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Adjuvant chemotherapy versus observation after radical cystectomy in patients with node-positive bladder cancer.

ABSTRACT: This retrospective study compared adjuvant chemotherapy (AC) versus observation after radical cystectomy (RC) in patients with node-positive bladder cancer (pN+). Outcomes were reviewed in patients with pTanyN1-3M0 bladder cancer who underwent RC with or without AC between 1995 and 2017. Baseline characteristics between the two groups were controlled with inverse probability of treatment weighting (IPTW)-adjusted analyses. Of 281 enrolled patients, the 3-year IPTW-adjusted rates of overall survival was higher in the AC group than the RC group (46.4% vs. 33.7%, p = 0.024). AC was an independent predictor of overall survival (hazard ratio = 0.48; P < 0.0001). When patients were subdivided by lymph node density (LND), the 3-year overall survival rates were similar between the AC and RC groups in patients with LND < 9%, but higher in the AC group in patients with LND 9-25% (53.4% vs. 23.7%) and LND ≥ 25% (27.4% vs. 16.1%). The numbers needed to treat to prevent one death at 3 years were three and nine in patients with LND 9-25% and ≥25%, respectively. In conclusion, AC after RC was associated with improved overall survival in patients with node-positive bladder cancer. Patients with an intermediate nodal burden may benefit most from AC.

SUBMITTER: Pak S

PROVIDER: S-EPMC6549178 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Adjuvant chemotherapy versus observation after radical cystectomy in patients with node-positive bladder cancer.

Pak Sahyun S You Dalsan D Jeong In Gab IG Song Cheryn C Lee Jae-Lyun JL Hong Bumsik B Hong Jun Hyuk JH Kim Choung-Soo CS Ahn Hanjong H

Scientific reports 20190605 1

This retrospective study compared adjuvant chemotherapy (AC) versus observation after radical cystectomy (RC) in patients with node-positive bladder cancer (pN+). Outcomes were reviewed in patients with pTanyN1-3M0 bladder cancer who underwent RC with or without AC between 1995 and 2017. Baseline characteristics between the two groups were controlled with inverse probability of treatment weighting (IPTW)-adjusted analyses. Of 281 enrolled patients, the 3-year IPTW-adjusted rates of overall survi ...[more]

PMID: 31165753

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Project description:ImportanceDespite existing evidence of a benefit associated with cisplatin-based adjuvant chemotherapy (AC) after radical cystectomy (RC) for chemotherapy-naive patients with pT3/T4 and/or pN+ urothelial carcinoma of the bladder (UCB), to our knowledge, no studies have addressed the effectiveness of AC in those who received neoadjuvant chemotherapy (NAC) before surgery.ObjectiveTo assess the comparative effectiveness of AC vs observation for patients with pT3/T4 and/or pN+ UCB previously treated with NAC and RC.Design, setting, and participantsThis observational cohort study used the National Cancer Data Base (January 1, 2006, through December 31, 2012) to identify individuals who received NAC and RC followed by AC or observation for pT3/T4 and/or pN+ UCB.Main outcomes and measuresAfter multiple imputation was used to handle missing data, inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox proportional hazards regression analyses were performed with a 6-month conditional landmark to compare overall survival (OS) among patients who received NAC and RC followed by AC vs observation. In addition, exploratory analyses were conducted to examine the heterogeneity of the treatment effect according to age (continuous), sex (female vs male), Charlson comorbidity index (≥1 vs 0), pT/N stage (pT3/T4N0 vs pTanyN+), and surgical margin status (positive vs negative) by testing interaction terms within the IPTW-adjusted Cox proportional hazards regression model.ResultsOf the 788 patients with pT3/T4 and/or pN+ UCB (mean [SD] age, 65.3 [9.4] years; 603 [76.5%] male and 185 [23.5%] female), 184 (23.4%) received NAC and RC followed by AC and 604 (76.6%) received NAC and RC followed by observation. The 6-month conditional landmark, IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for NAC and RC followed by AC (29.9 months; interquartile range, 15.1-85.4 months) vs NAC and RC followed by observation (24.2 months; interquartile range, 12.9-58.9 months) (P = .046). The 5-year IPTW-adjusted rates of OS were 36.8% for NAC and RC followed by AC vs 24.7% for NAC and RC followed by observation. In the IPTW-adjusted Cox proportional hazards regression analysis, NAC and RC followed by AC was associated with a significant OS benefit (hazard ratio, 0.78; 95% CI, 0.61-0.99; P = .046). Interaction term analyses indicated that the OS benefit of NAC and RC followed by AC decreased significantly with age (hazard ratio, 0.97; 95% CI, 0.95-0.99; P = .02), whereas no significant interaction was observed with sex (P = .82), Charlson comorbidity index (P = .51), pT/N stage (P = .95), and surgical margin status (P = .29).Conclusions and relevanceThis study found that AC after NAC and RC may be associated with an OS benefit for patients with pT3/T4 and/or pN+ UCB. The present findings should be considered as preliminary evidence to conduct a randomized clinical trial to address this association.

Project description:Introduction and objectiveMuscle invasive bladder cancer with extravesical extension is an aggressive disease entity that requires multimodal therapy. The benefits of adjuvant chemotherapy (AC) in patients with a positive soft-tissue surgical margin (STSM), however, are relatively unknown due to exclusion of this population in randomized controlled trials of AC. We sought to define survival benefits in this patient population through our institutional bladder cancer database.MethodsRetrospective review of all patients undergoing radical cystectomy for urothelial carcinoma of the bladder from 2004-2020 with ≥pT3b disease irrespective of neoadjuvant chemotherapy (NAC) use was conducted. Progression-free survival (PFS) and overall survival (OS) estimates were obtained using the Kaplan-Meier method with log-rank test, and the Cox-proportional hazards model was used to identify predictors of improved PFS and OS. AC was defined by any chemotherapy use within 90 days of cystectomy, regardless of STSM status.Results476 patients with pT3b disease or worse were identified. Median follow-up was 12.3 months. An amount of 21% of patients were treated with AC. An amount of 24% of patients had positive STSM. Median OS for patients with positive STSM was 8.4 months [95% CI 7-11.5] and 18.3 months [95% CI 15.6-20.8] (p < 0.001) for patients with negative STSM. In the overall cohort, positive STSM (HR 1.93, 95% CI 1.45-2.57, p < 0.001), AC use (HR 0.68, 95% CI 0.51-0.90, p = 0.007), and pN1-3 disease (HR 1.47, 95% CI 1.16-1.87, p = 0.002) were independent predictors of OS when adjusted for performance status, pT-stage, and neoadjuvant chemotherapy use. In patients with positive STSM, median survival was seven months [95% CI 5.2-8.4] without AC, compared to 16.2 months [95% CI 11.5-52.5] with AC (p = 0.0038). For patients with negative STSM, median survival was 17.4 months [95% CI 14-20.1] without AC compared to 22.3 months [95% CI 17.2-36.9] with AC (p = 0.23). In patients with positive STSM, AC use was the only factor associated with an OS benefit with a HR of 0.41 (95% CI 0.21-0.78, p = 0.007). In patients with negative STSM, pT4 and pN1-3 disease were the only factors associated with worse overall survival with a HR of 1.32 (95% CI 1.00-1.74, p = 0.050) and 1.97 (95% CI 1.49-2.60, p < 0.001), respectively.ConclusionsAdministration of adjuvant chemotherapy is of particular benefit in patients with positive STSM following radical cystectomy for gross extravesical disease. Positive STSM may be a representative of "early metastatic" or micrometastatic disease.

Project description:IntroductionThe management of non-metastatic clinically advanced lymph nodal (cN2/N3) bladder cancer (Stage IIIB) could involve radical cystectomy, chemoradiation, or systemic therapy alone. However, a definitive comparison between these approaches is lacking. This study aims to compare the outcomes of patients undergoing radical cystectomy with pelvic lymph node dissection (RC-PLND), chemoradiation therapy (CRT) or systemic therapy (including immunotherapy) (ST) only in patients with stage IIIB bladder cancer.Materials and methodsA retrospective analysis of the National Cancer Database for patients with stage IIIB urothelial bladder cancer was done from 2004-2019. Patients were classified as Group A: Those who received RC-PLND with perioperative chemotherapy, Group B: Those who received CRT, and Group C: Those who received only ST alone. The primary outcome was overall survival (OS). Inverse probability weighting (IPW)-adjusted Kaplan Meier curves were utilized to compare overall survival (OS) and cox multivariate regression analysis was used to identify predictors for OS.ResultsOverall, 2,575 patients were identified. They were classified into Group A (n=1,278), Group B (n=317) and Group C (n=980). Compared to Group B, patients in Group A were younger (SMD=19.6%), had lower comorbidities (SMD=18.2%), had higher income (SMD=31.5%), had private insurance (SMD= 26.7%), were treated at academic centres (SMD=29.3%) and had higher percentage of N2 disease (SMD=31.1%). Using IPW-adjusted survival analysis, compared to Group C, the median OS was significantly higher in Group A (20.7 vs 14.2 months, p<0.001) and Group B (19.7 vs 14.2 months, p<0.001) but similar between Group A and Group B (20.9 vs 19.7 months, p=0.74). Both surgery (HR=0.72 (0.65-0.80), p<0.001) and CRT (0.70 (0.59-0.82), p<0.001) appeared to be independent predictors for OS on cox-regression analysis. The major limitations include bias due to retrospective analysis and non-assessment of cancer-specific survival.ConclusionIn stage IIIB bladder cancer with advanced lymph nodal disease, both RC and CRT offer equivalent survival benefits and are superior to systemic therapy alone.

Project description:Importance:Locoregional failure for patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity and mortality. Adjuvant radiotherapy (RT) can decrease locoregional failure but has not been studied in the chemotherapy era. Objective:To investigate if adjuvant sequential RT plus chemotherapy can improve locoregional recurrence-free survival (LRFS) compared with adjuvant chemotherapy alone. Design, Setting, and Participants:A randomized phase 3 trial was opened to compare adjuvant RT vs sequential chemotherapy plus RT after RC for LABC, but a third arm was added later as a randomized phase 2 trial to compare chemotherapy plus RT vs adjuvant chemotherapy alone, an emerging standard. The intent-to-treat phase 2 trial reported herein enrolled patients from December 2002 to July 2008. Data were analyzed from August 3, 2015, to January 6, 2016. Routine follow-up and surveillance pelvic computed tomographic (CT) scans every 6 months during the first 2 years were performed. The setting was an academic center. Patients with bladder cancer 70 years or younger having 1 or more risk factors (≥pT3b, grade 3, or positive nodes) with negative margins after radical cystectomy plus pelvic lymph node dissection were eligible. Patients had Eastern Cooperative Oncology Group performance status of 0 to 2, no evidence of distant metastases on CT scan of the abdomen and pelvis or on chest imaging, and adequate renal, hepatic, and hematologic function. Ninety-one percent (109 of 120) had ≥ pT3 disease. Interventions:Chemotherapy plus RT included 2 cycles of gemcitabine (1000 mg/m2 intravenously on days 1, 8, and 15) and cisplatin (70 mg/m2 intravenously on day 2) before and after RT to 4500 cGy in 150 cGy twice-daily fractions over 3 weeks using 3-dimensional conformal techniques. Chemotherapy alone included 4 cycles of gemcitabine and cisplatin. Main Outcome and Measure:Locoregional recurrence-free survival. Results:The chemotherapy plus RT arm accrued 75 patients, and the chemotherapy-alone arm accrued 45 patients, with a weighted randomization to speed accrual. Fifty-three percent (64 of 120) had urothelial carcinoma, and 46.7% (56 of 120) had squamous cell carcinoma or other. The arms were balanced except for age (median, 52 vs 55 years; P = .04) and tumor size (mean, 4.9 vs 5.8 cm; P < .01), both favoring chemotherapy plus RT. Two-year outcomes and overall adjusted hazard ratios (HRs) for chemotherapy plus RT vs chemotherapy alone were 96% vs 69% (HR, 0.08; 95% CI, 0.02-0.39; P < .01) for LRFS, 68% vs 56% (HR, 0.53; 95% CI, 0.27-1.06; P = .07) for disease-free survival, and 71% vs 60% (HR, 0.61; 95% CI, 0.33-1.11; P = .11) for overall survival (OS). Five patients (7%) had RT-associated late grade 3 gastrointestinal tract adverse effects in the chemotherapy plus RT arm. Conclusions and Relevance:Adjuvant chemotherapy plus RT was reasonably well tolerated and was associated with significant improvements in LRFS and marginal improvements in disease-free survival vs chemotherapy alone in LABC. The addition of adjuvant RT should be considered for LABC. This regimen warrants further study in phase 3 trials. Trial Registration:clinicaltrials.gov Identifier: NCT01734798.

Project description:BackgroundThe benefit of adjuvant chemotherapy remains controversial in muscle-invasive bladder cancer (MIBC) after radical cystectomy. The present study's primary objective was to construct a predictive tool for the reasonable application of adjuvant chemotherapy.MethodsAll of the patients analyzed in the present study were recruited from the Surveillance Epidemiology and End Results program between 2004 and 2015. Propensity score matching (PSM) was used to reduce inherent selection bias. Cox proportional hazards models were applied to identify the independent prognostic factors of overall survival (OS) and cancer-specific survival (CSS), which were further used to construct prognostic nomogram and risk stratification systems to predict survival outcomes. The prognostic nomogram's performance was assessed by concordance index (C-index), receiver-operating characteristic (ROC) and calibration curves. Decision curve analysis (DCA) was performed to evaluate the clinical net benefit of the prognostic nomogram.ResultsA total of 6,384 patients with or without adjuvant chemotherapy were included after PSM. Several independent predictors for OS and CSS were identified and further applied to establish a nomogram for 3-, 5- and 10-year, respectively. The nomogram showed favorable discriminative ability for the prediction of OS and CSS, with a C-index of 0.709 [95% confidence interval (CI): 0.699-0.719] for OS and 0.728 (95% CI: 0.718-0.738) for CSS. ROC and calibration curves showed satisfactory consistency. The DCA revealed high clinical positive net benefits of the prognostic nomogram. The different risk stratification systems showed that adjuvant chemotherapy resulted in better OS (P<0.001) and CSS (P<0.001) than without adjuvant chemotherapy for high-risk patients; while the OS (P=0.350) and CSS (P=0.260) for low-risk patients were comparable.ConclusionsWe have constructed a predictive model and different risk stratifications for selecting a population that could benefit from postoperative adjuvant chemotherapy. Adjuvant chemotherapy was found to be beneficial for high-risk patients, while low-risk patients should be carefully monitored.

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Adjuvant chemotherapy versus observation after radical cystectomy in patients with node-positive bladder cancer.

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Adjuvant chemotherapy versus observation after radical cystectomy in patients with node-positive bladder cancer.

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