associated with higher 5-years OS and median OS compared to EFRT and with tolerable level of acute and late toxicities in selected patients with cervical cancer and PALN metastasis. 10.7314/apjcp.2015.16.9.3827
    Perioperative morbidity and rate of upstaging after laparoscopic staging for patients with locally advanced cervical cancer: results of a prospective randomized trial. Köhler Christhardt,Mustea Alexander,Marnitz Simone,Schneider Achim,Chiantera Vito,Ulrich Uwe,Scharf Jens-Peter,Martus Peter,Vieira Marcelo Andrade,Tsunoda Audrey American journal of obstetrics and gynecology OBJECTIVE:The International Federation of Gynecology and Obstetrics (FIGO) staging for cervical cancer is based on clinical examination. Previous studies have demonstrated significant upstaging with surgical staging. However, no randomized trial has ever shown a survival benefit when radiation combined with chemoradiation (RCTX) is modified according to surgical staging. The objective of the study was to evaluate the feasibility and outcomes of surgical staging prior to radical RCTX treatment among patients with locally advanced cervical cancer in the setting of a larger, prospective, randomized study (the Uterus-11 study of the German Gynecologic Oncology Group). STUDY DESIGN:Between 2009 and 2013, 255 patients with advanced cervical cancer (FIGO IIB-IVA) were randomized to surgical staging and RCTX (arm A) or RCTX (arm B). RCTX in both arms included pelvic external beam radiotherapy with weekly cisplatin at 40 mg/m(2) and brachytherapy. Extended-field radiation was performed in cases of confirmed paraaortic metastases. RESULTS:One hundred thirty patients were randomized to surgical staging; 121 were eligible for this analysis. The mean patient age was 47.2 years, and the mean body mass index was 26.2 kg/m(2); the FIGO stages were IIB, IIIA, IIIB, and IVA in 85 (70.2%), 4 (3.3%), 29 (24%), and 3 (2.5%) patients, respectively. Arm A and arm B were similar with respect to Karnofsky performance status, histology, comorbidities, and lymphovascular space involvement. The surgical approach was transperitoneal laparoscopy in nearly all patients (93.4%), with no operative mortality. One patient (0.8%) had a conversion to laparotomy; 2 patients had more than 500 mL blood loss; the early postoperative complication rate was 7.3%. A mean of 19 pelvic and 17 paraaortic nodes were removed, with means of 2.4 and 1.3 positive nodes, respectively. RCTX began between 7 and 21 days after surgery. Operative staging led to upstaging in 40 of 121 (33%). CONCLUSION:Surgical staging in patients with locally advanced cervical cancer is safe and does not delay primary RCTX in a randomized study. 10.1016/j.ajog.2015.05.026
    Integrated PET/MRI for whole-body staging of patients with primary cervical cancer: preliminary results. Grueneisen Johannes,Schaarschmidt Benedikt Michael,Heubner Martin,Aktas Bahriye,Kinner Sonja,Forsting Michael,Lauenstein Thomas,Ruhlmann Verena,Umutlu Lale European journal of nuclear medicine and molecular imaging PURPOSE:To assess the diagnostic value of integrated PET/MRI for whole-body staging of cervical cancer patients, as well as to investigate a potential association between PET/MRI derived functional parameters and prognostic factors of cervical cancer. METHODS:The present study was approved by the local institutional review board. Twenty-seven patients with histopathologically confirmed cervical cancer were prospectively enrolled in our study. All patients underwent a whole-body PET/MRI examination after written informed consent was obtained. Two radiologists separately evaluated the PET/MRI data sets regarding the determination of local tumor extent of primary cervical cancer lesions, as well as detection of nodal and distant metastases. Furthermore, SUV and ADC values of primary tumor lesions were analyzed and correlated with dedicated prognostic factors of cervical cancer. Results based on histopathology and cross-sectional imaging follow-up served as the reference standard. RESULTS:PET/MRI enabled the detection of all 27 primary tumor lesions of the uterine cervix and allowed for the correct determination of the T-stage in 23 (85 %) out of the 27 patients. Furthermore, the calculated sensitivity, specificity and diagnostic accuracy for the detection of nodal positive patients (n = 11) were 91 %, 94 % and 93 %, respectively. PET/MRI correctly identified regional metastatic disease (N1-stage) in 8/10 (80 %) patients and non-regional lymph node metastases in 5/5 (100 %) patients. In addition, quantitative analysis of PET and MRI derived functional parameters (SUV; ADC values) revealed a significant correlation with pathological grade and tumor size (p < 0.05). CONCLUSIONS:The present study demonstrates the high potential of integrated PET/MRI for the assessment of primary tumor and the detection of lymph node metastases in patients with cervical cancer. Providing additional prognostic information, PET/MRI may serve as a valuable diagnostic tool for cervical cancer patients in a pretreatment setting. 10.1007/s00259-015-3131-5
    Does postoperative prophylactic irradiation of para-aortic lymph nodes reduce the risk of recurrence in uterine cervical cancer with positive pelvic lymph nodes? Yoshida Kosuke,Kajiyama Hiroaki,Yoshihara Masato,Ikeda Yoshiki,Yoshikawa Nobuhisa,Nishino Kimihiro,Utsumi Fumi,Niimi Kaoru,Suzuki Shiro,Kikkawa Fumitaka International journal of clinical oncology BACKGROUND:In cervical cancer, para-aortic lymph nodes are common sites of metastasis. The purpose of the study was to evaluate the clinical benefits of prophylactic irradiation as postoperative therapy. METHODS:A retrospective cohort study was conducted during 2001-2015 at a single institution. Patients with a high risk of para-aortic lymph nodes recurrence were eligible for this study, and we identified patients who had pelvic lymph node metastasis and underwent radical surgery and concurrent chemo-radiotherapy. As a result, 33 and 46 patients were included in the treatment (prophylactic irradiation) and non-treatment groups, respectively. Baseline differences between the two groups were adjusted with the inverse probability of treatment weighting using propensity scores composed of the independent variables including age, stage, tumor size, pathological findings, lymph node status, and pathological subtypes. RESULTS:In the 68-month median follow-up period (range 6-178 months), 25 patients experienced recurrence, and 17 patients were dead. After adjustment with the inverse probability of treatment weighting, the recurrence rates tended to decrease in the treatment group, but there was no significant difference between the two groups [treatment vs. non-treatment, 29.4% and 44.3%, respectively; hazard ratio, 0.593 (95% CI 0.320-1.099); P = 0.097]. However, adjusted para-aortic lymph nodes recurrence rates were not significantly different [treatment vs. non-treatment, 7.8% and 11.4%, respectively; odds ratio, 0.660 (95% CI 0.187-2.322); P = 0.558]. Moreover, Kaplan-Meier curves showing post-recurrence survival revealed no significant difference between the two groups (P = 0.141). CONCLUSIONS:Prophylactic para-aortic lymph nodes irradiation did not reduce the risk of recurrence. 10.1007/s10147-018-1376-2
    Near-infrared fluorescence for detection of sentinel lymph nodes in women with cervical and uterine cancers (FILM): a randomised, phase 3, multicentre, non-inferiority trial. Frumovitz Michael,Plante Marie,Lee Paula S,Sandadi Samith,Lilja James F,Escobar Pedro F,Gien Lilian T,Urbauer Diana L,Abu-Rustum Nadeem R The Lancet. Oncology BACKGROUND:Accurate identification of sentinel lymph nodes in patients with cancer improves detection of metastatic disease and decreases surgical morbidity. We sought to establish whether indocyanine green fluorescent dye is non-inferior to isosulfan blue dye in detecting sentinel lymph nodes in women with cervical and uterine cancers. METHODS:In this non-inferiority, within-patient comparison study, patients aged 18 years or older with clinical stage I endometrial or cervical cancer undergoing curative surgery were randomly assigned 1:1 to lymphatic mapping with isosulfan blue dye (visualised by white light) followed by indocyanine green (visualised by near-infrared imaging), or indocyanine green followed by isosulfan blue dye. Permuted block randomisation with stratification by study site was done with a computerised random number generator. All participants were masked to their randomisation assignment until after the procedure; however, investigators were not masked to the procedure used. Laparoscopic surgery with the PINPOINT near-infrared fluorescence imaging system (Stryker, Kalamazoo, MI, USA) was used in all cases. The primary outcome was efficacy of intraoperative indocyanine green with near-infrared fluorescence imaging versus that of isosulfan blue dye in the identification of lymph nodes, defined as the number of lymph nodes identified by indocyanine green and isosulfan blue dye, respectively (and confirmed as lymphoid tissue by histology), divided by the number of lymph nodes identified intraoperatively and excised. The study had a 5% non-inferiority margin needed to show non-inferiority of the frequency of lymph node detection with indocyanine green to that with isosulfan blue dye with 80% power at a 5% two-sided significance level. Analyses were done in both per-protocol and modified intention-to-treat populations. The trial was registered with ClinicalTrials.gov, number NCT02209532, and is completed and closed. FINDINGS:Between Dec 21, 2015, and June 19, 2017, 180 patients were enrolled and randomly assigned to the two groups (90 to each group); 176 patients received the intervention and were evaluable (modified intention-to-treat population). 13 patients with major protocol violations were subsequently excluded from the per-protocol population. 517 sentinel nodes were identified in the per-protocol population (n=163), of which 478 (92%) were confirmed to be lymph nodes on pathological processing: 219 (92%) of 238 nodes that were both blue and green, all seven nodes that were blue only, and 252 (95%) of 265 nodes that were green only (p=0·33). Seven sentinel lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. In total, 471 (97%) of 485 lymph nodes were identified with the green dye and 226 (47%) with the blue dye (difference 50%, 95% CI 39-62; p<0·0001). In the modified intention-to-treat population (n=176), 545 nodes were identified, of which 513 (94%) were confirmed to be lymph nodes on pathological processing: 229 (92%) of 248 nodes that were both blue and green, all nine nodes that were blue only, and 266 (95%) of 279 nodes that were green only (p=0·30). Nine sentinal lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. 495 (96%) of 513 nodes were identified with the green dye and 238 (46%) with the blue dye (50%, 39-61; p<0·0001). INTERPRETATION:Indocyanine green dye with near-infrared fluorescence imaging identified more sentinel nodes than isosulfan blue dye in women with cervical and uterine cancers, with no difference in the pathological confirmation of nodal tissue between the two mapping substances. FUNDING:Novadaq. 10.1016/S1470-2045(18)30448-0
    Comparison Study of Laparoscopic Sentinel Lymph Node Mapping in Endometrial Carcinoma Using Carbon Nanoparticles and Lymphatic Pathway Verification. Zuo Jing,Wu Ling Ying,Cheng Min,Bai Ping,Lei Cheng Zhi,Li Ning,Zhang Gong Yi,Zhao Dan,Li Bin Journal of minimally invasive gynecology STUDY OBJECTIVE:To evaluate the detection rate and accuracy of sentinel lymph node (SLN) mapping using cervical and fundal injections of carbon nanoparticles (CNPs) in laparoscopic surgery of endometrioid endometrial cancer (EC) and to identify uterine lymphatic drainage pathways validated by mapping. DESIGN:A prospective consecutive study (Canadian Task Force classification II-2). SETTING:An academic research center. PATIENTS:Consecutive patients with a pathologic diagnosis of early-stage EC scheduled for primary laparoscopic-assisted staging surgery (laparoscopic hysterectomy, bilateral salpingo-oophorectomy, or comprehensive lymphadenectomy). INTERVENTIONS:Enrolled patients underwent laparoscopic SLN mapping with a 50-mg CNP tracer injection. Fifty patients received fundal subserosal injections at 4 sites (the fundal group), whereas 65 patients received cervical submucosal injections at 2 sites (the cervical group). After SLN mapping, all patients underwent laparoscopic staging surgery. MEASUREMENTS AND MAIN RESULTS:No allergic reactions to CNPs were observed in either group. The overall SLN detection rates were 100% and 92% in the cervical and fundal groups, and the bilateral SLN detection rates were 97% and 68% (p < .001), respectively. A total of 12 metastatic SLNs were accurately detected in 5 patients. The sensitivity of metastatic lymph node detection was 100% in the cervical group, which is higher than that in the fundal group (80%). The false-negative rates were 0% and 20%, respectively, in the cervical and fundal groups. Furthermore, we verified 3 uterine lymphatic pathways using the 2 injection methods. The upper paracervical pathway was the most common drainage pathway in both groups (91.4% in the cervical group vs 80.24% in the fundal group), whereas the infundibulopelvic pathway was observed only in the fundal group (15.11%). CONCLUSION:SLN mapping by CNPs in laparoscopic surgery for EC is a safe and effective alternative, with a higher detection rate and better accuracy with cervical injections than fundal injections. The upper paracervical pathway was the most common lymphatic pathway, whereas the infundibulopelvic pathway was only displayed in fundal injections. 10.1016/j.jmig.2018.11.002
    Short-term recurrence and distant metastasis following robotic-assisted radical hysterectomy with pelvic lymphadenectomy and chemoradiotherapy for a stage IB1 cervical adenocarcinoma: A case report and literature review. Tong Jinfei,Yu Hailan,Li Jianqiong,Zhou Jiena,Ma Xudong,Yang Jianhua Medicine RATIONALE:Postoperative concurrent chemoradiotherapy (CCRT) is considered the standard treatment for patients with early stage cervical cancer with positive pelvic nodes, yet many patients with high-risk factors treated with CCRT still suffered from distant metastasis. PATIENT CONCERNS:A 48-year-old woman presented with abnormal vaginal bleeding for 5 months. Thin prep liquid-based cytology test revealed low-grade squamous intraepithelial lesion and the human papillomavirus test (type 58) was positive. Magnetic resonance imaging showed a mass measuring 17 × 15 mm, located predominantly in the posterior lip of uterine cervix. Colposcopy biopsy reported adenocarcinoma of the cervix. DIAGNOSIS:Cervical adenocarcinoma stage IB1. INTERVENTIONS:A robotic-assisted radical hysterectomy with pelvic lymphadenectomy was performed followed by postoperative CCRT. OUTCOMES:Distant metastasis was occurred shortly after postoperative CCRT and the patient died 9 months from initial diagnosis. LESSONS:In cases of new nodule in bones, lower abdominal distension and bloating occurring shortly after CCRT in early stage cervical adenocarcinoma, clinicians should bear in mind that recurrence should be considered. Development of more effective treatment to improve the survival outcomes of patients with postoperative metastasis is needed. 10.1097/MD.0000000000015387
    Robotic single site radical hysterectomy plus pelvic lymphadenectomy in gynecological cancers. Vizza Enrico,Chiofalo Benito,Cutillo Giuseppe,Mancini Emanuela,Baiocco Ermelinda,Zampa Ashanti,Bufalo Arabella,Corrado Giacomo Journal of gynecologic oncology OBJECTIVE:To evaluate the feasibility and the safety of robotic single-site radical hysterectomy (RSSRH) plus pelvic lymphadenectomy (PL) in endometrial or cervical cancer. METHODS:Patients with endometrial cancer (EC) International Federation of Gynecology and Obstetrics (FIGO) stage II, early cervical cancer (ECC) FIGO stage IB1 or locally advanced cervical cancer (LACC) FIGO stage IB2-IIB with clinical response ≥50% after neo-adjuvant chemotherapy (NACT) were enrolled in a prospective cohort trial. All cases were performed using the da Vinci Si Surgical Single Site System®. RESULTS:Between April 2014 and November 2016, twenty patients were included in our pilot study. Three and 17 patients underwent type B1 or C1 RSSRH plus PL, respectively. The median age of patients was 46 years (range, 36-68 years) and the median body mass index was 23.5 kg/m² (range, 19.1-36.3 kg/m²). The median total operative time was 190 minutes (range, 90-310 minutes). The median blood loss was 75 mL (range, 20-700 mL) and the median number of pelvic lymph nodes removed was 16 (range, 5-27). No laparoscopic/laparotomic conversions were reported and the median time to discharge was 6 days (range, 4-16 days). No intra-operative complications occurred while 4 (20%) post-operative complications were reported: one pelvic abscess, one lymphorrea, one bowel perforation, and one vaginal dehiscence. CONCLUSION:RSSRH plus PL is technically feasible in patients affected by gynecological cancer. 10.3802/jgo.2018.29.e2
    Roles of posttherapy F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy. Liu Feng-Yuan,Su Tzu-Pei,Wang Chun-Chieh,Chao Angel,Chou Hung-Hsueh,Chang Yu-Chen,Yen Tzu-Chen,Lai Chyong-Huey European journal of nuclear medicine and molecular imaging PURPOSE:To assess the clinical roles of [F]fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) performed 2-3 months after completion of concurrent chemoradiotherapy (CCRT), along with pretherapy characteristics, in patients with advanced squamous cell carcinoma of the uterine cervix enrolled in a prospective randomized clinical trial. METHODS:Posttherapy PET/CT in patients with advanced FIGO stage or positive pelvic or para-aortic lymph node (PALN) defined on pretherapy PET/CT was classified as positive, equivocal, or negative. Overall survival (OS) rates between patients with different PET/CT results are compared. Pretherapy characteristics are examined for association with posttherapy PET/CT results and for prognostic significance in patients with equivocal or negative PET/CT. RESULTS:PET/CT scans (n = 55) were positive, equivocal and negative in 9, 13 and 33 patients, respectively. All patients with positive scans were confirmed to have residual or metastatic disease and died despite salvage therapies. There is a significant OS difference between patients with positive and equivocal scans (P < .001) but not between patients with equivocal and negative scans (P = .411). Positive pretherapy PALN is associated with positive posttherapy PET/CT (P = .033) and predicts a poorer survival in patients with equivocal or negative posttherapy PET/CT (P < .001). CONCLUSIONS:Positive PET/CT 2-3 months posttherapy implies treatment failure and novel therapy is necessary to improve outcomes for such patients. A more intense posttherapy surveillance may be warranted in patients with positive pretherapy PALN. 10.1007/s00259-018-3957-8
    Independent risk factors for ovarian metastases in stage IA-IIB cervical carcinoma. Zhou Le,Sun Chun-Tang,Lin Lin,Xie Yao,Huang Yan,Li Qiao,Liu Xinghui Acta obstetricia et gynecologica Scandinavica INTRODUCTION:Cervical cancer is a common malignant tumor in women; most cervical cancer patients are premenopausal. Ovarian resection or preservation remains controversial. The purpose of this study was to discover the risk factors for ovarian metastasis in women with stage I-II cervical cancer. MATERIAL AND METHODS:A total of 3292 women with cervical carcinoma who had undergone radical hysterectomy, with pelvic lymphadenectomy and bilateral oophorectomy or wedge resection of ovaries, were included in this multicenter retrospective study. We analyzed patients' demographics, International Federation of Obstetrics and Gynecology stage, and histopathologic records to determine clinicopathologic risk factors of ovarian metastasis. RESULTS:Of the patients, 115 (3.49%) were confirmed to have ovarian metastasis. The ovarian metastasis rate was 2% (56/2794) for squamous cell carcinoma and 11.8% (59/498) for nonsquamous cell carcinoma. The risk factors independently associated with ovarian metastasis were histologic type (odds ratio [OR] 8.76, 95% CI 2.09-19.24), lymph node metastasis (OR 2.57, 95% CI 1.76-4.89), lymphovascular space invasion (OR 2.82, 95% CI 1.98-4.24), and corpus invasion (OR 6.34, 95% CI 2.37-11.42). CONCLUSIONS:The histologic type, lymph node metastasis, lymphovascular space invasion, and corpus invasion were independently associated with ovarian metastasis. Histologic type and corpus invasion were the most important risk factors. Therefore, we suggest that corpus invasion might be a strong contraindication for preservation of the ovaries. 10.1111/aogs.13442
    Total Laparoscopic Resection Surgery for a Cervical Carcinoma that Recurred in the Pelvic Sidewall After Radical Hysterectomy and Adjuvant Concurrent Chemoradiotherapy. Kanao Hiroyuki,Aoki Yoichi,Kato Kazuyoshi,Matoda Maki,Okamoto Sanshiro,Nomura Hidetaka,Omatsu Kohei,Utsugi Kuniko,Takeshima Nobuhiro Journal of minimally invasive gynecology STUDY OBJECTIVE:To show total laparoscopic resection of a cervical carcinoma that recurred at the left pelvic sidewall after radical hysterectomy and concurrent chemoradiotherapy (CCRT). DESIGN:A step-by-step demonstration of the technique in a surgical video, including the strategy for achieving complete surgical resection with negative margins (R0 resection) (Canadian Task Force Classification III). SETTING:For high-risk cervical carcinoma, radical hysterectomy and adjuvant CCRT is the standard treatment, but even this multimodal therapy cannot prevent recurrence. When the recurrent mass is localized in the pelvic cavity, R0 resection offers the most promise; however, for laterally recurring cervical carcinoma, the resectability rate is low, owing mainly to severe adhesion and fibrosis, and thus the morbidity and mortality rates are high. Because laparoscopy optimizes visualization and provides for meticulous dissection, laparoscopic surgery can be advantageous over open surgery for resection of cervical carcinoma recurring at the pelvic sidewall after radical hysterectomy and adjuvant CCRT. INTERVENTIONS:A 48-year-old woman with stage IB2 cervical adenocarcinoma had undergone radical hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and, because lymph node metastasis was found in the removed lymph nodes, adjuvant CCRT. At 6 months after completion of this multimodal therapy, a recurrent mass was detected at the left pelvic sidewall. The mass involved the left ureter, bladder, left internal iliac vessels, and endopelvic fascia, and left renal function was unrecoverable. Tumor excision and left nephroureterectomy were performed laparoscopically. The total operating time was 608 minutes, blood loss volume was 250 mL, and blood transfusion was not required. Complete tumor clearance (R0 resection) was achieved by resection of the left internal iliac vessels, left internal obturator muscle, left pubococcygeal muscle, left ureter, and bladder. There were no postoperative complications. Institutional Review Board approval was obtained through our local Ethics Committee in Cancer Institute hospital. CONCLUSION:Complete laparoscopic resection surgery for recurrent cervical carcinoma at the pelvic sidewall after radical hysterectomy and adjuvant CCRT is technically feasible. The good visualization and meticulous dissection provided during laparoscopic surgery make the approach advantageous for the management of laterally recurrent cervical carcinoma. 10.1016/j.jmig.2017.04.014
    Association of tumor differentiation grade and survival of women with squamous cell carcinoma of the uterine cervix. Matsuo Koji,Mandelbaum Rachel S,Machida Hiroko,Purushotham Sanjay,Grubbs Brendan H,Roman Lynda D,Wright Jason D Journal of gynecologic oncology OBJECTIVE:To examine the association between tumor grade and survival for women with squamous cervical cancer. METHODS:This retrospective observational study utilized the Surveillance, Epidemiology, and End Result program data between 1983 and 2013 to examine women with squamous cervical cancer with known tumor differentiation grade. Multivariable analyses were performed to assess independent associations between tumor differentiation grade and survival. RESULTS:A total of 31,536 women were identified including 15,175 (48.1%) with grade 3 tumors, 14,084 (44.7%) with grade 2 neoplasms and 2,277 (7.2%) with grade 1 tumors. Higher tumor grade was significantly associated with older age, higher stage disease, larger tumor size, and lymph node metastasis (all, p<0.001). In a multivariable analysis, grade 2 tumors (adjusted-hazard ratio [HR]=1.21; p<0.001) and grade 3 tumors (adjusted-HR=1.45; p<0.001) were independently associated with decreased cause-specific survival (CSS) compared to grade 1 tumors. Among the 7,429 women with stage II-III disease who received radiotherapy without surgical treatment, grade 3 tumors were independently associated with decreased CSS compared to grade 2 tumors (adjusted-HR=1.16; p<0.001). Among 4,045 women with node-negative stage I disease and tumor size ≤4 cm who underwent surgical treatment without radiotherapy, grade 2 tumors (adjusted-HR=2.54; p=0.028) and grade 3 tumors (adjusted-HR=4.48; p<0.001) were independently associated with decreased CSS compared to grade 1 tumors. CONCLUSION:Our study suggests that tumor differentiation grade may be a prognostic factor in women with squamous cervical cancer, particularly in early-stage disease. Higher tumor grade was associated with poorer survival. 10.3802/jgo.2018.29.e91
    Robotic Radical Hysterectomy After Concomitant Chemoradiation in Locally Advanced Cervical Cancer: A Prospective Phase II Study. Gallotta Valerio,Chiantera Vito,Conte Carmine,Vizzielli Giuseppe,Fagotti Anna,Nero Camilla,Costantini Barbara,Lucidi Alessandro,Cicero Carla,Scambia Giovanni,Ferrandina Gabriella Journal of minimally invasive gynecology STUDY OBJECTIVE:To assess the feasibility of total robotic radical surgery (TRRS) in patients with locally advanced cervical cancer (LACC) who receive chemoradiation therapy (CT/RT). DESIGN:A prospective (preplanned) study of a nonrandomized controlled trial (Canadian Task Force classification level 2). SETTING:Catholic University of the Sacred Hearth, Rome, Italy. PATIENTS:Between September 2013 and January 2016, a total of 40 patients with LACC (Fédération Internationale de Gynécologie et d'Obstétrique stage IB2-III) were enrolled in the study. INTERVENTIONS:Robotic radical hysterectomy (RRH) plus pelvic and/or aortic lymphadenectomy was attempted within 6 weeks after CT/RT. The feasibility of TRRS as well as the rate, pattern, and severity of early and late postoperative complications were analyzed. MEASUREMENTS AND MAIN RESULTS:After CT/RT, 29 patients (72.5%) underwent type B2 RRH, and 11 (27.5%) underwent type C1 RRH. Pelvic lymphadenectomy was performed in all cases. TRRS was successful in 39 of 40 cases (feasibility rate = 97.5%). In patients successfully completing TRRS, the median operating time was 185 minutes (range, 100-330 minutes), and the median blood loss was 100 mL (range, 50-300 mL). The median time of hospitalization counted from the first postoperative day was 2 days (range, 1-4 days). No intraoperative complications were recorded. During the observation period (median = 18 months; range, 4-28 months), 9 of 40 (22.5%) experienced postoperative complications, for a total number of 12 complications. As of April 2016, recurrence of disease was documented in 5 cases (12.5%). CONCLUSION:TRRS is feasible in LACC patients administered preoperative CT/RT, providing perioperative outcomes comparable with those registered in early-stage disease, and LACC patients receiving neoadjuvant chemotherapy. 10.1016/j.jmig.2016.09.005
    Patterns of lymph node metastasis in locally advanced cervical cancer. Liu Zhikai,Hu Ke,Liu An,Shen Jie,Hou Xiaorong,Lian Xin,Sun Shuai,Yan Junfang,Zhang Fuquan Medicine The aim of this study was to investigate patterns and locations of lymph node metastasis in locally advanced cervical cancers.A total of 244 consecutive patients with stage IIb cervical cancer were retrospectively evaluated. Contrast-enhanced CT scans were used for lymph node grading. Lymph nodes with the shortest axis (>1 cm) were categorized as positive and those between 0.5 and 1 cm were categorized as suspicious. All lymph nodes (LNs) were also classified by their anatomic locations.Nine hundred thirty-one LNs (136 positive and 795 suspicious) were identified. Sixty-three (25.8%) patients had positive LNs, and 153 (62.7%) patients had only suspicious LNs. The metastatic pattern was predictable traveling from level 1 (external iliac, internal iliac, obturator, and mesorectum groups) through level 2 (common iliac and presacral groups) to level 3 (para-aortic groups). In most groups, LNs were located within 1.0 cm of main blood vessels. Our novel findings were: presacral LNs metastases were rare (2/244, 0.82%); the left common iliac group (LCI) had significantly more enlarged nodes than the right common iliac group (P = 0.00); the LCI and left down-para-aortic group were further away from blood vessels than expected (1.2 cm and 1.4 cm, respectively); no additional margin was needed in anterolateral direction for external iliac groups.The lymph node metastatic patterns are relatively predicable. Different expansions from vessels should be used to include LNs for different groups. Presacral nodes metastases are rare, and further study is warranted to see whether this region can be excluded from nodal CTV. 10.1097/MD.0000000000004814
    Magnetic resonance image-guided brachytherapy for cervical cancer : Prognostic factors for survival. Kim Yeon-Joo,Kim Joo-Young,Kim Youngkyong,Lim Young Kyung,Jeong Jonghwi,Jeong Chiyoung,Kim Meyoung,Lim Myong Cheol,Seo Sang-Soo,Park Sang-Yoon Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] OBJECTIVE:The purpose of this work was to identify prognostic factors for survival after magnetic resonance image (MRI)-guided brachytherapy combined with external beam radiotherapy for cervical cancer. MATERIAL AND METHODS:External beam radiotherapy of 45-50.4 Gy was delivered by either three-dimensional conformal radiotherapy or helical tomotherapy. Patients also received high-dose-rate MRI-guided brachytherapy of 5 Gy in 6 fractions. RESULTS:We analyzed 128 patients with International Federation of Gynecology and Obstetrics stage IB-IVB cervical cancer who underwent MRI-guided brachytherapy. Most patients (96 %) received concurrent chemotherapy. Pelvic lymph node metastases and para-aortic lymphadenopathies were found in 62 % and 14 % of patients, respectively. The median follow-up time was 44 months. Complete remission was achieved in 119 of 128 patients (93 %). The 5‑year local recurrence-free, cancer-specific, and overall survival rates were 94, 89, and 85 %, respectively. Negative pelvic lymphadenopathy, gross tumor volume (GTV) dose covering 90 % of the target (GTV D90) of >110 Gy, and treatment duration ≤56 days were associated with better overall survival in univariate analyses. Multivariable analysis showed that GTV D90 of >110 Gy and treatment duration ≤56 days were possibly associated with overall survival with near-significant P-values of 0.062 and 0.073, respectively. CONCLUSIONS:The outcome of MRI-guided brachytherapy combined with external beam radiotherapy in patients with cervical cancer was excellent. GTV D90 of >110 Gy and treatment duration ≤56 days were potentially associated with overall survival. 10.1007/s00066-016-1049-x
    [Comparison of the clinical efficacy of different treatments based on radical surgery in stage Ⅰ b2 and Ⅱa2 cervical cancer: a prospective randomized control study]. Li X,Kong W M,Han C,Yan Z,Zhao H,Zhang W Y,Wang J D Zhonghua fu chan ke za zhi OBJECTIVE:To compare the clinical efficacy of different treatments based on radical surgery in stage Ⅰ b2 and Ⅱ a2 cervical cancer through prospective randomized controlled study. METHODS:A total of 133 patients with stage Ⅰ b2 and Ⅱ a2 cervical cancer treated at Beijing Obstetrics and Gynecology Hospital of Capital Medical University during January 2009 to December 2012 were enrolled and randomly assigned to receive one of the following three treatments: preoperative intracavitary irradiation(PII)group, radical hysterectomy(RH)group, and neoadjuvant chemotherapy(NACT)group. Operation method included uterine extensive resection, pelvic lymph node excision, with or without para-aortic lymph node resection. The recent curative effect and side effect of preoperative treatment were observed. The operation time, intraoperative blood loss, surgical complications, postoperative pathological risk factors and postoperative adjuvant therapy and side effect, the survival situation were evaluated among the 3 groups. RESULTS:(1)The response rates were 88%(37/42)and 82%(37/45)respectively of the PII group and NACT group. The difference was insignificant(P=0.528). Side effects were less in the PII group. Only 5 patients(12% , 5/42)had slight gastrointestinal reaction. Myelosuppression and gastrointestinal reaction in NACT group were 76%(34/45)and 67%(30/45)respectively, which were more serious than that in group PII group(P<0.05).(2)Intraoperative blood loss and operation time in PII group [(678± 239)ml and(181±39)minutes]and NACT group [(625±137)ml and(168±25)minutes]had a decreasing trend compared with that in RH group [(711 ± 319)ml and(202 ± 64)minutes], but the differences were no significant(P >0.05). NACT group could shorten operation time compared with the RH group(P <0.05). The lymph node metastases rate were 30%(14/46), 29%(12/42)and 29%(13/45)and the deep stromal invasion rate were 22%(10/46), 31%(13/42)and 31%(14/45)in RH group, PII group and NACT group respectively(all P>0.05). The lymph-vascular space involvement(LVSI)in NACT group was significantly lower than that in RH group [31%(14/45)vs 57%(26/46), P=0.015]. The number of patients with histological risk factors in NACT group was higher thanthat in RH group [27%(12/45)vs 9%(4/46), P= 0.024]. All surgery were successfully completed and no treatment-related deaths occurred in three groups. The incidence of 3-4 grade adverse reactions evaluated by the common terminology criteria for adverse event(CTCAE)was 13%(6/46), 14%(6/42), 18%(8/45)in RH group, PII group and NACT group respectively(P=0.855). Three-year disease free survival(PFS)were 74.0%, 78.5% and 80.0%, and 3-year overall survival(OS)were 80.4%, 83.3% and 84.4% in RH group, PII group and NACT group respectively(all P>0.05). CONCLUSIONS:The recent curative effect of PII and NACT were similar. They couldn't improve 3-year of PFS and OS of the patients with Ⅰb2 and Ⅱa2 stage cervical cancer. But NACT can reduce the operation difficulty and can reduce the incidence of postoperative pathological risk factors, which could reduce postoperative adjuvant therapy. 10.3760/cma.j.issn.0529-567X.2016.07.008
    SENTICOL III: an international validation study of sentinel node biopsy in early cervical cancer. A GINECO, ENGOT, GCIG and multicenter study. Lecuru Fabrice R,McCormack Mary,Hillemanns Peter,Anota Amelie,Leitao Mario,Mathevet Patrice,Zweemer Ronald,Fujiwara Keiichi,Zanagnolo Vanna,Zahl Eriksson Ane Gerda,Hudson Emma,Ferron Gwenael,Plante Marie International journal of gynecological cancer : official journal of the International Gynecological Cancer Society BACKGROUND:Radical hysterectomy and complete pelvic lymphadenectomies are the most commonly performed procedures for women with early-stage cervical cancer. Sentinel lymph node (SLN) mapping could be an alternative to routine pelvic lymphadenectomy, aiming to diagnose accurately nodal extension and decrease lymphatic morbidity. PRIMARY OBJECTIVE:To compare 3-year disease-free survival and health-related quality of life after SLN biopsy or SLN biopsy + pelvic lymphadenectomy in early cervical cancer. STUDY HYPOTHESIS:We hypothesize that disease-free survival is non-inferior and health-related quality of life superior after SLN biopsy compared with SLN biopsy + pelvic lymphadenectomy. TRIAL DESIGN:International, randomized, multicenter, single-blind trial. The study will be run by teams trained to carry out SLN biopsy, belonging to clinical research cooperative groups or recognized as experts in this field. Patients with an optimal mapping (Memorial Sloan Kettering Cancer Center [MSKCC] criteria) and a negative frozen section will be randomized 1:1 to SLN biopsy only or SLN biopsy + pelvic lymphadenectomy. INCLUSION, EXCLUSION CRITERIA:Patients with early stages (Ia1 with lymphovascular invasion to IIa1) of disease. Histological types are limited to squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma. PRIMARY ENDPOINT:Main endpoint will be co-primary endpoint, associating 3-year disease-free survival and quality of life (QLQ-C30 and QLQ-CX24). SAMPLE SIZE:950 patients need to be randomized.Estimated dates for completing accrual and presenting results: study started on Q2 2018, last accrual is scheduled for Q2 2021, and last follow-up in Q2 2026. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT03386734. 10.1136/ijgc-2019-000332
    Type B Laparoscopic Radical Trachelectomy With Pelvic Lymphadenectomy for Early Cervical Cancer. Martel-Billard Camille,Faller Emilie,Delaine Maia,Boisramé Thomas,Baldauf Jean-Jacques,Akladios Cherif Youssef Journal of minimally invasive gynecology STUDY OBJECTIVE:To demonstrate the technique of laparoscopic radical trachelectomy (LRT) and laparoscopic pelvic lymphadenectomy for early cervical cancer. DESIGN:Case report (Canadian Task Force Classification Study design III). SETTING:Tertiary referral centre in Strasbourg, France. BACKGROUND:Over the past 15 years, gynecologic oncologists have sought ways to preserve female fertility when treating invasive cervical cancer. Many cases of cervical cancer have been diagnosed in young women with a desire to preserve their fertility. As more women are delaying childbearing, fertility preservation has become an important consideration. Radical hysterectomy and bilateral pelvic lymphadenectomy represent the standard surgical treatment for stage IA2-IB1 cervical cancer. In some women with small localized invasive cervical cancer, there is hope for a pregnancy after treatment. Vaginal radical trachelectomy (VRT) is a fertilitypreserving surgical procedure for early-stage cervical cancers. The National Comprehensive Cancer Network has published guidelines stating that radical trachelectomy is part of the standard of care for women desiring to preserve their future fertility. VRTwas introduced in 1987 with its first reported use in 1994, and since then more than 1000 cases of VRT have been reported involving more than 250 live births. The tumor recurrence rate is between 4.2% and 5.3%, and the mortality rate is between 2.5% and 3.2%. However, VRT has several limitations despite results demonstrating the safety of the procedure. One limitation is that it is an inadequate procedure for nulliparous patients and those with history of previous conization with adverse vaginal anatomy. In addition, it is difficult to learn the techniques involved in radical vaginal surgery. PATIENTS:A 26 year-old nulliparous women with a FIGO Stage IB1 squamous cell tumor of the cervix. A first conisation was performed with no safe resection margins. INTERVENTION:In this video we show a type B laparoscopic radical trachelectomy with round ligament and uterine artery preservation. A laparoscopic pelvic lymphadenectomy was also performed. Our institutional review board approved this study. MEASUREMENTS AND MAIN RESULTS:Operative time was 240 minutes. Intraoperative blood loss was less than 100 mL. The operation was performed successfully with no intraoperative complications. Pathological findings demonstrated the presence of a cervical intraepithelial neoplasia 2 on the anterior lips from an 11 o'clock to a 1 o'clock position. Resection margins were safe. The surgical specimen did not show any residual invasive carcinoma. Twenty one lymph nodes were removed, 7 on the right side, and 14 on the left side. No metastatic adenopathy was found. The patient was discharged on day 11. After 5 months, no late complications or recurrence was detected. CONCLUSIONS:LRT appears to be a safe option for women who intend to maintain their desire for a future pregnancy. 10.1016/j.jmig.2016.06.004
    Postoperative chemotherapy for node-positive cervical cancer: Results of a multicenter phase II trial (JGOG1067). Matoda Maki,Takeshima Nobuhiro,Michimae Hirofumi,Iwata Takashi,Yokota Harushige,Torii Yutaka,Yamamoto Yorito,Takehara Kazuhiro,Nishio Shin,Takano Hirokuni,Mizuno Mika,Takahashi Yoshiyuki,Takei Yuji,Hasegawa Tetsuya,Mikami Mikio,Enomoto Takayuki,Aoki Daisuke,Sugiyama Toru Gynecologic oncology OBJECTIVE:This multicenter phase II Japanese Gynecologic Oncology Group study (JGOG1067) was designed to evaluate the efficacy and safety of postoperative chemotherapy in patients with node-positive cervical cancer. METHODS:Patients with stage IB-IIA squamous cervical cancer who underwent radical hysterectomy and were confirmed to have pelvic lymph node metastasis were eligible for this study. The patients postoperatively received irinotecan (CPT-11; 60mg/m intravenously on days 1 and 8) and nedaplatin (NDP; 80mg/m intravenously on day 1). Chemotherapy administration commenced within 6weeks after surgery and was repeated every 28days for up to 5cycles. The primary endpoint of this study was the 2-year recurrence-free survival (RFS) rate. The secondary endpoints were the 5-year overall survival (OS) rate, 5-year RFS rate, and adverse events such as complications of chemotherapy and lower-limb edema. RESULTS:Sixty-two patients were analyzed according to our protocol, among whom 55 (88.7%) completed 5cycles of scheduled treatment. The median follow-up period was 66.1months (range, 16.8-96.6months). The 2-year and 5-year RFS rates were 87.1% (95% confidence interval [CI]: 75.9-99.3) and 77.2% (95% CI: 64.5-85.8), respectively. Fourteen patients (22.5%) experienced recurrence during the follow-up period, 8 of whom died of the disease. The 5-year OS rate in this study was 86.5% (95% CI: 74.8-93.0). Only 9.7% of the patients experienced lymphedema in their legs. CONCLUSION:Postoperative chemotherapy without radiotherapy was found to be very effective in high-risk patients with node-positive cervical cancer. 10.1016/j.ygyno.2018.04.009
    Extended mesometrial resection (EMMR): Surgical approach to the treatment of locally advanced cervical cancer based on the theory of ontogenetic cancer fields. Wolf Benjamin,Ganzer Roman,Stolzenburg Jens-Uwe,Hentschel Bettina,Horn Lars-Christian,Höckel Michael Gynecologic oncology BACKGROUND:Based on ontogenetic-anatomic considerations, we have introduced total mesometrial resection (TMMR) and laterally extended endopelvic resection (LEER) as surgical treatments for patients with cancer of the uterine cervix FIGO stages I B1 - IV A. For a subset of patients with locally advanced disease we have sought to develop an operative strategy characterized by the resection of additional tissue at risk for tumor infiltration as compared to TMMR, but less than in LEER, preserving the urinary bladder function. METHODS:We conducted a prospective single center study to evaluate the feasibility of extended mesometrial resection (EMMR) and therapeutic lymph node dissection as a surgical treatment approach for patients with cervical cancer fixed to the urinary bladder and/or its mesenteries as determined by intraoperative evaluation. None of the patients received postoperative adjuvant radiotherapy. RESULTS:48 consecutive patients were accrued into the trial. Median tumor size was 5cm, and 85% of all patients were found to have lymph node metastases. Complete tumor resection (R0) was achieved in all cases. Recurrence free survival at 5years was 54.1% (95% CI 38.3-69.9). The overall survival rate was 62.6% (95% CI 45.6-79.6) at 5years. Perioperative morbidity represented by grade II and III complications (determined by the Franco-Italian glossary) occurred in 25% and 15% of patients, respectively. CONCLUSION:We demonstrate in this study the feasibility of EMMR as a surgical treatment approach for patients with locally advanced cervical cancer and regional lymph node invasion without the necessity for postoperative adjuvant radiation. 10.1016/j.ygyno.2017.05.007
    Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer. Ramirez Pedro T,Frumovitz Michael,Pareja Rene,Lopez Aldo,Vieira Marcelo,Ribeiro Reitan,Buda Alessandro,Yan Xiaojian,Shuzhong Yao,Chetty Naven,Isla David,Tamura Mariano,Zhu Tao,Robledo Kristy P,Gebski Val,Asher Rebecca,Behan Vanessa,Nicklin James L,Coleman Robert L,Obermair Andreas The New England journal of medicine BACKGROUND:There are limited data from retrospective studies regarding whether survival outcomes after laparoscopic or robot-assisted radical hysterectomy (minimally invasive surgery) are equivalent to those after open abdominal radical hysterectomy (open surgery) among women with early-stage cervical cancer. METHODS:In this trial involving patients with stage IA1 (lymphovascular invasion), IA2, or IB1 cervical cancer and a histologic subtype of squamous-cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, we randomly assigned patients to undergo minimally invasive surgery or open surgery. The primary outcome was the rate of disease-free survival at 4.5 years, with noninferiority claimed if the lower boundary of the two-sided 95% confidence interval of the between-group difference (minimally invasive surgery minus open surgery) was greater than -7.2 percentage points (i.e., closer to zero). RESULTS:A total of 319 patients were assigned to minimally invasive surgery and 312 to open surgery. Of the patients who were assigned to and underwent minimally invasive surgery, 84.4% underwent laparoscopy and 15.6% robot-assisted surgery. Overall, the mean age of the patients was 46.0 years. Most patients (91.9%) had stage IB1 disease. The two groups were similar with respect to histologic subtypes, the rate of lymphovascular invasion, rates of parametrial and lymph-node involvement, tumor size, tumor grade, and the rate of use of adjuvant therapy. The rate of disease-free survival at 4.5 years was 86.0% with minimally invasive surgery and 96.5% with open surgery, a difference of -10.6 percentage points (95% confidence interval [CI], -16.4 to -4.7). Minimally invasive surgery was associated with a lower rate of disease-free survival than open surgery (3-year rate, 91.2% vs. 97.1%; hazard ratio for disease recurrence or death from cervical cancer, 3.74; 95% CI, 1.63 to 8.58), a difference that remained after adjustment for age, body-mass index, stage of disease, lymphovascular invasion, and lymph-node involvement; minimally invasive surgery was also associated with a lower rate of overall survival (3-year rate, 93.8% vs. 99.0%; hazard ratio for death from any cause, 6.00; 95% CI, 1.77 to 20.30). CONCLUSIONS:In this trial, minimally invasive radical hysterectomy was associated with lower rates of disease-free survival and overall survival than open abdominal radical hysterectomy among women with early-stage cervical cancer. (Funded by the University of Texas M.D. Anderson Cancer Center and Medtronic; LACC ClinicalTrials.gov number, NCT00614211 .). 10.1056/NEJMoa1806395
    Incidence of Histologically Proven Pelvic and Para-Aortic Lymph Node Metastases and Rate of Upstaging in Patients with Locally Advanced Cervical Cancer: Results of a Prospective Randomized Trial. Tsunoda Audrey Tieko,Marnitz Simone,Soares Nunes Joao,Mattos de Cunha Andrade Carlos Eduardo,Scapulatempo Neto Christovam,Blohmer Jens-Uwe,Herrmann Jörg,Kerr Ligia Maria,Martus Peter,Schneider Achim,Favero Giovanni,Köhler Christhardt Oncology BACKGROUND:Surgical staging is associated with a significant rate of upstaging compared to clinical/radiological staging in patients with locally advanced cervical cancer. OBJECTIVE:To analyze the stage-specific percentage of pelvic and para-aortic lymph node metastases and the upstaging ratio in a prospective randomized trial (Uterus-11). METHODS:FIGO stage IIB-IVA cervical cancer patients were randomized to surgical staging (arm A) or to clinical staging and primary chemoradiation (arm B). Arm B patients underwent CT-guided biopsy of suspicious para-aortic lymph nodes. Confirmed para-aortic metastasis patients received extended-field radiation therapy. RESULTS:A total of 234 patients were enrolled, including 120 (arm A) and 114 (arm B) treated per protocol. The groups were well balanced. Pelvic and para-aortic lymph node metastases were identified after surgical staging in 51 and 24% of patients, respectively (p < 0.001). Pelvic and para-aortic lymph node metastases were confirmed in 45 and 20% of IIB patients and in 71 and 37% of IIIB patients, respectively. Upstaging occurred in 39/120 (33%) in arm A and in 9/114 (8%) in arm B (p < 0.001). CONCLUSION:The histological results in both groups led to a considerable rate of upstaging. Oncological data from the Uterus-11 study may reveal whether modified therapy translates into a survival benefit. 10.1159/000453666
    Efficacy and safety outcomes of robotic radical hysterectomy in Chinese older women with cervical cancer compared with laparoscopic radical hysterectomy. Luo Cheng,Liu Mei,Li Xiuli BMC women's health BACKGROUND:Recently, as a complex integrating a number of modern high-tech means, robotic surgery system is a well-deserved revolutionary tool in globally minimally invasive surgical field. For the first time in China, the objective of this study was to evaluate the efficacy and safety outcomes of robotic radical hysterectomy (RRH) in Chinese older women with cervical cancer compared with laparoscopic radical hysterectomy (LRH). METHODS:In this prospective, randomized and double-blinded study, 60 Chinese older women with cervical cancer were evenly divided to accept the RRH or LRH. Follow-up period lasted for 24 months. RESULTS:Median age for the entire cohort was 65 (range: 61-69) years. There was no difference in International Federation of Gynecology and Obstetrics (FIGO) stages and cell types between two groups (p > 0.05 for all). Uterine size, tumor size, vaginal length and numbers of left and right pelvic lymph nodes did not differ between two groups (p > 0.05 for all). No difference was observed in numbers of left and right lymph node metastasis (p > 0.05 for all). All patients had negative margins without conversion to laparotomy. There were significantly less postoperative complications in the RRH group than in the LRH group (p < 0.05). Shorter indwelling time of bladder and drain catheters was observed in the RRH group than in the LRH group (p < 0.05 for all). Length of postoperative hospital stay in the RRH group was significantly shorter compared with that in the LRH group (p < 0.05). Patients in two groups similarly experienced the recurrence and death (p > 0.05 for all). CONCLUSIONS:This study demonstrated that RRH provided additional benefits for Chinese older women with cervical cancer because of less complications and faster recovery compared with LRH. Meanwhile, this study supported an equivalence of surgical qualities and survival outcomes of RRH to LRH. Robotics-assisted surgical method is effective, safe and feasible for Chinese older women with cervical cancer. 10.1186/s12905-018-0544-x
    Incidence of Lymph Node Metastases in Women With Low-Risk Early Cervical Cancer (<2 cm) Without Lymph-Vascular Invasion. Minig Lucas,Fagotti Anna,Scambia Giovanni,Salvo Gloria,Patrono María Guadalupe,Haidopoulos Dimitrios,Zapardiel Ignacio,Domingo Santiago,Sotiropoulou Maria,Chisholm Gary,Ramirez Pedro T International journal of gynecological cancer : official journal of the International Gynecological Cancer Society OBJECTIVE:To determine the incidence of lymph node metastasis in women with low-risk cervical cancer stage IA2 or IB1 (<2 cm) without lymph-vascular space invasion. METHODS:A multicenter retrospective study was performed in patients who underwent radical or simple hysterectomy, conization, or trachelectomy plus pelvic lymphadenectomy for cervical cancer between January 2000 and June 2016. RESULTS:A total of 271 patients were included in the study. Median age and body mass index were 46 years (range, 23-77 years) and 24 kg/m (range, 18-48 kg/m), respectively. Twenty-two patients had stage IA2 (8.1%), and 249 (91.9%) had stage IB1. The median tumor size was 14 mm (range, 5-20 mm). Tumor grades were 1 (n = 63 [23.2%]), 2 (n = 120 [44.3%]), 3 (n = 63 [23.2%]), and unknown (25 [9.2%]). Median depth stromal invasion was 6 mm (range, 3-20 mm). Histologic subtypes included squamous (n = 171 [63.1%]), adenocarcinoma (n = 92 [33.9%]), and adenosquamous (n = 8 [3.0%]). Overall incidence of lymph node metastasis was 2.9% (n = 8). The incidence of lymph node involvement in G1, G2, and G3 was 0% (0/63), 5% (6/120), and 3.1% (2/63), respectively. No patient with stage IA2 (regardless of grade or histology) or G1 cervical cancer less than 2 cm (stage IB1) had lymph node metastasis. CONCLUSIONS:Patients with stage IA2 or IB1 (G1) with tumor size of less than 2 cm and no lymph-vascular space invasion may not need lymph node evaluation. On the other hand, 95% and 98% of patients with grade 2 or 3 tumors, respectively, could potentially undergo an unnecessary lymphadenectomy. Further studies with bigger sample size are required to confirm these results. 10.1097/IGC.0000000000001236
    Robot-assisted approach to cervical cancer (RACC): an international multi-center, open-label randomized controlled trial. Falconer Henrik,Palsdottir Kolbrun,Stalberg Karin,Dahm-Kähler Pernilla,Ottander Ulrika,Lundin Evelyn Serreyn,Wijk Lena,Kimmig Rainer,Jensen Pernille Tine,Zahl Eriksson Ane Gerda,Mäenpää Johanna,Persson Jan,Salehi Sahar International journal of gynecological cancer : official journal of the International Gynecological Cancer Society BACKGROUND:Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival. PRIMARY OBJECTIVE:To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy. STUDY HYPOTHESIS:Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes. TRIAL DESIGN:Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden. MAJOR INCLUSION/EXCLUSION CRITERIA:Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years. PRIMARY ENDPOINT:Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer. SAMPLE SIZE:The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (α) of 5% and a power (1-β) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS:Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter. TRIAL REGISTRATION:The trial is registered at ClinicalTrials.gov (NCT03719547). 10.1136/ijgc-2019-000558
    Which is better for predicting pelvic lymph node metastases in patients with cervical cancer: Fluorodeoxyglucose-positron emission tomography/computed tomography or a sentinel node biopsy? A retrospective observational study. Tanaka Tomohito,Sasaki Shun,Tsuchihashi Hiromitsu,Terai Yoshito,Yamamoto Kazuhiro,Yamada Takashi,Ohmichi Masahide Medicine Systematic pelvic lymph node resection may not be needed for patients with cervical cancer, especially in the early stage, if the pre- or intraoperative diagnosis of lymph node status is correct. The aim of this study was to evaluate the diagnostic accuracy of pelvic lymph node metastasis for fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) and sentinel node biopsy (SNB) of cervical cancer patients.Forty-eight patients with cervical cancer were imaged with FDG PET/CT before radical hysterectomy and underwent an SNB followed by systematic pelvic lymph node dissection. The diagnostic accuracy for predicting pelvic node metastases for FDG PET/CT and SNB compared with the ultimate histologic status was analyzed.Among 96 hemi-pelvises (HPs) in 48 patients, pelvic lymph node metastases were obtained in 12 HPs. The sensitivity of pelvic node metastases for FDG PET/CT and SNB was 8.3% and 75.0%, respectively. The specificity for FDG PET/CT and SNB was 97.6% and 94.0%, respectively. The negative predictive value for FDG-PET/CT and SNB was 88.2% and 100%, respectively.SNB is more suitable for detecting pelvic node metastases than FDG PET/CT. The omission of systematic pelvic lymphadenectomy should be considered based on the findings of SNB, not FDG PET/CT. 10.1097/MD.0000000000010410
    Utility of PET-CT to evaluate retroperitoneal lymph node metastasis in advanced cervical cancer: Results of ACRIN6671/GOG0233 trial. Atri Mostafa,Zhang Zheng,Dehdashti Farrokh,Lee Susanna I,Ali Shamshad,Marques Helga,Koh Wui-Jin,Moore Kathleen,Landrum Lisa,Kim Jae Weon,DiSilvestro Paul,Eisenhauer Eric,Schnell Frederick,Gold Michael Gynecologic oncology OBJECTIVE:To assess if FDG PET combined with diagnostic CT improves diagnostic CT accuracy to detect lymph node (LN) metastasis in advanced cervical cancer. METHODS:A prospective HIPAA compliant ACRIN/GOG multicenter trial was conducted. Patients underwent concurrent diagnostic contrast-enhanced CT (DCT) and PET and pelvic/abdominal lymphadenectomy. Seven independent blinded readers reviewed PET-DCT and DCT one-month apart. Reference standard was surgically removed LN pathology. Accuracy values were calculated at participant level, correlating abdominal (right and left para-aortic/common iliac) and pelvic (right and left external iliac/obturator) LN regions with pathology, respecting laterality. Reader average sensitivities/specificities of PET-DCT vs. DCT were compared with generalized linear mixed models, and AUCs with Obuchowski's method. RESULTS:One hundred fifty-three patients had PET-DCT and pathology. Forty-three of 153 patients had metastasis to abdominal LNs. Sample size calculation required review of the first 40 abdominal positive and 40 randomly selected abdominal negative studies. Patients were 24 to 74years (48.9±10.6) old. Mean sensitivities of PET-DCT/DCT for detection of LN metastasis in abdomen were 0.50 (CI: 0.44, 0.56) and 0.42 (CI: 0.36, 0.48) (p=0.052) and in pelvis 0.83 (CI: 0.78, 0.87) and 0.79 (CI: 0.73, 0.83) (p=0.15). Corresponding specificities were 0.85 (CI: 0.80, 0.89) and 0.89 (CI: 0.84, 0.92) (p=0.21) and 0.63 (CI: 0.54, 0.70) and 0.62 (CI: 0.53, 0.69) (p=0.83). Mean AUC values were 0.70 (CI: 0.61, 0.79) and 0.68 (CI: 0.59, 0.77) (p=0.43) and 0.80 (CI: 0.71, 0.88) and 0.76 (CI: 0.67, 0.85) (p=0.21) respectively. CONCLUSION:Addition of PET to DCT resulted in statistically borderline increase in sensitivity to detect LN metastasis in abdomen in advanced cervical cancer. 10.1016/j.ygyno.2016.05.002
    A phase II study of postoperative concurrent carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy followed by consolidation chemotherapy in surgically treated cervical cancer patients with positive pelvic lymph nodes. Mabuchi Seiji,Isohashi Fumiaki,Yokoi Takeshi,Takemura Masahiko,Yoshino Kiyoshi,Shiki Yasuhiko,Ito Kimihiko,Enomoto Takayuki,Ogawa Kazuhiko,Kimura Tadashi Gynecologic oncology OBJECTIVES:A phase II study was conducted to evaluate the efficacy and toxicity of carboplatin plus paclitaxel (TC)-based postoperative concurrent chemoradiotherapy (CCRT) followed by TC-based consolidation chemotherapy in surgically-treated early-stage cervical cancer patients. METHODS:Women with surgically-treated early-stage cervical cancer with positive pelvic lymph nodes were eligible for this study. The patients were postoperatively treated with pelvic intensity modulated radiotherapy (50.4Gy) and concurrent weekly carboplatin (AUC: 2) and paclitaxel (35mg/m(2)) (TC-based CCRT). Three cycles of consolidation chemotherapy involving carboplatin (AUC: 5) and paclitaxel (175mg/m(2)) were administered after TC-based CCRT. RESULTS:Thirty-one patients were enrolled and treated. Overall, the treatment was well tolerated, and 26 patients (83.9%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non-hematological toxicity. After a median follow-up period of 36.5months, 2 patients (6.5%) had developed recurrent disease. The patients' estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 88.5% and 93.8%, respectively. In comparisons with historical control groups, TC-based CCRT followed by TC-based consolidation chemotherapy was found to be significantly superior to CCRT involving a single platinum agent in terms of PFS (p=0.026) and significantly superior to extended-field radiotherapy in terms of both PFS (p=0.0004) and OS (p=0.034). CONCLUSIONS:In women with surgically treated early-stage cervical cancer, pelvic TC-based CCRT followed by TC-based consolidation chemotherapy is feasible and highly effective. Future randomized trials are needed to verify the efficacy of this regimen. 10.1016/j.ygyno.2016.02.011
    Prognostic significance of lymph node ratio in node-positive cervical cancer patients. Joo Ji Hyeon,Kim Young Seok,Nam Joo-Hyun Medicine To determine whether the pelvic lymph node ratio (LNR) has significant prognostic value for survival and disease recurrence in node-positive, early stage cervical cancer patients.The medical records of 872 consecutive women who received postoperative adjuvant chemoradiotherapy were reviewed. Of these, 397 women with pathologically proven lymph nodal metastasis were included in this analysis and categorized into 3 groups according to their LNR: low (<0.1, n = 251), intermediate (0.1-0.4, n = 121), and high (>0.4, n = 25). The association between LNR and oncological outcome was evaluated using the Kaplan-Meier method and multivariate analysis.A total of 13,491 LNs were retrieved from 397 women, with a median harvest of 32 nodes per patient. There was a strong positive correlation between the number of metastatic LNs and LNR (r = 0.83, P < .01). With a median follow-up duration of 48 months, the 5-year overall survival (OS) and disease-free survival (DFS) rates were 73% and 67%, respectively. The OS and DFS curves among the pelvic LNR groups significantly differed: the 5-year OS rates of the low, intermediate, and high pelvic LNR groups were 83%, 66%, and 17% (P < .01), and the 5-year DFS rates were 77%, 56%, and 20% (P < .01), respectively.LNR is an important prognostic factor for survival outcomes in patients with uterine cervical cancer who underwent radical hysterectomy followed by adjuvant chemoradiotherapy. 10.1097/MD.0000000000011711
    Incidence of adverse events in minimally invasive vs open radical hysterectomy in early cervical cancer: results of a randomized controlled trial. Obermair Andreas,Asher Rebecca,Pareja Rene,Frumovitz Michael,Lopez Aldo,Moretti-Marques Renato,Rendon Gabriel,Ribeiro Reitan,Tsunoda Audrey,Behan Vanessa,Buda Alessandro,Bernadini Marcus Q,Zhao Hongqin,Vieira Marcelo,Walker Joan,Spirtos Nick M,Yao Shuzhong,Chetty Naven,Zhu Tao,Isla David,Tamura Mariano,Nicklin James,Robledo Kristy P,Gebski Val,Coleman Robert L,Salvo Gloria,Ramirez Pedro T American journal of obstetrics and gynecology BACKGROUND:Standard treatment of early cervical cancer involves a radical hysterectomy and retroperitoneal lymph node dissection. The existing evidence on the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer is either nonrandomized or retrospective. OBJECTIVE:The purpose of this study was to compare the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer. STUDY DESIGN:The Laparoscopic Approach to Carcinoma of the Cervix trial was a multinational, randomized noninferiority trial that was conducted between 2008 and 2017, in which surgeons from 33 tertiary gynecologic cancer centers in 24 countries randomly assigned 631 women with International Federation of Gynecology and Obstetrics 2009 stage IA1 with lymph-vascular invasion to IB1 cervical cancer to undergo minimally invasive (n = 319) or open radical hysterectomy (n = 312). The Laparoscopic Approach to Carcinoma of the Cervix trial was suspended for enrolment in September 2017 because of an increased risk of recurrence and death in the minimally invasive surgery group. Here we report on a secondary outcome measure: the incidence of intra- and postoperative adverse events within 6 months after surgery. RESULTS:Of 631 randomly assigned patients, 536 (85%; mean age, 46.0 years) met inclusion criteria for this analysis; 279 (52%) underwent minimally invasive radical hysterectomy, and 257 (48%) underwent open radical hysterectomy. Of those, 300 (56%), 91 (16.9%), and 69 (12.8%) experienced at least 1 grade ≥2 or ≥3 or a serious adverse event, respectively. The incidence of intraoperative grade ≥2 adverse events was 12% (34/279 patients) in the minimally invasive group vs 10% (26/257) in the open group (difference, 2.1%; 95% confidence interval, -3.3 to 7.4%; P=.45). The overall incidence of postoperative grade ≥2 adverse events was 54% (152/279 patients) in the minimally invasive group vs 48% (124/257) in the open group (difference, 6.2%; 95% confidence interval, -2.2 to 14.7%; P=.14). CONCLUSION:For early cervical cancer, the use of minimally invasive compared with open radical hysterectomy resulted in a similar overall incidence of intraoperative or postoperative adverse events. 10.1016/j.ajog.2019.09.036
    Long-term oncological outcomes of minimally invasive radical hysterectomy for early-stage cervical cancer: A retrospective, single-institutional study in the wake of the LACC trial. Kanno Kiyoshi,Andou Masaaki,Yanai Shiori,Toeda Mitsuru,Nimura Ryo,Ichikawa Fuyuki,Teishikata Yasuhiro,Shirane Terumi,Sakate Shintaro,Kihira Tomohisa,Hamasaki Yoichiro,Sawada Mari,Shirane Akira,Ota Yoshiaki The journal of obstetrics and gynaecology research AIM:The objective of this study was to investigate the long-term oncological outcomes of minimally invasive radical hysterectomy (MIRH) for the treatment of early-stage cervical cancer retrospectively in the wake of the laparoscopic approach to cervical cancer (LACC) trial. METHODS:A total of 109 patients with stage IA1 with lymphovascular space involvement, IA2, and IB1 cervical cancers were included in this study. The surgical and oncological outcomes were retrospectively evaluated. All patients underwent type C MIRH with a no-touch isolation technique for cervical tumor. RESULTS:The median number of resected pelvic lymph nodes was 36 (range, 14-94), and 10 patients (9.2%) had positive nodes. One patient (0.9%) had positive surgical margins. Forty-six patients (42%) underwent adjuvant therapy. The median follow-up time was 73 months (range, 30-146 months). Five patients (4.6%) developed recurrent disease, and 3 patients (2.8%) died of cervical cancer. The 5-year disease-free survival and overall survival rates were 96.3% and 97.2%, respectively. A comparison between patients with tumor diameter ≤ 2 cm (n = 59) and those with tumor diameter > 2 cm (n = 50) did not identify any significant differences, with 5-year disease-free survival 96.6% versus 94.0% and 5-year overall survival 98.3% versus 96.0%, respectively. CONCLUSION:In this retrospective study, MIRH with a no-touch isolation technique for stage IA to IB1 cervical cancer was a safe approach in terms of oncological outcomes. However, every surgeon who treats early-stage cervical cancer should inform each patient of the results of the LACC trial because it has an exceedingly high impact. 10.1111/jog.14116
    Risk stratification models for para-aortic lymph node metastasis and recurrence in stage IB-IIB cervical cancer. Matsuo Koji,Shimada Muneaki,Saito Tsuyoshi,Takehara Kazuhiro,Tokunaga Hideki,Watanabe Yoh,Todo Yukiharu,Morishige Ken Ichirou,Mikami Mikio,Sugiyama Toru Journal of gynecologic oncology OBJECTIVE:To examine the surgical-pathological predictors of para-aortic lymph node (PAN) metastasis at radical hysterectomy, and for PAN recurrence among women who did not undergo PAN dissection at radical hysterectomy. METHODS:This is a retrospective analysis of a nation-wide cohort study of surgically-treated stage IB-IIB cervical cancer (n=5,620). Multivariate models were used to identify independent surgical-pathological predictors for PAN metastasis/recurrence. RESULTS:There were 120 (2.1%) cases of PAN metastasis at surgery with parametrial involvement (adjusted odds ratio [aOR]=1.65), deep stromal invasion (aOR=2.61), ovarian metastasis (aOR=3.10), and pelvic nodal metastasis (single-node aOR=5.39 and multiple-node aOR=33.5, respectively) being independent risk factors (all, p<0.05). Without any risk factors, the incidence of PAN metastasis was 0.9%, while women exhibiting certain risk factor patterns (>20% of the study population) had PAN metastasis incidences of ≥4%. Among 4,663 clinically PAN-negative cases at surgery, PAN recurrence was seen in 195 (4.2%) cases that was significantly higher than histologically PAN-negative cases (2.5%, p=0.046). In clinically PAN-negative cases, parametrial involvement (adjusted hazard ratio [aHR]=1.67), lympho-vascular space invasion (aHR=1.95), ovarian metastasis (aHR=2.60), and pelvic lymph node metastasis (single-node aHR=2.49 and multiple-node aHR=8.11, respectively) were independently associated with increased risk of PAN recurrence (all, p<0.05). Without any risk factors, 5-year PAN recurrence risk was 0.8%; however, women demonstrating certain risk factor patterns (>15% of the clinically PAN-negative population) had 5-year PAN recurrence risks being ≥8%. CONCLUSION:Surgical-pathological risk factors proposed in this study will be useful to identify women with increased risk of PAN metastasis/recurrence. 10.3802/jgo.2018.29.e11
    Does small volume metastatic lymph node disease affect long-term prognosis in early cervical cancer? Nica Andra,Gien Lilian T,Ferguson Sarah Elizabeth,Covens Allan International journal of gynecological cancer : official journal of the International Gynecological Cancer Society INTRODUCTION:As sentinel lymph node biopsy is evolving to an accepted standard of care, clinicians are being faced with more frequent cases of small volume nodal metastatic disease. The objective of this study is to describe the management and to measure the effect on recurrence rates of nodal micrometastasis and isolated tumor cells in patients with early stage cervical cancer at two high-volume centers. METHODS:We conducted a review of prospectively collected patients with surgically treated cervical cancer who were found to have micrometastasis or isolated tumor cells on ultrastaging of the sentinel lymph node. Our practice is to follow patients for ≥5 years post-operatively either at our center or another cancer center closer to home. RESULTS:Nineteen patients with small volume nodal disease were identified between 2006 and 2018. Median follow-up was 62 months. Ten (53%) had nodal micrometastatic disease, while nine (47%) had isolated tumor cells detected in the sentinel lymph node. Seven patients (37%) underwent completion pelvic lymphadenectomy and four of them also had para-aortic lymphadenectomy; there were no positive non-sentinel lymph nodes. The majority (74%) received adjuvant treatment, mostly driven by tumor factors. We observed two recurrences. Recurrence-free survival was comparable with historical cohorts of node negative patients, and adjuvant treatment did not seem to impact the recurrence rate (p=0.5). CONCLUSION:Given the uncertainties around the prognostic significance of small volume nodal disease in cervical cancer, a large proportion of patients receive adjuvant treatment. We found no positive non-sentinel lymph nodes, suggesting that pelvic lymphadenectomy or para-aortic lymphadenectomy may not be of benefit in patients diagnosed with small volume nodal metastases. Recurrence-free survival in this group did not seem to be affected. However, given the small numbers of patients and lack of level 1 evidence, decisions should be individualized in accordance with patient preferences and tumor factors. 10.1136/ijgc-2019-000928