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Trends in neoadjuvant chemotherapy use and oncological outcomes for muscle-invasive bladder cancer in Japan: a multicenter study.

ABSTRACT: Despite benefits of neoadjuvant chemotherapy (NAC), the adoption of guideline recommendations for NAC use in patients with muscle-invasive bladder cancer (MIBC) has been slow. We aimed to evaluate temporal trends in NAC use and oncological outcomes in a representative cohort of patients with MIBC.We included 532 patients from 4 hospitals who underwent radical cystectomy (RC) for ? cT2 MIBC in 1996-2017. We retrospectively evaluated temporal changes in NAC use and progression-free and overall survival. Candidates for NAC were administered with either cisplatin- or carboplatin-based regimens. The impact of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models.Of 532 patients, 336 underwent NAC followed by RC (NAC group) and 196 underwent RC alone (Ctrl group). NAC use significantly increased from 10% (1996-2004) to 83% (2005-2016). The number of patients administered with cisplatin- and carboplatin-based regimens was 43 and 280, respectively. Oncological outcomes in the NAC group were significantly improved compared to those in the Ctrl group. Multivariable analysis with IPTW models revealed that NAC significantly improved oncological outcomes in patients with MIBC. A nomogram for 5-year overall survival predicted 16% improvement in patients undergoing NAC.NAC use for MIBC increased after 2005. Platinum-based NAC for MIBC potentially improves oncological outcomes.

SUBMITTER: Anan G

PROVIDER: S-EPMC5689672 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Trends in neoadjuvant chemotherapy use and oncological outcomes for muscle-invasive bladder cancer in Japan: a multicenter study.

Anan Go G Hatakeyama Shingo S Fujita Naoki N Iwamura Hiromichi H Tanaka Toshikazu T Yamamoto Hayato H Tobisawa Yuki Y Yoneyama Tohru T Yoneyama Takahiro T Hashimoto Yasuhiro Y Koie Takuya T Ito Hiroyuki H Yoshikawa Kazuaki K Kawaguchi Toshiaki T Sato Makoto M Ohyama Chikara C

Oncotarget 20170918 49

<h4>Objective</h4>Despite benefits of neoadjuvant chemotherapy (NAC), the adoption of guideline recommendations for NAC use in patients with muscle-invasive bladder cancer (MIBC) has been slow. We aimed to evaluate temporal trends in NAC use and oncological outcomes in a representative cohort of patients with MIBC.<h4>Methods</h4>We included 532 patients from 4 hospitals who underwent radical cystectomy (RC) for ≥ cT2 MIBC in 1996-2017. We retrospectively evaluated temporal changes in NAC use an ...[more]

PMID: 29156782

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Project description:ObjectivesTo investigate neoadjuvant chemotherapy (NAC) eligibility, utilization, and survival outcomes for muscle-invasive bladder cancer patients undergoing radical cystectomy (RC) in a Finnish population.Materials and methodsData from the Finnish National Cystectomy Database (2005-2017) was combined with Finnish Cancer Registry survival data. NAC utilization rates were reported, and downstaging rates were calculated based on final pathological staging. Logistic regression analyzed NAC usage and complete response (CR) predictors.ResultsSince 2011, 29% of 1157 patients received NAC. Its usage remained consistent, and the number of eligible patients not receiving NAC decreased during the study period. Among NAC patients, pathology T-category was pT0 (34%), pT1-Ta-Tis (16%), pT2 (23%), pT3 (20%), and pT4 (7%) tumors, with pN0 in 82%. In the RC + NAC group, the 5-year overall survival (OS) rates were 89% for patients with no residual disease (pT0N0), 82% for those with organ-confined residual disease (pT1, Tis, Ta, T2/N0), and 49% for patients with non-organ-confined residual disease (pT3+/N+). The corresponding cancer-specific survival (CSS) rates were 93%, 86%, and 57%, respectively. Patients with organ-confined residual disease after NAC had survival outcomes comparable to those who underwent RC alone. Higher age; odds ratio (OR) 0.93, [95% Confidence Interval (CI): 0.90-0.95] and Charlson Co-morbidity Index-score [OR 0.88 (0.79-0.98)] reduced the likelihood of receiving NAC, while a smaller center size increased the probability [OR 1.82 (1.02-3.28)]. More treatment cycles [OR 0.70, (95% CI: 0.51-0.93)] and a favorable GFR [OR 0.38 (0.16-0.88)] were associated with achieving CR.ConclusionWe report that NAC is well-utilized across Finland, with CR rates comparable to recent trials. Additionally, our survival rates are reasonable, and even with organ-confined residual disease after NAC, survival outcomes are similar to those who underwent RC alone.

Project description:BackgroundPartial cystectomy (PC) offers potential benefits for select patients with muscle-invasive bladder cancer (MIBC). However, the oncologic efficacy of PC may be compromised due to the underutilization of standard-of-care modalities, such as neoadjuvant chemotherapy (NAC) and pelvic lymph node dissection (PLND). We aimed to assess factors influencing the incorporation of NAC and PLND with PC and evaluate their impact on overall survival (OS).MethodsWe identified 2,832 patients with cT2-4N0M0 bladder cancer (BCa) who underwent PC between 2004 and 2019 using the National Cancer Database (NCDB). The primary endpoint was OS. Kaplan-Meier analysis compared OS in treatment modalities in PC patients. Multivariate Cox Proportional Hazards (CPH) model assessed the impact of age, sex, race, insurance, income, Charlson-Deyo Index (CDI), clinical T-stage, facility type, histology, surgical margins, NAC, PLND adequacy [≥10 lymph node (LN) yield], and adjuvant radiation treatment on OS. Multivariate logistic regressions were performed to examine predictors of NAC and PLND receipt in PC patients.ResultsTwo hundred and thirty-one patients received multi-agent NAC with PC. NAC treatment with PLND was associated with significantly improved OS (P<0.001). Median OS was 43.9 months in patients treated with PC alone, while median OS was not reached in PC patients treated with NAC & PLND. Furthermore, patients who received NAC without any PLND had a median OS of 50.6 months, while those treated with PLND without NAC had a median OS of 76.5 months. This persisted in the adjusted CPH model, where private insurance, NAC, and PLND significantly improved OS, especially when PLND yielded ≥10 LN. Conversely, age >80 years old, CDI >2, cT3-4, positive margins, and adjuvant radiation all increased adjusted mortality risk. After controlling for clinicopathologic variables, females were less likely to receive PLND [odds ratio (OR) 0.719, P=0.005], while NAC was more likely administered to PC patients diagnosed from 2016-2019 (OR 5.295, P<0.001). PC patients who received NAC were more likely to have PLND performed as part of their treatment regimen (OR 2.189, P<0.001). Additionally, patients treated at academic centers were more likely to have NAC administered and PLND performed (OR 1.745, P=0.003; OR 2.465, P<0.001, respectively).ConclusionsDespite guideline recommendations, the utilization of NAC and PLND with PC remains insufficient. Our analysis underscores the significant OS benefit of these recommended treatments as part of MIBC care. Importantly, we highlight a gradual increase in NAC and PLND receipt in recent years, centered largely at academic facilities. Notably, gender disparities exist in PLND receipt, emphasizing the need for further investigation.

Project description:BackgroundBladder-sparing chemoradiation therapy is a definitive first-line treatment option for muscle-invasive bladder cancer. Randomized trials have demonstrated that the addition of neoadjuvant chemotherapy to radical cystectomy or radiation monotherapy results in a survival benefit. Whether neoadjuvant chemotherapy improves outcomes when used with definitive chemoradiation is unknown.Patients and methodsWe identified 2566 patients in the National Cancer Data Base with cT2-4N0M0 urothelial cell carcinoma of the bladder treated with definitive intent concurrent chemoradiation from 2004 to 2015. The exposure of interest was receipt of neoadjuvant chemotherapy versus those without neoadjuvant chemotherapy. The primary outcome was overall survival defined from the time of diagnosis. Kaplan-Meier and multivariable Cox proportional hazard analyses were used to compare survival between groups. Sensitivity analyses tested (1) an interaction term for clinical T stage and (2) defining survival from start of radiation (as opposed to time of diagnosis) to address potential leading time bias.ResultsWe identified 462 patients treated with neoadjuvant chemotherapy followed by chemoradiation and 2104 patients treated with chemoradiation alone. With a median follow-up of 6.2 years, we found no difference in survival between groups: 5-year or 10-year overall survival of 30.6% (95% confidence interval [CI], 28.4%-32.9%) in the neoadjuvant group versus 31.8% (95% CI, 27.0%-36.8%) in the standard chemoradiation therapy group and 13.3% (95% CI, 11.2%-15.5%) in the neoadjuvant group versus 13.0% (95% CI, 8.4%-18.7%) in the standard chemoradiation therapy group, respectively (log-rank P = .19). On multivariable analysis we found no association between receipt of neoadjuvant chemotherapy and overall survival (hazard ratio, 1.01; 95% CI, 0.88-1.15; P = .921). The sensitivity analyses did not identify any differential effect by clinical T stage nor by defining survival from start of radiation.ConclusionThese results do not support the routine addition of neoadjuvant chemotherapy to definitive chemoradiation for bladder cancer, and optimizing the chemotherapy sequencing and regimens for bladder-preserving approaches to muscle invasive bladder cancer should continue to be studied under prospective clinical trials.

Project description:BackgroundThe COXEN gene expression model was evaluated for prediction of response to neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC).ObjectiveTo conduct a secondary analysis of the association of each COXEN score with event-free survival (EFS) and overall survival (OS) and by treatment arm.Design, setting, and participantsThis was a randomized phase 2 trial of neoadjuvant gemcitabine-cisplatin (GC) or dose-dense methotrexate-vinblastine-adriamycin-cisplatin (ddMVAC) in MIBC.InterventionPatients were randomized to ddMVAC (every 14 d) or GC (every 21 d), both for four cycles.Outcome measurements and statistical analysisEFS events were defined as progression or death before scheduled surgery, a decision to not undergo surgery, recurrence, or death due to any cause after surgery. Cox regression was used to evaluate the COXEN score or treatment arm association with EFS and OS.Results and limitationsA total of 167 evaluable patients were included in the COXEN analysis. The COXEN scores were not significantly prognostic for OS or EFS in the respective arms, but the GC COXEN score had a hazard ratio (HR) of 0.45 (95% confidence interval [CI] 0.20-0.99; p = 0.047) when the arms were pooled. In the intent-to-treat analysis (n = 227), there was no significant difference between ddMVAC and GC for OS (HR 0.87, 95% CI 0.54-1.40; p = 0.57) or EFS (HR 0.86, 95% CI 0.59-1.26; p = 0.45). Among the 192 patients who underwent surgery, pathologic response (pT0 vs downstaging vs no response) was strongly correlated with superior postsurgical survival (5-yr OS 90%, 89% and 52%, respectively).ConclusionsThe COXEN GC score has prognostic value for patients receiving cisplatin-based neoadjuvant treatment. The randomized, prospective design provides estimates of OS and EFS for GC and ddMVAC in this population. Pathologic response (<pT2) performed well as an intermediate endpoint in this modern cohort. For expediency in evaluating new regimens, pathologic response should continue to be used in phase 2 trials.Patient summaryIn this study, we evaluated a biomarker to predict the response to chemotherapy. The results did not meet the preset study parameters, but our study provides information on clinical outcomes with the use of chemotherapy before surgery for bladder cancer.

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Trends in neoadjuvant chemotherapy use and oncological outcomes for muscle-invasive bladder cancer in Japan: a multicenter study.

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Trends in neoadjuvant chemotherapy use and oncological outcomes for muscle-invasive bladder cancer in Japan: a multicenter study.

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