Palliative resection of the primary tumor is associated with improved overall survival in incurable stage IV colorectal cancer: A nationwide population-based propensity-score adjusted study in the Netherlands.
't Lam-Boer Jorine,Van der Geest Lydia G,Verhoef Cees,Elferink Marloes E,Koopman Miriam,de Wilt Johannes H
International journal of cancer
As the value of palliative primary tumor resection in stage IV colorectal cancer (CRC) is still under debate, the purpose of this population-based study was to investigate if palliative primary tumor resection as the initial treatment after diagnosis was associated with improved overall survival. All patients with stage IV colorectal adenocarcinoma (2008-2011) were selected from the Netherlands Cancer Registry, and patients undergoing treatment with curative intent (i.e., metastasectomy, radiofrequency ablation and/or hyperthermic intraperitoneal chemotherapy), or best supportive care were excluded. After propensity score matching, a multivariable Cox proportional hazard model was performed to determine the association between treatment strategy and mortality. From a total group of 10,371 patients with stage IV CRC, 2,746 patients (26%) underwent an elective palliative resection of the primary tumor, whether or not followed by systemic therapy, and 3,345 patients (32%) were initially treated with palliative systemic therapy. After propensity score matching, median overall survival in these groups was 17.2 months (95% CI 16.3-18.1) and 11.5 months (95% CI 11.0-12.0), respectively. In Cox regression analysis, primary tumor resection was significantly associated with improved overall survival (hazard ratio of death = 0.44 [95% CI 0.35-0.55], p < 0.001). This large population-based study shows an overall survival benefit for patients with incurable stage IV CRC who underwent primary tumor resection as the initial treatment after diagnosis, compared to patients who started systemic therapy with the primary tumor in situ. This result is an argument in favor of resection of the primary tumor, even when patients have little to no symptoms.
10.1002/ijc.30240
Prognostic Relevance of Palliative Primary Tumor Removal in 37,793 Metastatic Colorectal Cancer Patients: A Population-Based, Propensity Score-Adjusted Trend Analysis.
Tarantino Ignazio,Warschkow Rene,Worni Mathias,Cerny Thomas,Ulrich Alexis,Schmied Bruno M,Güller Ulrich
Annals of surgery
OBJECTIVE:To assess whether palliative primary tumor resection in colorectal cancer patients with incurable stage IV disease is associated with improved survival. BACKGROUND:There is a heated debate regarding whether or not an asymptomatic primary tumor should be removed in patients with incurable stage IV colorectal disease. METHODS:Stage IV colorectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 1998 and 2009. Patients undergoing surgery to metastatic sites were excluded. Overall survival and cancer-specific survival were compared between patients with and without palliative primary tumor resection using risk-adjusted Cox proportional hazard regression models and stratified propensity score methods. RESULTS:Overall, 37,793 stage IV colorectal cancer patients were identified. Of those, 23,004 (60.9%) underwent palliative primary tumor resection. The rate of patients undergoing palliative primary cancer resection decreased from 68.4% in 1998 to 50.7% in 2009 (P < 0.001). In Cox regression analysis after propensity score matching primary cancer resection was associated with a significantly improved overall survival [hazard ratio (HR) of death = 0.40, 95% confidence interval (CI) = 0.39-0.42, P < 0.001] and cancer-specific survival (HR of death = 0.39, 95% CI = 0.38-0.40, P < 0.001). The benefit of palliative primary cancer resection persisted during the time period 1998 to 2009 with HRs equal to or less than 0.47 for both overall and cancer-specific survival. CONCLUSIONS:On the basis of this population-based cohort of stage IV colorectal cancer patients, palliative primary tumor resection was associated with improved overall and cancer-specific survival. Therefore, the dogma that an asymptomatic primary tumor never should be resected in patients with unresectable colorectal cancer metastases must be questioned.
10.1097/SLA.0000000000000860
Influence of primary tumor location and resection on survival in metastatic colorectal cancer.
Tharin Zoé,Blanc Julie,Alaoui Ikram Charifi,Bertaut Aurélie,Ghiringhelli François
World journal of gastrointestinal oncology
BACKGROUND:Patients with right sided colorectal cancer are known to have a poorer prognosis than patients with left sided colorectal cancer, whatever the cancer stage. To this day, primary tumor resection (PTR) is still controversial in a metastatic, non resectable setting. AIM:To explore the survival impact of PTR in patients with metastatic colorectal cancer (mCRC) depending on PTL. METHODS:We retrospectively collected data from all consecutive patients treated for mCRC at the Centre Georges Francois Leclerc Hospital. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of PTR on survival. We then evaluated the association between PTL and overall survival among patients who previously underwent or did not undergo PTR. A propensity score was performed to match cohorts. RESULTS:Four hundred and sixty-six patients were included. A total of 153 (32.8%) patients had unresected synchronous mCRC and 313 (67.2%) patients had resected synchronous mCRC. The number of patients with right colic cancer, left colic cancer and rectal cancer was respectively 174 (37.3%), 203 (43.6%) and 89 (19.1%). In the multivariate analysis only PTL, PTR, resection of hepatic and or pulmonary metastases and the use of oxaliplatin, EGFR inhibitors or bevacizumab throughout treatment were associated to higher overall survival rates. Survival evaluation depending on PTR and PTL found that PTR improved the prognosis of both left and right sided mCRC. Results were confirmed by using a weighted propensity score. CONCLUSION:In mCRC, PTR seems to confer a higher survival rate to patients whatever the PTL.
10.4251/wjgo.v12.i11.1296
Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival.
Hu Chung-Yuan,Bailey Christina E,You Y Nancy,Skibber John M,Rodriguez-Bigas Miguel A,Feig Barry W,Chang George J
JAMA surgery
IMPORTANCE:With the advent of effective modern chemotherapeutic and biologic agents, primary tumor resection for patients with stage IV colorectal cancer (CRC) may not be routinely necessary. OBJECTIVE:To evaluate the secular patterns of primary tumor resection use in stage IV CRC in the United States. DESIGN, SETTING, AND PARTICIPANTS:A retrospective cohort study using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results CRC registry. Demographic and clinical factors were compared for 64,157 patients diagnosed with stage IV colon or rectal cancer from January 1, 1988, through December 31, 2010, who had undergone primary tumor resection and those who had not. Rates of primary tumor resection and median relative survival were calculated for each year. Joinpoint regression analysis was used to determine when a significant change in trend in the primary tumor resection rate had occurred. Logistic regression analysis was used to assess factors associated with primary tumor resection. MAIN OUTCOMES AND MEASURES:Difference in primary tumor resection rates over time. RESULTS:Of the 64,157 patients with stage IV CRC, 43,273 (67.4%) had undergone primary tumor resection. The annual rate of primary tumor resection decreased from 74.5% in 1988 to 57.4% in 2010 (P<.001), and a significant annual percentage change occurred between 1998-2001 and 2001-2010 (-0.41% vs -2.39%; P<.001). Factors associated with primary tumor resection were age younger than 50 years, female sex, being married, higher tumor grade, and presence of colon tumors. Median relative survival rate improved from 8.6% in 1988 to 17.8% in 2009 (P<.001); the annual percentage change was 2.18% in 1988-2001 and 5.43% in 1996-2009 (P<.001). CONCLUSIONS AND RELEVANCE:The majority of patients with stage IV CRC had undergone primary tumor resection but, beginning in 2001, a trend toward fewer primary tumor resections was seen. Despite the decreasing primary tumor resection rate, patient survival rates improved. However, primary tumor resection may still be overused, and current treatment practices lag behind evidence-based treatment guidelines.
10.1001/jamasurg.2014.2253
Resection of the Primary Tumor in Stage IV Colorectal Cancer: When Is It Necessary?
Feo Leandro,Polcino Michael,Nash Garrett M
The Surgical clinics of North America
Management of metastatic colorectal cancer requires accurate staging and multidisciplinary evaluation, leading to a consensus treatment plan with the ultimate goal of increasing survival and improving the quality of life, while taking into consideration the patient's performance status, disease burden, and goals of care. Since the introduction of multidrug chemotherapeutic regimens, survival of patients with metastatic colorectal cancer has improved. Many patients with unresectable disease are undergoing surgery for asymptomatic primary tumors despite evidence that it is usually a futile intervention. Palliative measures for local control of the primary tumor include colonic stents, laser therapy, and fulguration.
10.1016/j.suc.2017.01.012
Comparative effectiveness of primary tumor resection in patients with stage IV colon cancer.
Alawadi Zeinab,Phatak Uma R,Hu Chung-Yuan,Bailey Christina E,You Y Nancy,Kao Lillian S,Massarweh Nader N,Feig Barry W,Rodriguez-Bigas Miguel A,Skibber John M,Chang George J
Cancer
BACKGROUND:Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR. METHODS:An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used. RESULTS:In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06). CONCLUSIONS:Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society.
10.1002/cncr.30230
Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? A pooled analysis of individual data from four randomised trials.
Faron Matthieu,Pignon Jean-Pierre,Malka David,Bourredjem Abderrahmane,Douillard Jean-Yves,Adenis Antoine,Elias Dominique,Bouché Olivier,Ducreux Michel
European journal of cancer (Oxford, England : 1990)
OBJECTIVE:To evaluate the impact on survival of primary tumour resection in patients with unresectable synchronous metastases from colorectal cancer (CRC). SUMMARY BACKGROUND DATA:Primary tumour resection in this setting remains controversial. PATIENTS AND METHODS:We retrieved individual data of 1155 patients with metastatic CRC included in four first-line chemotherapy trials: Fédération Francophone de Cancérologie Digestive (FFCD)-9601, FFCD-2000-05, Actions Concertées dans les cancers COloRectaux et Digestifs (ACCORD)-13, and ML-16987. Patients with unresectable synchronous metastases were eligible for this study. We used univariate and multivariate analyses (Cox models stratified on the trial) to assess the impact of primary tumour resection and other potential prognostic variables on overall survival (OS) (the primary endpoint). RESULTS:Amongst the 1155 patients, 810 patients met the inclusion criteria and 59% (n = 478) underwent resection of their primary tumour, prior to trial entry (resection group). Compared to patients in the non-resection group (n =3 32 [41%]), those in the resection group were more likely to have a colonic primary, lower baseline carcinoembryonic antigen (CEA) and alkaline phosphatase levels, and normal white-blood-cell count (p < 0.001 each). Primary tumour resection was independently associated to better OS in multivariate analysis (hazard ratio (HR), 0.63 [0.53-0.75]; p < 0.001, with a more favourable impact of resection on OS in case of rectal primary and low CEA level. Primary tumour resection was also independently associated to a better progression-free survival in multivariate analysis (HR, 0.82 [0.70-0.95]; p < 0.001). CONCLUSION:Primary tumour resection was independently associated to a better OS in patients with CRC and unresectable synchronous metastases.
10.1016/j.ejca.2014.10.023
The Role of Primary Tumor Resection in Colorectal Cancer Patients with Asymptomatic, Synchronous, Unresectable Metastasis: A Multicenter Randomized Controlled Trial.
Park Eun Jung,Baek Jeong-Heum,Choi Gyu-Seog,Park Won Cheol,Yu Chang Sik,Kang Sung-Bum,Min Byung Soh,Kim Jae Hwang,Kim Hyeong Rok,Lee Bong Hwa,Oh Jae Hwan,Jeong Seung-Yong,Jung Minkyu,Ahn Joong Bae,Baik Seung Hyuk
Cancers
We aimed to assess the survival benefits of primary tumor resection (PTR) followed by chemotherapy in patients with asymptomatic stage IV colorectal cancer with asymptomatic, synchronous, unresectable metastases compared to those of upfront chemotherapy alone. This was an open-label, prospective, randomized controlled trial (ClnicalTrials.gov Identifier: NCT01978249). From May 2013 to April 2016, 48 patients (PTR, = 26; upfront chemotherapy, = 22) diagnosed with asymptomatic colorectal cancer with unresectable metastases in 12 tertiary hospitals were randomized (1:1). The primary endpoint was two-year overall survival. The secondary endpoints were primary tumor-related complications, PTR-related complications, and rate of conversion to resectable status. The two-year cancer-specific survival was significantly higher in the PTR group than in the upfront chemotherapy group (72.3% vs. 47.1%; = 0.049). However, the two-year overall survival rate was not significantly different between the PTR and upfront chemotherapy groups (69.5% vs. 44.8%, = 0.058). The primary tumor-related complication rate was 22.7%. The PTR-related complication rate was 19.2%, with a major complication rate of 3.8%. The rates of conversion to resectable status were 15.3% and 18.2% in the PTR and upfront chemotherapy groups. While PTR followed by chemotherapy resulted in better two-year cancer-specific survival than upfront chemotherapy, the improvement in the two-year overall survival was not significant.
10.3390/cancers12082306
The role of primary tumor resection in colorectal cancer patients with asymptomatic, synchronous unresectable metastasis: Study protocol for a randomized controlled trial.
Kim Chang Woo,Baek Jeong-Heum,Choi Gyu-Seog,Yu Chang Sik,Kang Sung Bum,Park Won Cheol,Lee Bong Hwa,Kim Hyeong Rok,Oh Jae Hwan,Kim Jae-Hwang,Jeong Seung-Yong,Ahn Jung Bae,Baik Seung Hyuk
Trials
BACKGROUND:Approximately 20 % of all patients with colorectal cancer are diagnosed as having Stage IV cancer; 80 % of these present with unresectable metastatic lesions. It is controversial whether chemotherapy with or without primary tumor resection (PTR) is effective for the treatment of patients with colorectal cancer with unresectable metastasis. Primary tumor resection could prevent tumor-related complications such as intestinal obstruction, perforation, bleeding, or fistula. Moreover, it may be associated with an increase in overall survival. However, surgery delays the use of systemic chemotherapy and affects the systemic spread of malignancy. METHODS/DESIGN:Patients with colon and upper rectal cancer patients with asymptomatic, synchronous, unresectable metastasis will be included after screening. They will be randomized and assigned to receive chemotherapy with or without PTR. The primary endpoint measure is 2-year overall survival rate and the secondary endpoint measures are primary tumor-related complications, quality of life, surgery-related morbidity and mortality, interventions with curative intent, chemotherapy-related toxicity, and total cost until death or study closing day. The authors hypothesize that the group receiving PTR following chemotherapy would show a 10 % improvement in 2-year overall survival, compared with the group receiving chemotherapy alone. The accrual period is 3 years and the follow-up period is 2 years. Based on the inequality design, a two-sided log-rank test with α-error of 0.05 and a power of 80 % was conducted. Allowing for a drop-out rate of 10 %, 480 patients (240 per group) will need to be recruited. Patients will be followed up at every 3 months for 3 years and then every 6 months for 2 years after the last patient has been randomized. DISCUSSION:This randomized controlled trial aims to investigate whether PTR with chemotherapy shows better overall survival than chemotherapy alone for patients with asymptomatic, synchronous unresectable metastasis. This trial is expected to provide evidence so support clear treatment guidelines for patients with colorectal cancer with asymptomatic, synchronous unresectable metastasis. TRIAL REGISTRATION:Clinicaltrials.gov NCT01978249 .
10.1186/s13063-016-1164-0
Non-resection versus resection for an asymptomatic primary tumour in patients with unresectable stage IV colorectal cancer.
Cirocchi Roberto,Trastulli Stefano,Abraha Iosief,Vettoretto Nereo,Boselli Carlo,Montedori Alessandro,Parisi Amilcare,Noya Giuseppe,Platell Cameron
The Cochrane database of systematic reviews
BACKGROUND:In a majority of patients with stage IV colorectal cancer, the metastatic disease is not resectable and the focus of management is on how best to palliate the patient. How to manage the primary tumour is an important part of palliation. A small proportion of these patients present with either obstructing or perforating cancers and require urgent surgical care. However, a majority are relatively asymptomatic from their primary cancer. Chemotherapy has been shown to prolong survival in this group of patients, and a majority of patients would be treated this way. Nonetheless, A recent meta-analysis (Stillwell 2010) suggests an improved overall survival and reduced requirement for emergency surgery in those patients who undergo primary tumour resection. This review was also able to quantify the mortality and morbidity associated with surgery to remove the primary. OBJECTIVES:To determine if there is an improvement in overall survival following resection of the primary cancer in patients with unresectable stage IV colorectal cancer and an asymptomatic primary who are treated with chemo/radiotherapy. SEARCH METHODS:In January 2012 we searched for published randomised and non-randomised controlled clinical trials without language restrictions using the following electronic databases: CENTRAL (the Cochrane Library (latest issue)), MEDLINE (1966 to date), EMBASE (1980 to date), Science Citation Index (1981 to date), ISI Proceedings (1990 to date), Current Controlled Trials MetaRegister (latest issue), Zetoc (latest issue) and CINAHL (1982 to date). SELECTION CRITERIA:Randomised controlled trials and non-randomised controlled studies evaluating the influence on overall survival of primary tumour resection versus no resection in asymptomatic patients with unresectable stage IV colorectal cancer who are treated with palliative chemo/radiotherapy. DATA COLLECTION AND ANALYSIS:We conducted the review according to the recommendations of The Cochrane Collaboration and the Cochrane Colorectal Group. "Review Manager 5" software was used. MAIN RESULTS:A total of 798 studies were identified following the initial search. No published or unpublished randomised controlled trials comparing primary tumour resection versus no resection in asymptomatic patients with unresectable stage IV colorectal cancer who were treated with chemo/radiotherapy were identified. Seven non-randomised studies, potentially eligible for inclusion, were identified: 2 case-matched studies, 2 CCTs and 3 retrospective cohort studies. Overall, these trials included 1.086 patients (722 patients treated with primary tumour resection, and 364 patients managed first with chemotherapy and/or radiotherapy). AUTHORS' CONCLUSIONS:Resection of the primary tumour in asymptomatic patients with unresectable stage IV colorectal cancer who are managed with chemo/radiotherapy is not associated with a consistent improvement in overall survival. In addition, resection does not significantly reduce the risk of complications from the primary tumour (i.e. obstruction, perforation or bleeding). Yet there is enough doubt with regard to the published literature to justify further clinical trials in this area. The results from an ongoing high quality randomised controlled trial will help to answer this question.
10.1002/14651858.CD008997.pub2
Palliative excisional surgery for primary colorectal cancer in patients with incurable metastatic disease. Is there a survival benefit? A systematic review.
Anwar S,Peter M B,Dent J,Scott N A
Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland
AIM:Patients with stage IV colorectal cancer with unresectable metastases can either receive chemotherapy or palliative resection of the primary lesion. In the absence of any randomized data the choice of initial treatment in stage IV colorectal cancer is not based on firm evidence. METHOD:A search of MEDLINE, Pubmed, Embase and the Cochrane Library database was performed from 1980 to 2010 for studies comparing palliative resection in stage IV colorectal cancer with other treatment modalities. Audits and observational studies were excluded. Median survival was the primary outcome measure. The morbidity and mortality of surgical and nonsurgical treatments were compared. RESULTS:Twenty-one studies (no randomized controlled trials) were identified. Most demonstrated a survival benefit for patients who underwent palliative resection. Multivariate analysis indicates that tumour burden and performance status are both major independent prognostic variables. Selection bias, incomplete follow up and nonstandardized reporting of complications make the data difficult to interpret. CONCLUSION:The studies indicate that there may be a survival benefit for primary resection of colorectal cancer in stage IV disease. The findings suggest that resection of the primary tumour should be based on tumour burden and performance status rather than on the presence or absence of symptoms alone.
10.1111/j.1463-1318.2011.02817.x
Prognostic value of primary tumour resection in synchronous metastatic colorectal cancer: Individual patient data analysis of first-line randomised trials from the ARCAD database.
van Rooijen K L,Shi Q,Goey K K H,Meyers J,Heinemann V,Diaz-Rubio E,Aranda E,Falcone A,Green E,de Gramont A,Sargent D J,Punt C J A,Koopman M
European journal of cancer (Oxford, England : 1990)
Indication for primary tumour resection (PTR) in asymptomatic metastatic colorectal cancer (mCRC) patients is unclear. Previous retrospective analyses suggest a survival benefit for patients who underwent PTR. The aim was to evaluate the prognostic value of PTR in patients with synchronous mCRC by analysis of recent large RCTs including systemic therapy with modern targeted agents. Individual patient data (IPD) of 3423 patients enrolled into 8 randomised controlled trials (RCTs) with first-line systemic therapy in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analysed. The number of patients with unresected synchronous mCRC, resected synchronous mCRC and metachronous mCRC was 710 (21%), 1705 (50%) and 1008 (29%), respectively. Adjusting for age, gender, performance status (PS) and prior chemotherapy, the unresected group had a significantly worse median overall survival (16.4 m) compared with the synchronous resected (22.2 m; hazard ratio [HR] 1.60, 95% CI 1.43-1.78) and metachronous (22.4 m; HR 1.81, 95% CI 1.58-2.07) groups. Similarly, median progression-free survival was significantly worse for the unresected group compared with the synchronous resected (HR 1.31, 95% CI 1.19-1.44) and metachronous (HR 1.47, 95% CI 1.30-1.66) groups. In a multivariate analysis, the observed associations remained significant. This largest IPD analysis of mCRC trials to date demonstrates an improved survival in synchronous mCRC patients after PTR. These results may be subject to bias since reasons for (non)resection were not available. Until results of ongoing RCTs are available, both upfront PTR followed by systemic treatment and upfront systemic treatment are considered appropriate treatment strategies.
10.1016/j.ejca.2017.12.014
A systematic analysis highlighting deficiencies in reported outcomes for patients with stage IV colorectal cancer undergoing palliative resection of the primary tumour.
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
BACKGROUND:Management of the primary tumour in the presence of unresectable metastatic colorectal cancer (mCRC) is controversial. The role of primary tumour resection (PTR) has been investigated by a number of retrospective cohort studies, with a number on going randomised controlled trials. The aim of this study was to identify the clinical and patient-reported outcomes currently reported in studies that evaluate the role of PTR in mCRC. METHODS:Literature searches were performed in MEDLINE (via OvidSP) (1966-June 2017), EMBASE (via OvidSP) and the Cochrane Library using terms related to colorectal cancer and primary tumour resection. All studies documenting outcomes following palliative PTR were included. Eligible articles were assessed using the Risk of Bias In Non-Randomised Studies of Intervention (ROBINS-I) tool. RESULTS:Of 11,209 studies screened, 59 non-randomised studies reporting outcomes on 331,157 patients were included. Patient characteristics regarding performance status and co-morbidity were recorded in 26 (44.1%) and 17 (28.8%) studies. The chemotherapy regime used was reported in 27 (45.8%) studies. The operative setting and the operative approach was reported in 42 (71%) and 14 (23.7%) studies. Post-operative mortality and morbidity were reported in 33 (55.9%) and 35 (59.3%) studies. Overall survival was reported in 49 (83.1%) studies, with 5 different definitions identified. Quality of life was only reported in 1 (1.7%) study. CONCLUSION:This study demonstrates significant heterogeneity in the selection and definition of outcomes reported following PTR in mCRC. There is significant heterogeneity with a significant under-reporting of important outcomes such as treatment related adverse events and patient reported outcomes.
10.1016/j.ejso.2018.06.012
Sixty-Day Mortality of Patients With Metastatic Colorectal Cancer Randomized to Systemic Treatment vs Primary Tumor Resection Followed by Systemic Treatment: The CAIRO4 Phase 3 Randomized Clinical Trial.
JAMA surgery
Importance:The role of primary tumor resection (PTR) in synchronous patients with metastatic colorectal cancer (mCRC) who had unresectable metastases and few or absent symptoms of their primary tumor is unclear. Studying subgroups with low postoperative mortality may identify patients who potentially benefit from PTR. Objective:To determine the difference in 60-day mortality between patients randomized to systemic treatment only vs PTR followed by systemic treatment, and to explore risk factors associated with 60-day mortality. Design, Setting, and Participants:CAIRO4 is a randomized phase 3 trial initiated in 2012 in which patients with mCRC were randomized to systemic treatment only or PTR followed by systemic treatment with palliative intent. This multicenter study was conducted by the Danish and Dutch Colorectal Cancer Group in general and academic hospitals in Denmark and the Netherlands. Patients included between August 2012 and December 2019 with histologically proven colorectal cancer, unresectable metastases, and a primary tumor with few or absent symptoms were eligible. Interventions:Systemic treatment, consisting of fluoropyrimidine-based chemotherapy with bevacizumab vs PTR followed by fluoropyrimidine-based chemotherapy with bevacizumab. Main Outcomes and Measures:The aim of the current analysis was to compare 60-day mortality rates in both treatment arms. A secondary aim was the identification of risk factors for 60-day mortality in the treatment arms. These aims were not predefined in the study protocol. Results:A total of 196 patients were included in the intention-to-treat analysis (112 [57%] men; median [IQR] age, 65 [59-70] years). Sixty-day mortality was 3% (95% CI, 1%-9%) in the systemic treatment arm and 11% (95% CI, 6%-19%) in the PTR arm (P = .03). In a per-protocol analysis, 60-day mortality was 2% (95% CI, 1%-7%) vs 10% (95% CI, 5%-18%; P = .048). Patients with elevated serum levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and/or neutrophils who were randomized to PTR had a significantly higher 60-day mortality than patients without these characteristics. Conclusions and Relevance:Patients with mCRC who were randomized to PTR followed by systemic treatment had a higher 60-day mortality than patients randomized to systemic treatment. Especially patients randomized to the PTR arm with elevated serum levels of lactate dehydrogenase, neutrophils, aspartate aminotransferase, and/or alanine aminotransferase were at high risk of postoperative mortality. Final study results on overall survival have to be awaited. Trial Registration:ClinicalTrials.gov Identifier: NCT01606098.
10.1001/jamasurg.2021.4992
Overcoming the challenges of primary tumor management in patients with metastatic colorectal cancer unresectable for cure and an asymptomatic primary tumor.
Matsumoto Takuya,Hasegawa Suguru,Matsumoto Shigemi,Horimatsu Takahiro,Okoshi Kae,Yamada Masahiro,Kawada Kenji,Sakai Yoshiharu
Diseases of the colon and rectum
BACKGROUND:The management of asymptomatic primary tumor in patients with unresectable metastatic colorectal cancer remains inconsistent. OBJECTIVE:This study aimed to determine the rate of symptom-directed surgery after systemic chemotherapy and to estimate the impact of initial primary tumor resection on survival in patients with unresectable metastatic colorectal cancer and an asymptomatic primary tumor. DESIGN:This was a single-institution, retrospective observational study. SETTINGS:The study was conducted in a tertiary referral hospital. PATIENTS:Between 2005 and 2011, 191 consecutive patients with newly diagnosed stage IV colorectal cancer were identified. Of the 191, we analyzed 94 patients with unresectable, asymptomatic colorectal cancer. MAIN OUTCOME MEASURES:We measured symptom-directed surgery and overall survival. RESULTS:Forty-seven patients with an intact primary tumor received systemic chemotherapy (upfront chemotherapy group), 41 underwent primary tumor resection (upfront primary tumor resection group), and 6 underwent diversion enterostomy as first-line therapy. After excluding the 6 patients undergoing diversion enterostomy before systemic chemotherapy, this left 88 patients for final analysis. Twelve upfront chemotherapy patients required symptom-directed late surgery. Overall, 1-year and 2-year rates of symptom-directed surgery were 19.1% and 26.1%. In patients with nontraversable lesions by colonoscope at diagnosis, 64.3% required late intervention within 1 year. Competing risk regression analysis revealed that only colonoscopic traversability at diagnosis was significantly associated with symptom-directed late surgery (subhazard ratio, 7.9; p = 0.004). Median overall survival time was comparable between the 2 groups at 23.9 months for the upfront primary tumor resection group and 22.6 months for the upfront chemotherapy group (HR, 0.84; 95% CI: 0.51-1.39). LIMITATIONS:This study was limited by its retrospective nature and small sample size. CONCLUSIONS:Approximately 75% of upfront chemotherapy patients with unresectable, asymptomatic stage IV colorectal cancer can be spared initial resection of the primary tumor. Colonoscopic findings of nontraversable lesions at diagnosis may predict the need for late surgical intervention.
10.1097/DCR.0000000000000025
Clinical significance of primary tumor resection in colorectal cancer patients with synchronous unresectable metastasis.
Kim Min Sung,Chung MinKyu,Ahn Joong Bae,Kim Chang Woo,Cho Min Soo,Shin Sang Joon,Baek Se Jin,Hur Hyuk,Min Byung Soh,Baik Seung Hyuk,Kim Nam Kyu
Journal of surgical oncology
BACKGROUND:The aim of this study was to compare the outcomes in colorectal cancer (CRC) patients with synchronous unresectable metastases who received either primary tumor resection (PTR) or chemotherapy as the first treatment and to investigate the clinical course of asymptomatic patients who received chemotherapy as the first treatment. METHODS:We retrospectively analyzed 324 CRC patients with synchronous unresectable metastases. Overall survival (OS) was analyzed for the two groups (upfront PTR group [n = 72] vs. upfront chemotherapy group [n = 252]). Surgical morbidity and mortality were recorded. In the asymptomatic patients who received upfront chemotherapy, the incidences of primary tumor-related complications were analyzed. RESULTS:In patients who underwent PTR as the first treatment, the median OS period was superior to those who received upfront chemotherapy (17.2 vs. 13.6 months, P = 0.002). In the PTR group, surgical morbidity and mortality were 11.6% and 1.9%, respectively. Of the 252 asymptomatic patients, the incidence of primary tumor-related complications was 35%. Emergent surgery was ultimately done in 14% of the 252 patients. CONCLUSION:CRC patients with synchronous unresectable metastases who underwent PTR followed by chemotherapy had significantly longer survival times compared to patients who received chemotherapy as the first treatment.
10.1002/jso.23607
Primary Tumor Resection Plus Chemotherapy Versus Chemotherapy Alone for Colorectal Cancer Patients With Asymptomatic, Synchronous Unresectable Metastases (JCOG1007; iPACS): A Randomized Clinical Trial.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE:It remains controversial whether primary tumor resection (PTR) before chemotherapy improves survival in patients with colorectal cancer (CRC) with asymptomatic primary tumor and synchronous unresectable metastases. PATIENTS AND METHODS:This randomized phase III study investigated the superiority of PTR followed by chemotherapy versus chemotherapy alone in relation to overall survival (OS) in patients with unresectable stage IV asymptomatic CRC and three or fewer unresectable metastatic diseases confined to the liver, lungs, distant lymph nodes, or peritoneum. Chemotherapy regimens of either mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab were decided before study entry. The primary end point was OS, which was analyzed by intention-to-treat. RESULTS:Between June 2012 and September 2019, a total of 165 patients were randomly assigned to either chemotherapy alone (84 patients) or PTR plus chemotherapy (81 patients). When the first interim analysis was performed in September 2019 with 50% (114/227) of the expected events observed among 160 patients at the data cutoff date of June 5, 2019, the Data and Safety Monitoring Committee recommended early termination of the trial because of futility. With a median follow-up of 22.0 months, median OS was 25.9 months (95% CI, 19.9 to 31.5) in the PTR plus chemotherapy arm and 26.7 (95% CI, 21.9 to 32.5) in the chemotherapy-alone arm (hazard ratio, 1.10; 95% CI, 0.76 to 1.59; one-sided = .69). Three postoperative deaths occurred in the PTR plus chemotherapy arm. CONCLUSION:Given that PTR followed by chemotherapy showed no survival benefit over chemotherapy alone, PTR should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases.
10.1200/JCO.20.02447