
Observation With or Without Subsequent Salvage Therapy for Pathologically Node-positive Prostate Cancer With Negative Conventional Imaging: Results From a Large Multicenter Cohort.
European urology open science
Background and objective:More than 10% of patients with negative clinical metastatic status (cN0M0) on conventional imaging for prostate cancer (PCa) harbor lymph node involvement (pN+) at final pathology following radical prostatectomy (RP) and lymphadenectomy. Our aim was to assess outcomes of initial observation for cN0M0 pN+ PCa and identify prognostic factors that may help in clinical decision-making. Methods:We performed a retrospective multicenter study of patients with cN0M0 PCa on conventional imaging (computed tomography and/or magnetic resonance imaging, and a bone scan) who were found to have pN+ disease at RP between 2000 and 2021. Biochemical recurrence (BCR) and systemic progression/recurrence were the primary outcomes. Kaplan-Meier curves and Cox proportional hazards model were used for survival and multivariate analysis. Key findings and limitations:A total of 469 men were included in this retrospective multicenter trial. Median prostate-specific antigen (PSA) was 10.1 ng/ml (interquartile range [IQR] 6.6-18.0). Among these patients, 56% had grade group ≥4, 53.7% had stage ≥pT3b, 42.6% had positive margins, and 19.6% had PSA persistence. The median number of positive nodes and of nodes removed were 1 (IQR 1-3) and 20 (14-28), respectively. At median follow-up of 41 mo, 48.5% experienced BCR. The 5-yr BCR-free survival rate was 31.7% (95% confidence interval [CI] 26.33-37.1%). Salvage treatments were needed in 211 patients and included radiotherapy (RT; = 53), RT + androgen deprivation therapy (ADT; = 88), ADT alone ( = 68), and salvage lymphadenectomy ( = 2). The 5-yr estimated survival rates were 66.3% (95% CI 60.4-72.1) for metastasis-free survival, 97.7% (95% CI 95.5-99.8%) for cancer-specific survival, and 95.3% (95% CI 92.4-98.1%) for overall survival. On multivariable analysis, PSA persistence was an independent predictor of BCR (odds ratio [OR] 51.8, 95% CI 12.2-219.2), exit from observation (OR 8.5, 95% CI 4.4-16.5), and systemic progression (OR 3.0, 95% CI 1.771-4.971). Conclusions:Initial observation in the management of pN+ cN0M0 PCa is feasible and has excellent survival rates in the intermediate term. Patients with worse disease features, especially PSA persistence, have a higher likelihood of recurrence and progression and may be candidates for more aggressive upfront management. Patient summary:We investigated the value of initial observation for men with prostate cancer with negative scan findings for metastasis who were then found to have positive lymph nodes after surgery to remove the prostate. Our results show that initial observation is a good option for patients with less aggressive prostate cancer features.
10.1016/j.euros.2024.06.016
Definition and Impact on Oncologic Outcomes of Persistently Elevated Prostate-specific Antigen After Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer After Radical Prostatectomy: Clinical Implications for Multimodal Therapy.
European urology oncology
BACKGROUND:The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown. OBJECTIVE:To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS:The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM. RESULTS AND LIMITATIONS:We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%. CONCLUSIONS:PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials. PATIENT SUMMARY:We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.
10.1016/j.euo.2021.06.003
Persistent Prostate-Specific Antigen After Radical Prostatectomy and Its Impact on Oncologic Outcomes.
Preisser Felix,Chun Felix K H,Pompe Raisa S,Heinze Alexander,Salomon Georg,Graefen Markus,Huland Hartwig,Tilki Derya
European urology
BACKGROUND:Persistent prostate-specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). OBJECTIVE:To investigate the impact of persistent PSA at 6wk after RP on long-term oncologic outcomes and to assess patient characteristics associated with persistent PSA. DESIGN, SETTING, AND PARTICIPANTS:Within a high-volume center database we identified patients who harbored persistent (≥0.1ng/ml) versus undetectable PSA (<0.1ng/ml) at 6wk after RP. Patients with neo- and/or adjuvant androgen-deprivation therapy (ADT) were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Logistic regression models tested for prediction of persistent PSA. Kaplan-Meier analyses and Cox regression models tested the effect of persistent PSA on metastasis-free survival (MFS), overall survival (OS), and cancer-specific survival (CSS) rates. Propensity score matching (PSM) was performed to test the impact of salvage radiotherapy (SRT) on OS and CSS in patients with persistent PSA. RESULTS AND LIMITATIONS:Of 11 604 identified patients, 8.8% (n=1025) harbored persistent PSA. At 15yr after RP, MFS, OS, and CSS were 53.0% versus 93.2% (p<0.001), 64.7% versus 81.2% (p<0.001), and 75.5% versus 96.2% (p<0.001) for persistent versus undetectable PSA, respectively. In multivariable Cox regression models, persistent PSA represented an independent predictor for metastasis (hazard ratio [HR]: 3.59, p<0.001), death (HR: 1.86, p<0.001), and cancer-specific death (HR: 3.15, p<0.001). SRT was associated with improved OS (HR: 0.37, p=0.02) and CSS (HR: 0.12, p<0.01) after 1:1 PSM. Main limitation is missing data on postoperative PSA and duration of salvage ADT. CONCLUSIONS:Persistent PSA is associated with worse oncologic outcome after RP, namely, metastasis, death, and cancer-specific death. In patients with persistent PSA, SRT resulted in improved OS and CSS. PATIENT SUMMARY:We assessed the impact of persistent prostate-specific antigen (PSA) at 6wk after radical prostatectomy on oncologic outcomes. Early persistent PSA was associated with worse metastasis-free survival, overall survival, and cancer-specific survival. Salvage radiotherapy may result in a survival benefit in well-selected patients.
10.1016/j.eururo.2019.01.048
The Significance of Prostate Specific Antigen Persistence in Prostate Cancer Risk Groups on Long-Term Oncological Outcomes.
Milonas Daimantas,Venclovas Zilvinas,Sasnauskas Gustas,Ruzgas Tomas
Cancers
OBJECTIVE:To assess the significance of prostate-specific antigen (PSA) persistence at the first measurement after radical prostatectomy (RP) on long-term outcomes in different prostate cancer risk groups. METHODS:Persistent PSA was defined as ≥0.1 ng/mL at 4-8 weeks after RP. Patients were stratified into low-, intermediate- and high-risk groups, according to the preoperative PSA, pathological stage, grade group and lymph nodes status. The ten-year cumulative incidence of biochemical recurrence (BCR), metastases, cancer-specific mortality (CSM) and overall mortality (OM) were calculated in patients with undetectable and persistent PSA in different PCa-risk groups. Multivariate regression analyses depicted the significance of PSA persistence on each study endpoint. RESULTS:Of all 1225 men, in 246 (20.1%), PSA persistence was detected. These men had an increased risk of BCR (hazard ratio (HR) 4.2, < 0.0001), metastases (HR: 2.7, = 0.002), CRM (HR: 5.5, = 0.002) and OM (HR: 1.8, = 0.01) compared to the men with undetectable PSA. The same significance of PSA persistence on each study endpoint was found in the high-risk group (HR: 2.5 to 6.2, = 0.02 to < 0.0001). In the intermediate-risk group, PSA persistence was found as a predictor of BCR (HR: 3.9, < 0.0001), while, in the low-risk group, PSA persistence was not detected as a significant predictor of outcomes after RP. CONCLUSIONS:Persistent PSA could be used as an independent predictor of worse long-term outcomes in high-risk PCa patients, while, in intermediate-risk patients, this parameter significantly predicts only biochemical recurrence and has no impact on the outcomes in low-risk PCa patients.
10.3390/cancers13102453
Identifying Patients in Whom the Follow-Up Scheme after Robot-Assisted Radical Prostatectomy Could Be Optimized in the First Year after Surgery: Reducing Healthcare Burden.
Biomedicines
BACKGROUND:The currently advised follow-up scheme of PSA testing after robot-assisted radical prostatectomy (RARP) is strict and might pose a burden to our healthcare system. We aimed to optimize the 1-year follow-up scheme for patients who undergo RARP. METHODS:All patients with histologically-proven prostate cancer (PCa) who underwent RARP between 2018 and August 2022 in the Prostate Cancer Network in the Netherlands were retrospectively evaluated. We excluded patients who underwent salvage RARP and patients who had <1 year of PSA follow-up. Postoperative PSA values were collected. Biochemical persistence (BCP) was defined as PSA level >0.10 ng/mL at 0-4 months after RARP, whereas biochemical recurrence (BCR) was defined as PSA level >0.2 ng/mL at any time point after RARP. We aimed to identify a group of patients who had a very low risk of BCR at different time points after surgery. RESULTS:Of all 1155 patients, BCP was observed in 151 (13%), of whom 79 (6.8%) had PSA ≥ 0.2 ng/mL. BCR further developed in 51 (4.7%) and 37 (3.4%) patients at 5-8 and 9-12 months after RARP, respectively. In 12 patients, BCR was found at 5-8 months after RARP in the absence of BCP. These patients represented 1.2% (12/1004) of the entire group. In other words, 98.8% (992/1004) of patients who had an unmeasurable PSA level at 0-4 months after RARP also had an unmeasurable PSA level 5-8 months after surgery. Limitations are the retrospective design and incomplete follow-up. CONCLUSIONS:Patients with an unmeasurable PSA level at 3-4 months after RARP may not need to be retested until 12 months of follow-up, as almost 100% of patients will not have the biochemically recurrent disease at 5-8 months of follow-up. This will reduce PSA testing substantially at the cost of hardly any missed patients with recurrent disease.
10.3390/biomedicines11030727
Impact of persistent PSA after salvage radical prostatectomy: a multicenter study.
Prostate cancer and prostatic diseases
BACKGROUND AND OBJECTIVE:Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes. MATERIAL AND METHODS:Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP. RESULTS:Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01). CONCLUSION:Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA.
10.1038/s41391-023-00728-5
Oncologic outcomes of patients with lymph node invasion at prostatectomy and post-prostatectomy biochemical persistence.
Urologic oncology
BACKGROUND:Pathologic nodal invasion at prostatectomy is frequently associated with persistently elevated prostate-specific antigen (PSA) and with increased risk of disease recurrence. Management strategies for these patients are poorly defined. We aimed to explore the long-term oncologic outcomes and patterns of disease progression. METHODS:We included men treated between 2000 and 2017 who had lymph node invasion at radical prostatectomy and persistently detectable prostate-specific antigen post-prostatectomy. Postoperative imaging and management strategies were collated. Patterns of recurrence and probability of metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were assessed. RESULTS:Among our cohort of 253 patients, 126 developed metastasis. Twenty-five had a positive scan within 6 months of surgery; of these, 15 (60%) had a nodal metastasis, 10 (40%) had a bone metastasis, and 4 (16%) had local recurrence. For metastasis-free survival, 5- and 10-year probabilities were 52% (95% CI 45%, 58%) and 37% (95% CI 28%, 46%), respectively. For prostate cancer-specific survival, 5- and 10-year probabilities were 89% (95% CI 84%, 93%) and 67% (95% CI 57%, 76%), respectively. A total of 221 patients proceeded to hormonal deprivation treatment alone. Ten patients received postoperative radiotherapy. CONCLUSIONS:Biochemical persistence in patients with lymph node invasion is associated with high risk of disease progression and reduced prostate cancer-specific survival. Management was hindered by the limitation of imaging modalities utilized during the study period in accurately detecting residual disease. Novel molecular imaging may improve staging and help design a therapeutic strategy adapted to patients' specific needs.
10.1016/j.urolonc.2022.10.021
Clinicopathological and oncological significance of persistent prostate-specific antigen after radical prostatectomy: A systematic review and meta-analysis.
Asian journal of urology
Objective:To investigate the association of persistently elevated prostate-specific antigen (PSA) after radical prostatectomy (RP) with clinicopathological features and long-term oncological prognosis for the development of a potential management strategy. Methods:A systematic literature search was performed using PubMed and Web of Science up to June 2021 to identify the eligible studies focusing on understanding the impact of persistent PSA in patients who underwent RP for localized prostate cancer. Meta-analyses were performed on parameters with available information. Results:A total of 32 RP studies were identified, of which 11 included 26 719 patients with consecutive cohorts and the remaining 21 comprised 24 177 patients with cohorts carrying specific restrictions. Of the 11 studies with consecutive cohorts, the incidence of persistent PSA varied between 3.1% and 34.6% with a median of 11.0%. Meta-analyses revealed patients with persistent PSA consistently showed unfavorable clinicopathological features and a more than 3.5-fold risk of poorer biochemical recurrence, metastasis, and prostate cancer-specific mortality prognosis independently, when compared to patients with undetectable PSA. Similarly, cases with persistent PSA in different specific patient cohorts with a higher risk of prostate cancer also showed a trend of worse outcomes. Conclusion:We found that the frequency of persistent PSA was about 11.0% in consecutive RP cohorts. Persistent PSA was significantly associated with unfavorable clinicopathological characteristics and worse oncological outcomes. Patients with persistent PSA after RP may benefit from early salvage treatment to delay or prevent biochemical recurrence, improving oncological outcomes for these patients. Further prospective randomized controlled trials are warranted to understand optimal systemic therapy in these patients.
10.1016/j.ajur.2022.01.002
Management of Persistently Elevated Prostate-specific Antigen After Radical Prostatectomy: A Systematic Review of the Literature.
Ploussard Guillaume,Fossati Nicola,Wiegel Thomas,D'Amico Anthony,Hofman Michael S,Gillessen Silke,Mottet Nicolas,Joniau Steven,Spratt Daniel E
European urology oncology
CONTEXT:The prognosis and optimal management of pN0/pN1 patients with persistently elevated prostate-specific antigen (PSA) 6-8 wk after radical prostatectomy (RP) remain unclear. OBJECTIVE:To perform a systematic review of oncologic outcomes and effectiveness of salvage therapies in men with a detectable PSA level after RP. EVIDENCE ACQUISITION:A systematic review was performed in May 2020. A total of 2374 articles were screened, and 25 studies including 5217 men were selected and included in the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. EVIDENCE SYNTHESIS:PSA persistence was most commonly defined as PSA >0.1 ng/ml. PSA persistence was significantly correlated with disease aggressiveness and associated with worse oncologic outcomes than in men with undetectable PSA levels. The 5-yr recurrence-free survival rates varied from 21.5% to 67.0%. The ≥10-yr cancer-specific survival was 75-88%. Salvage radiotherapy ± androgen deprivation therapy was associated with improved survival outcomes. Risk stratification according to pathologic features, PSA levels/kinetics, and genomic classifier may aid in personalization of treatment. The usefulness of molecular imaging in this setting remains underevaluated. Main limitations of this systematic review are the retrospective design of the included studies and the lack of randomized controlled trials (RCTs) focusing on this specific population. CONCLUSIONS:PSA persistence after RP is strongly correlated with poor oncologic outcomes. Our review suggests a benefit from immediate radiotherapy; however, current evidence is still low. Indication of subsequent therapies should be based on individual discussions, taking into account all the prognostic factors and the efficacy/toxicity imbalance of proposed treatment. Results from ongoing RCTs are awaited to state on the role of more intensified systemic therapy in this population. PATIENT SUMMARY:Patients with a detectable prostate-specific antigen level after surgery are at high risk of subsequent progression. Immediate radiotherapy might improve survival outcomes. Further research into the role of molecular imaging and genomic classifier is needed in this patient population.
10.1016/j.euo.2021.01.001
Prognostic Significance of Prostate-Specific Antigen Persistence after Radical Prostatectomy: A Systematic Review and Meta-Analysis.
Kimura Shoji,Urabe Fumihiko,Sasaki Hiroshi,Kimura Takahiro,Miki Kenta,Egawa Shin
Cancers
We performed a systematic review and meta-analysis to assess the prognostic value of prostate-specific antigen (PSA) persistence 4-8 weeks after radical prostatectomy (RP) in patients with prostate cancer, using studies from Medline, Scopus, and Cochrane Library, on 10 October 2020. Studies were eligible if they compared patients with postoperative PSA persistence 4-8 weeks after RP to those without such persistence to assess the value of PSA persistence in prognosticating biochemical recurrence (BCR), disease recurrence, cancer-specific mortality (CSM), and overall mortality (OM) by multivariable analysis. Our review and analysis included nine studies published between 2008 and 2019 with 14,455 patients. Of those studies, 12.0% showed postoperative PSA persistence. PSA persistence was associated with BCR (HR: 4.44, 95% CI: 2.84-6.93), disease recurrence (HR: 3.43, 95% CI: 1.62-7.25), and CSM (HR: 2.32, 95% CI: 1.83-2.95). We omitted meta-analysis on the association of PSA persistence with OM due to an insufficient number of studies. PSA persistence was associated with disease recurrence in a sub-group of patients with pathological nodal involvement (HR: 5.90, 95% CI: 3.76-9.24). Understanding detection of PSA persistence at 4-8 weeks after RP might be useful for patient counseling, follow-up scheduling, and clinical decision-making regarding adjuvant therapies.
10.3390/cancers13050948
Prognosis based on postoperative PSA levels and treatment in prostate cancer with lymph node involvement.
International journal of clinical oncology
BACKGROUND:The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies. METHODS:Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS). RESULTS:In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone. CONCLUSIONS:This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI.
10.1007/s10147-024-02580-6