Bladder Cancer-specific Survival Research Articles

Non-Muscle Invasive Bladder Cancer: Many More Patients Die With It Than Of It.

The National Cancer Institute SEER Program regularly publishes bladder-cancer specific survival statistics. However, this data is for all bladder cancers, and information for non-muscle invasive bladder cancer (NMIBC) is difficult to obtain. To quantify 5-year overall and bladder cancer-specific survival in a cohort of Department of Veterans Affairs (VA) patients diagnosed with NMIBC. We identified VA patients diagnosed with NMIBC who underwent a transurethral resection from 2003-2013. The patient demographics and Charlson Comorbidity Index were categorized. We acquired the patients' date of death from the Veterans Health Administration's Death Ascertainment File and their cause of death from the Mortality Data Repository. We calculated Kaplan Meier estimates of survival. A total of 27,008 patients were included; median age was 69 and almost all were male (99%). The median comorbidity score was 4. The most prevalent comorbidity indicators included Chronic Pulmonary Disease (48%), cancer other than Bladder (41%), and diabetes (40%). This cohort was found to have a 5-year overall survival of 68% (99% CI 67% -69%) and a 5-year bladder cancer-specific survival of 93% (99% CI 92% -94%). The 5-year bladder cancer-specific survival in patients diagnosed with non-muscle invasive bladder cancer is substantially higher than the 5-year overall survival. This difference may be related to the severity and number of comorbidities that patients in this population must manage. This warrants further research into the necessity of currently recommended high-intensity cancer surveillance for individuals with NMIBC.

Quality of life in QUILT 3.032 study: Patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) receiving IL-15RαFc superagonist N-803 plus BCG.

495 Background: Patients (pts) with BCG-unresponsive NMIBC have limited treatment options and are at an increased risk for cystectomy. Nogapendekin alfa inbakicept (NAI, also known as N-803), is an interleukin-15 superagonist (IL-15RαFc), which synergizes with BCG to elicit innate immune memory resulting in durable complete responses (CRs) in this patient population. In an open-label, 3-cohort, multicenter Phase 2/3 study of intravesical BCG plus NAI in BCG-unresponsive high-grade NMIBC (QUILT 3.032; NCT03022825), pts with carcinoma in situ (CIS; Cohort A) have a CR rate of 71% (median duration 26.6 months), 89.2% cystectomy avoidance and 100% bladder cancer specific survival at 24 months. We submit here the first quality of life (QOL) data report in the same pts cohort. Methods: Cohort A: 86 pts (median age 73 years; 87% male) with histologically confirmed BCG-unresponsive CIS with or without Ta/T1 disease, treated with intravesical BCG 50 mg plus NAI 400 μg. Mean baseline ECOG score was 0.183, with 82% of pts having score = 0. QOL was measured by the EORTC QOL Questionnaire Core 30 (QLQ-C30) and QOL NIMBC-Specific 24 Questionnaire (QLQ-NMIBC24). Results: Multivariate analyses have shown no significant changes over time for any of the measured QOL domains. Mild worsening vs. baseline in feeling ill was reported by 6% and 3% of pts by week 27 and 52, while 4% and 6% reported improvement. By week 78 and 104, 7% and 9% of pts reported improvement vs. baseline in their wellbeing with the majority being stable (non-significant). No statistically significant variations were detected in the physical function (PF) score (baseline vs. week 27, 52, 78 and 104). Higher PF scores were observed in pts responding to the therapy vs. non-responders; however, baseline value of PF was also higher in responders vs. non-responders. In contrast to historical results of BCG alone, week 27 physical function scores were numerically higher than baseline, with a subsequent nadir at week 78 and recovery to baseline by week 104 (non-significant). Hospitalizations for any reason remained low (0% - 6% per assessments) during the study. Conclusions: QOL measurement supports good tolerability of the intravesical NAI plus BCG in BCG-unresponsive, high-grade NMIBC pts with CIS. These results further strengthen the evidence of a favorable benefit: risk ratio of this novel combination immunotherapy, in a challenging disease. Clinical trial information: NCT03022825 .

Impact of Age at Diagnosis of Bladder Cancer on Survival: A Surveillance, Epidemiology, and End Results-Based Study 2004-2015.

An older age contributes to the development of bladder cancer. However, the relationship between advanced age at the diagnosis and prognosis of bladder cancer has been few reported. This study aimed to determine the effect of age on survival in bladder cancer with different subgroups. 117,275 patients with bladder cancer, identified from the Surveillance, Epidemiology, and End Results database during 2004-2015 in America, were divided into 4 age groups (≤54, 55 to 64, 65 to 74, and ≥75 years). Multivariable Cox proportional-hazards model and competing risk model were conducted according to different age groups. Heat maps were plotted to show the impact of age on survival in subgroups classified by other clinicopathological variables. Moreover, restricted cubic spline was used to model the association between age and the risk of death. Patients aged ≥75years had shorter overall survival in comparison with those aged ≤54years (hazard ratio [HR] = 5.36, 95% confidence interval [CI] = 5.13-5.59). Compared with patients aged ≤54years, patients older than 75years experienced a decreased rate of bladder cancer-specific survival (subdistribution HR = 2.15, 95% CI = 2.04-2.25). Heat maps also showed that older ages were associated with worse overall cumulative mortality and bladder cancer-specific cumulative mortality. Similarly, restricted cubic spline verified the impact of age on survival of bladder cancer. Age at diagnosis of bladder cancer was found to be a significant predictor for the worse overall survival and bladder cancer-specific survival even in an era with more effective therapies. Exploring the reasons why older age contributes to poor outcomes for bladder cancer will be the focus of future research.

IL-15 Superagonist NAI in BCG-Unresponsive Non–Muscle-Invasive Bladder Cancer

BackgroundPatients with Bacillus Calmette–Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell–activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically with BCG to elicit durable complete responses (CRs) in this patient population.MethodsIn this open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical NAI plus BCG (cohort A) or NAI alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received NAI plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival were secondary end points for cohort A.ResultsIn cohort A, CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months (95% CI=9.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan–Meier estimated probability of avoiding cystectomy and of DSS was 89.2% and 100%, respectively. In cohort B (n=72), the Kaplan–Meier estimated DFS rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]). Most treatment-emergent adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%); three grade 3 immune-related treatment-emergent adverse events occurred.ConclusionsIn patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer–specific survival at 24 months. The study is ongoing, with an estimated target enrollment of 200 participants (Funded by ImmunityBio.)

Nomogram based on baseline clinicopathological characteristics for predicting bladder cancer-specific survival to neoadjuvant chemotherapy in muscle-invasive bladder cancer.

To develop a risk score based on a prognostic model and a nomogram integrating baseline clinicopathological variables to predict bladder cancer-specific survival (BCSS) to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) patients. We retrospectively identified a consecutive sample of 247 MIBC patients treated with cisplatin-based NAC-plus-cystectomy in two Spanish hospitals between 2000 and 2019. Age at MIBC diagnosis, sex, histology, lymphovascular invasion, previous non-MIBC, hydronephrosis, and clinical TNM were included in the initial Cox regression model. A risk score was computed based on the final prognostic model and a nomogram was used to estimate BCSS at 2 and 5years. Median age was 66years; 89% were males; 83% had pure urothelial carcinoma; 16.2% had previous non-MIBC. Clinical stage was T2N0, T3-4aN0, and Tx-4N + in 24%, 57%, and 19% of patients, respectively. Complete pathological response was seen in 29.4% and downstaging to non-MIBC (ypT1, ypTa, ypTis) in 12.5% of patients. Overall 5-year BCSS was 59%. Four prognostic factors were identified: variant histology, previous non-MIBC, female sex and hydronephrosis. By adding the points attributed to each of these factors, we categorized patients in three groups: low-risk (0 points); intermediate-risk (1-9 points); high-risk (≥ 10 points). Five-year BCSS was 72%, 53%, and 15%, respectively (p < 0.0001). We developed a nomogram and risk score based on four baseline clinicopathological characteristics to predict BCSS to NAC-plus-cystectomy in MIBC patients. If validated in prospective studies, this nomogram can be useful for selecting patients likely to benefit from NAC.

AUTHOR REPLY

We thankDr. Schafer and Dr. Sundi for contributing to this timely discussion of the social and biological determinants of health disparities. As we hope to highlight, metastatic bladder cancer-specific survival has disparate outcomes between gender, race, and socioeconomic status. Given the high mortality and low overall survival of metastatic bladder cancer, this space has significant potential for improvement in care by targeting interventions for Black women and residents of high poverty areas.

Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC).

4508 Background: Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is a mutant IL-15-based immunostimulatory fusion protein complex (IL15RaFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase 1b data in BCG-naïve patients with NMIBC demonstrate that intravesical administration of N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. Pembrolizumab was approved in 2020 with a 41% complete response (CR) rate in a single arm phase 2 trial of 96 patients. We report data on 160 subjects from an open-label, 3 cohort multicenter study (QUILT 3.032) of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825). Methods: All treated patients received intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. The primary endpoint for Cohort A (CIS) is incidence of CR of CIS at any time. The primary endpoint for Cohort B (Papillary) is disease-free rate (DFS) at 12 months. Results: To date, we enrolled 160 patients (83 CIS, 77 Papillary). In the overall population, median age is 72.3 years, 81% male, with mean number of prior TURBT = 4. Median number of prior BCG doses = 12. CIS patients have a CR rate of 71% (59/83), with a mediation duration of CR of 24.1 months in responders; 91% avoided cystectomy and 96% 24 month bladder cancer specific progression free survival (defined as progression to MIBC). Papillary patients have a 57% 12 month DFS rate, 48% 24 month DFS rate, and 95% avoided cystectomy. Median time to cystectomy in responders (N = 4) is 12.9 months versus 7.8 in non-responders (N = 8) for a 5.1 month delay in cystectomy. PK data shows no systemic levels of N-803; activity is confined to the bladder. Low grade treatment related AEs (grade 1-2) include dysuria (22%), pollakiurua (19%), hematuria (18%), fatigue (16%), and urgency (12%), all other AEs were seen at 7% or less. No treatment related grade 4 or 5 AE were seen. No SAE's were considered treatment related. No immune related SAE's have been seen. Conclusions: In 160 patients with BCG-unresponsive NMIBC, there is a 99% bladder cancer specific overall survival at 2 years. In CIS patients 71% CR rate with 24.1 months median duration of response, and 53% DFS rate at 18 months in Papillary disease. Cystectomy was avoided in over 90% of patients with 2 years of follow-up. The efficacy and safety profile of N-803+BCG exceeds that of other available intravesical and systemic options for BCG-unresponsive NMIBC. Clinical trial information: NCT03022825.

Chemoradiotherapy in Muscle-invasive Bladder Cancer: 10-yr Follow-up of the Phase 3 Randomised Controlled BC2001 Trial

BackgroundBC2001, the largest randomised trial of bladder-sparing treatment for muscle-invasive bladder cancer (MIBC), demonstrated improvement in locoregional control by adding fluorouracil and mitomycin C to radiotherapy (James ND, Hussain SA, Hall E, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012;366:1477–88). There are limited data on long-term recurrence risk. ObjectiveTo determine whether benefit of adding chemotherapy to radiotherapy for MIBC is maintained in the long term. Design, setting, and participantsA phase 3 randomised controlled 2 × 2 factorial trial was conducted. Between 2001 and 2008, 458 patients with T2-T4a N0M0 MIBC were enrolled; 360 were randomised to radiotherapy (178) or chemoradiotherapy (182), and 218 were randomised to standard whole-bladder radiotherapy (108) or reduced high-dose-volume radiotherapy (111). The median follow-up time was 9.9 yr. The trial is registered (ISRCTN68324339). InterventionRadiotherapy: 55 Gy in 20 fractions over 4 wk or 64 Gy in 32 fractions over 6.5 wk; concurrent chemotherapy: 5-fluorouracil and mitomycin C. Outcome measurements and statistical analysisLocoregional control (primary endpoint), invasive locoregional control, toxicity, rate of salvage cystectomy, disease-free survival (DFS), metastasis-free survival (MFS), bladder cancer–specific survival (BCSS), and overall survival. Cox regression was used. The analysis of efficacy outcomes was by intention to treat. Results and limitationsChemoradiotherapy improved locoregional control (hazard ratio [HR] 0.61 [95% confidence interval {CI} 0.43–0.86], p = 0.004) and invasive locoregional control (HR 0.55 [95% CI 0.36–0.84], p = 0.006). This benefit translated, albeit nonsignificantly, for disease-related outcomes: DFS (HR 0.78 [95% CI 0.60–1.02], p = 0.069), MFS (HR 0.78, [95% CI 0.58–1.05], p = 0.089), overall survival (HR = 0.88 [95% CI 0.69–1.13], p = 0.3), and BCSS (HR 0.79 [95% CI 0.59–1.06], p = 0.11). The 5-yr cystectomy rate was 14% (95% CI 9–21%) with chemoradiotherapy versus 22% (95% CI 16–31%) with radiotherapy alone (HR 0.54, [95% CI 0.31–0.95], p = 0.034). No differences were seen between standard and reduced high-dose-volume radiotherapy. ConclusionsLong-term findings confirm the benefit of adding concomitant 5-fluorouracil and mitomycin C to radiotherapy for MIBC. Patient summaryWe looked at long-term outcomes of a phase 3 clinical trial testing radiotherapy with or without chemotherapy for patients with invasive bladder cancer. We concluded that the benefit of adding chemotherapy to radiotherapy was maintained over 10 yr.

PLLBA-01 FINAL CLINICAL RESULTS OF PIVOTAL TRIAL OF IL-15RΑFC SUPERAGONIST N-803 WITH BCG IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) CIS AND PAPILLARY COHORTS

You have accessJournal of UrologyCME1 May 2022PLLBA-01 FINAL CLINICAL RESULTS OF PIVOTAL TRIAL OF IL-15RΑFC SUPERAGONIST N-803 WITH BCG IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) CIS AND PAPILLARY COHORTS Sam Chang, Karim Chamie, Mark Hidalgo, Eugene Kramolowsky, Wade Sexton, Sandeep Reddy, and Patrick Soon-Shiong Sam ChangSam Chang More articles by this author , Karim ChamieKarim Chamie More articles by this author , Mark HidalgoMark Hidalgo More articles by this author , Eugene KramolowskyEugene Kramolowsky More articles by this author , Wade SextonWade Sexton More articles by this author , Sandeep ReddySandeep Reddy More articles by this author , and Patrick Soon-ShiongPatrick Soon-Shiong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002671.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is a mutant IL-15-based immunostimulatory fusion protein complex (IL15RaFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase 1b data in BCG-naïve patients with NMIBC demonstrate that intravesical N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. An open-label, 3 cohort multicenter study (QUILT 3.032) of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened. We report data on 160 subjects. METHODS: All treated patients received intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. The primary endpoint for Cohort A (CIS) is incidence of complete response (CR) of CIS at any time. The primary endpoint for Cohort B (Papillary) is disease-free rate (DFS) at 12 months. RESULTS: To date, 83 patients have enrolled in cohort A, 77 in Cohort B. In the overall population, median age is 72.3 years, 81% male, with mean number of prior TURBT=4. Median number of prior BCG doses = 12. CIS patients have a CR rate of 71% (59/83), with a mediation duration of CR of 24.1 months in responders; 91% avoided cystectomy and 96% 24 month bladder cancer specific progression free survival (defined as progression to MIBC). Papillary patients have a 57% 12 month DFS rate, 48% 24 month DFS rate, and 95% avoided cystectomy. Median time to cystectomy in responders (N=4) is 12.9 months versus 7.8 in non-responders (N=8) for a 5.1 month delay in cystectomy. PK data shows no systemic levels of N-803; thus activity is confined to the bladder. Low grade treatment related AEs (grade 1-2) include dysuria (22%), pollakiurua (19%), hematuria (18%), fatigue (16%), and urgency (12%), all other AEs were seen at 7% or less. No treatment related grade 4 or 5 AE were seen. No treatment emergent SAE's were considered treatment related. No immune related SAE's have been seen. Final data will be presented at AUA. CONCLUSIONS: In 160 patients with BCG-unresponsive NMIBC, there is a 99% bladder cancer specific overall survival at 2 years. In CIS patients 71% CR rate with 24.1 months median duration of response and 96% absence of progression to MIBC at 24 months. 53% DFS rate at 18 months in Papillary disease, N-803+BCG efficacy and safety profile exceeds other available intravesical and systemic options. Source of Funding: ImmunityBio © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1047 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sam Chang More articles by this author Karim Chamie More articles by this author Mark Hidalgo More articles by this author Eugene Kramolowsky More articles by this author Wade Sexton More articles by this author Sandeep Reddy More articles by this author Patrick Soon-Shiong More articles by this author Expand All Advertisement PDF DownloadLoading ...

Outcomes by time to definitive chemoradiation treatment for patients with muscle-invasive bladder cancer.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has raised concerns about delaying treatment for localized cancer and its impact on long-term outcomes.ObjectiveWe aimed to investigate the impact of time to chemoradiation (CRT) on recurrence and survival outcomes for patients with muscle-invasive bladder cancer (MIBC).MethodsIn the national Veterans Affairs’ database, we identified patients with urothelial histology, MIBC (T2-4a/N0-3/M0) diagnosed between 2000 to 2018 and treated with definitive CRT. Time to treatment was defined as the number of days between date of diagnosis and start date of CRT. The cohort was stratified into < 90 (early) or ≥ 90 days (delayed) groups. Endpoints of locoregional failure (LRF), distant failure (DF), overall survival (OS), and bladder cancer-specific survival (BCS) were evaluated in multivariable Cox and Fine-Gray models.Results305 patients with MIBC underwent CRT – 190 (62.3%) received early CRT, 115 (37.7%) received delayed CRT. Multivariable analysis (including success of transurethral resection of bladder tumor and type of chemotherapy) revealed no difference in recurrence between groups – LRF HR 1.12 (95%CI 0.76-1.67, P = 0.56) and DF HR 1.03 (95%CI 0.70-1.53, P = 0.88). Similarly, there were no differences in survival outcomes. The lack of association was maintained at both earlier and later time cutoffs (60–120 days).ConclusionsOur findings suggest that a short-term delay in definitive therapy may not affect long-term outcomes for patients with MIBC undergoing CRT. This study does not endorse delays in therapy, but rather provides information to aid patients and clinicians navigate the unique challenges of MIBC care in both pandemic and non-pandemic times.

The prognostic impact of preoperative health-related quality life on bladder cancer-specific survival in patients treated with radical cystectomy.

475 Background: Previous studies have shown that baseline health-related quality of life (HRQOL) is a valuable prognostic indicator of survival outcomes for various cancer entities in the metastatic setting, yet there is no evidence on the prognostic value of baseline HRQOL for patients undergoing radical cystectomy (RC) with curative intent. The goal of this study was to evaluate the influence of baseline preoperative HRQOL on cancer specific survival prognosis for patients undergoing RC. Methods: 407 patients with prospectively assessed baseline HRQOL prior RC were included. Patients were stratified by the global health status (GHS) domain of the EORTC QLQ-C30 questionnaire, and good general HRQOL was defined as GHS≥70 based on validated cut-off levels. A 1:2 propensity-score-matched analysis of n=357 patients [n=125 (GHS≥70), n=232 (GHS&lt;70)] was performed. Primary endpoint was cancer-specific survival (CSS), secondary endpoints encompassed overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox regression models were performed to assess prognostic significance of baseline GHS on survival outcomes. Harrell’s discrimination C-index was assessed to calculate the predictive accuracy of the model (p&lt;0.05). Results: Median follow-up was 40.5mo. Patients subcohorts were well-balanced. All baseline QLQ-C30 functioning scales were in favour of the GHS≥70 cohort (each p&lt;0.001). 5-yr CSS (82% vs. 65%; p=0.001), 5-yr OS (76% vs 53%; p=0.001) and 5-yr-RFS (50% vs. 39%; p=0.04) and were significantly increased in the GHS≥70 cohort. GHS≥70 was confirmed as an independent predictor for increased CSS (HR 0.43, 95%CI 0.21–0.89; p=0.028), OS (HR 0.56, 95%CI 0.31–0.90; p=0.031) and RFS (HR 0.52, 95%CI 0.31–0.87; p=0.013) multivariate analysis. Conclusions: Our findings suggest preoperative baseline HRQOL to have a pronounced predictive value for patients undergoing RC with curative intent for bladder cancer. We found baseline good general HRQOL to accurately predict increased CSS, OS and RFS.[Table: see text]

Baseline Health-related Quality of Life Predicts Bladder Cancer–specific Survival Following Radical Cystectomy

BackgroundIt has been shown that baseline health-related quality of life (HRQOL) is a valuable prognostic indicator of survival outcomes for various metastatic cancers, but there is no evidence on the prognostic value of baseline HRQOL for patients with bladder cancer undergoing radical cystectomy (RC) and ileal conduit (IC) or orthotopic ileal neobladder (ONB) with curative intent. ObjectiveTo assess the association between baseline HRQOL and survival outcomes following RC. Design, setting, and participantsThe study included 407 patients with prospectively assessed baseline HRQOL before RC. Patients were stratified according to the Global Health Status (GHS) domain of the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, with good general HRQOL defined as GHS ≥70 on the basis of validated cutoff levels. A propensity score–matched analysis of 357 patients (1:2 ratio; 125 patients with GHS ≥70 vs 232 with GHS <70) was performed. InterventionRC with IC or ONB. Outcome measures and statistical analysisThe primary endpoint was cancer-specific survival (CSS). The secondary endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier and multivariate Cox regression models were constructed to assess the prognostic value of baseline GHS for prediction of survival outcomes. Results and limitationsMedian follow-up was 40.5 mo. The rates of 5-yr CSS (82% vs 65%; p = 0.001), 5-yr OS (76% vs 53%; p = 0.001), and 5-yr RFS (50% vs 39%; p = 0.04) were significantly higher in the GHS ≥70 cohort. GHS ≥70 was confirmed as an independent predictor for CSS (hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.18–0.73; p = 0.004), OS (HR 0.45, 95% CI 0.26–0.79; p = 0.005), and RFS (HR 0.50, 95% CI 0.30–0.83; p = 0.008) in multivariate analyses. Study limitations include the retrospective analysis of prospectively collected data and use of a HRQOL questionnaire not specifically for bladder cancer. ConclusionsOur findings suggest that preoperative baseline HRQOL has significant predictive value for outcomes of RC with curative intent for bladder cancer. We found that good general HRQOL at baseline accurately predicts greater CSS, OS, and RFS. Patient summaryWe assessed the association between health-related quality of life at baseline and survival outcomes after radical cystectomy for bladder cancer. We found that good general health-related quality of life at baseline predicts better survival outcomes and that higher baseline scores were associated with greater cancer-specific survival.

Associations between body mass index and bladder cancer survival: Is the obesity paradox short-lived?

We investigated the associations of pre-surgical body mass index (BMI) with bladder cancer outcomes in patients treated with radical cystectomy. We retrospectively analyzed data from 488 bladder cancer patients treated with radical cystectomy between 1994 and 2007 and followed up until 2016. Cox regression with step function (time-segment analysis) was conducted for overall survival because the proportional hazard assumption was violated. Of 488 bladder cancer patients, 155 (31.8%) were normal weight, 186 (38.1%) were overweight, and 147 (30.1%) were obese. During the median followup of 59.5 months, 363 (74.4%) patients died, including 197 (40.4%) from bladder cancer. In adjusted Cox regression analyses, BMI was not significantly associated with bladder cancer-specific survival for overweight (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.57-1.10, p=0.16) or obese (HR 0.76, 95% CI 0.52-1.09, p=0.13) patients. In the Cox regression with step function for overall survival, the time interaction was significant overall (p=0.020) and specifically for over-weight patients (p=0.006). In the time-segment model, the HR for overweight during the first 63 months was 0.66 (95% CI 0.49-0.90, p=0.008), whereas it was 1.41 (95% CI 0.89-2.23, p=0.14) after 63 months. Although not statistically significant, a similar pattern was observed for obese patients. Our findings suggest that overweight and obese bladder cancer patients had better outcomes within the first five years after radical cystectomy; however, there were no differences in longer-term survival. These data suggest that the obesity paradox in bladder cancer patients treated with radical cystectomy may be short-lived.

Adjuvant Radiotherapy After Radical Cystectomy for Patients with High-risk Muscle-invasive Bladder Cancer: Results of a Multicentric Phase II Trial

BackgroundHigh-risk muscle-invasive bladder cancer (MIBC) has a poor prognosis. Old trials showed that external beam radiotherapy (EBRT) after radical cystectomy (RC) decreases the incidence of local recurrences but induces severe toxicity. ObjectiveTo evaluate the toxicity and local control rate after adjuvant EBRT after RC delivered with volumetric arc radiotherapy. Design, setting, and participantsThis is a multicentric phase 2 trial. From August 2014 till October 2020, we treated 72 high-risk MIBC patients with adjuvant EBRT after RC. High-risk MIBC is defined as ≥pT3-MIBC ± lymphovascular invasion, fewer than ten lymph nodes removed, pathological positive lymph nodes, or positive surgical margins. InterventionPatients received 50 Gy in 25 fractions with intensity-modulated radiotherapy to the pelvic lymph nodes ± cystectomy bed. Outcome measurements and statistical analysisThe primary outcome is acute toxicity. We report on local relapse-free rate (LRFR), clinical relapse-free survival (CRFS), overall survival (OS), and bladder cancer–specific survival (BCSS). Results and limitationsThe median follow-up is 18 mo. Forty-two patients (61%) developed acute grade 2 gastrointestinal (GI) toxicity. Four patients (6%) had acute grade 3 GI toxicity. One patient had grade 5 diarrhea and vomiting due to obstruction at 1 mo. Two-year probabilities of developing grade ≥3 and ≥2 GI toxicity were 17% and 76%, respectively. Urinary toxicity, assessed in 17 patients with a neobladder, was acceptable with acute grade 2 and 3 urinary toxicity reported in 53% (N = 9) and 18% (N = 3) of the patients, respectively. The 2-yr LRFR is 83% ± 5% and the 2-yr CRFS rate is 43% with a median CRFS time of 12 mo (95% confidence interval: 3–21 mo). Two-year OS and BCSS are 52% ± 7% and 62% ± 7%, respectively. Shortcomings are the nonrandomized study design and limited follow-up. ConclusionsAdjuvant EBRT after RC can be administered without excessive severe toxicity. Patient summaryIn this report, we looked at the incidence of toxicity and local control after adjuvant external beam radiotherapy (EBRT) following radical cystectomy (RC) in high-risk muscle-invasive bladder cancer patients. We found that adjuvant EBRT was feasible and resulted in good local control. We conclude that these data support further enrollment of patients in ongoing trials to evaluate the place of adjuvant EBRT after RC.

Diet Quality and Survival in a Population-Based Bladder Cancer Study

Nutrition may impact bladder cancer survival. We examined the association between diet quality and overall and bladder cancer-specific survival. Bladder cancer cases from a population-based study reported pre-diagnosis diet. Diet quality was assessed using the 2010 Alternate Healthy Eating Index (AHEI-2010). Vital status was ascertained from the National Death Index. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards and competing risks regression models. Overall AHEI-2010 adherence was not associated with overall or bladder cancer-specific survival among non-muscle invasive bladder cancer (NMIBC) cases (HR, 1.00; 95% CI, 0.98-1.01; HR, 1.00; 95% CI, 0.97-1.02) or muscle invasive bladder cancer (MIBC) cases (HR, 0.99; 95% CI, 0.96-1.03; HR, 1.01, 95% CI 0.97-1.06). AHEI-2010 sugar-sweetened beverages adherence was associated with poorer overall survival (HR, 1.04; 95% CI, 1.01-1.08) and AHEI-2010 sodium adherence was associated with better overall and bladder cancer-specific survival after NMIBC diagnosis (HR, 0.92, 95% CI, 0.85-1.00; HR, 0.82; 95% CI, 0.68-0.98). AHEI-2010 fruit adherence was associated with poorer overall and bladder cancer-specific survival after MIBC diagnosis (HR, 1.17; 95% CI, 1.02-1.33; HR, 1.26; 95% CI, 1.03-1.55). Consumption of sugar-sweetened beverages, sodium, and fruit, not overall AHEI-2010 adherence, may be associated with bladder cancer survival.

Risk of bladder cancer death in patients younger than 50 with non-muscle-invasive and muscle-invasive bladder cancer

Introduction and objectives Bladder cancer is primarily a disease of older age and little is known about the differences between patients diagnosed with bladder cancer at a younger versus older age. Our objectives were to compare bladder cancer specific survival in patients aged <50 versus those aged 50–70 at time of diagnosis. Materials and methods The Swedish bladder cancer database provided data on patient demographics, clinical characteristics and treatments for this observational study. Cox proportional hazard regression models were adjusted for appropriate variables. All analyses were stratified by disease stage (non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Furthermore, we compared the frequency of lower urinary tract infections within 24 months prior to bladder cancer diagnosis by sex and age groups. Results The study included 15,452 newly-diagnosed BC patients (1997–2014); 1,207 (8%) patients were <50 whilst 14,245 (92%) were aged 50–70. Patients aged <50 at diagnosis were at a decreased risk of bladder cancer death (HR = 0.82, 95%CI: 0.68–0.99) compared to those aged 50–70. When stratified by non-muscle-invasive and muscle-invasive bladder cancer, this association remained in non-muscle-invasive patients only (<50, HR = 0.43, 95% CI: 0.28–0.64). The frequency of lower urinary tract infection diagnoses did not differ between younger and older patients in either men or women. Conclusions Patients diagnosed with non-muscle-invasive bladder cancer when aged <50 are at decreased risk of bladder cancer-specific death when compared to their older (50-70) counterparts. These observations raise relevant research questions about age-related differences in diagnostic procedures, clinical decision-making and, not least, potential differences in tumour biology.

The impact of the social construct of race on outcomes among bacille Calmette-Guérin-treated patients with high-risk non-muscle-invasive bladder cancer in an equal-access setting.

The objective of this study was to describe bladder cancer outcomes as a function of race among patients with high-risk non-muscle-invasive bladder cancer (NMIBC) in an equal-access setting. A total of 412 patients with high-risk NMIBC who received bacille Calmette-Guérin (BCG) from January 1, 2010, to December 31, 2015, were assessed. The authors used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, disease-specific, and overall survival outcomes. A total of 372 patients who had complete data were included in the analysis; 48 (13%) and 324 (87%) were Black and White, respectively. There was no difference in age, sex, smoking status, or Charlson Comorbidity Index by race. White patients had a higher socioeconomic status with a greater percentage of patients living above the poverty level in comparison with Black patients (median, 85% vs 77%; P < .001). A total of 360 patients (97%) received adequate induction BCG, and 145 patients (39%) received adequate maintenance BCG therapy. There was no significant difference in rates of adequate induction or maintenance BCG therapy according to race. There was no significant difference in recurrence (hazard ratio [HR], 1.53; 95% confidence interval [CI], 0.64-3.63), progression (HR, 0.77; 95% CI, 0.33-1.82), bladder cancer-specific survival (HR, 1.01; 95% CI, 0.30-3.46), or overall survival (HR, 0.97; 95% CI, 0.56-1.66) according to Black race versus White race. In this small study from an equal-access setting, there was no difference in the receipt of BCG or any differences in bladder cancer outcomes according to race.

Impact of equal access healthcare on race disparities in bladder cancer.

399 Background: Outcomes in bladder cancer are disproportionately worse for black patients compared to white patients. We hypothesize these disparities arise in part due to differences in access to healthcare and therefore may be mitigated in an equal access healthcare system, such as the Veterans Affairs’ (VA) system. Here, we examine outcomes by race for patients with bladder cancer within the VA system and then compare these outcomes to those in the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We performed a retrospective cohort study using VA Informatics and Computing Infrastructure (VINCI) and SEER. We included all patients diagnosed with bladder cancer, American Joint Committee on Cancer (AJCC) stage 0-4 diagnosed between 2000 and 2018. Endpoints of overall survival (OS), bladder cancer-specific survival (BCS), and non-bladder cancer-specific survival (NCS) were evaluated in multivariable Cox and Fine-Gray models. Results: Using the VA dataset, we identified 36322 veterans (9.0% black, 91.0% white) with bladder cancer. Black veterans were more likely to have more comorbidities, reside in zip codes with lower median income and education levels, and present with higher stage disease (AJCC stages 2-4) than white veterans (23.3% vs 19%). In multivariable models accounting for disease stage among other covariables, there were no statistically significant differences in any survival endpoint (Table). Using the SEER dataset, we identified 130998 patients (5.9% black, 94.1% white) with bladder cancer. In similar multivariable models, SEER’s black patients had statistically significant inferior outcomes in all survival endpoints compared to SEER’s white patients (Table). Conclusions: While racial disparities for patients with bladder cancer in the SEER database were observed, no differences in survival outcomes between black and white patients were observed in the VA healthcare system. Of note, black veterans presented with more advanced stage, suggesting a delay in diagnosis or a more aggressive cancer phenotype compared to white patients. Our findings underscore the need to bridge healthcare disparities across diverse racial groups. Our study highlights the beneficial impact of an equal access healthcare system in reducing financial and social barriers to healthcare to counteract racial health disparities. Further research is required to delineate these disparities and guide appropriate screening strategies. [Table: see text]

The Use of 5-Alpha Reductase Inhibitors and Alpha-1 Blockers Does Not Improve Clinical Outcome in Male Patients Undergoing Radical Cystectomy for Bladder Cancer in Quebec, Canada.

Existing literature suggests that bladder cancer (BC) outcome may be improved when patients use 5α-reductase inhibitors and/or α1-blockers, but such a conclusion may be subject to publication bias. We evaluated whether preoperative use of 5α-reductase inhibitors or α1-blockers was associated with improved clinical outcomes in a cohort of patients with BC undergoing radical cystectomy (RC). Using provincial health administrative databases, we retrospectively identified male BC patients undergoing RC in Quebec province between 2000 and 2015, and we collected data from 2 years before RC until December 2016 or death. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, propensity score matching, and uni- and multivariable Cox proportional hazards models. Covariates included age, Charlson's comorbidity index, region of residence, year of RC, distance to hospital, hospital type, annual RC volume of each hospital and surgeon, neoadjuvant chemotherapy use, and type of bladder diversion. Of the 2822 patients included, 284 patients used 5α-reductase inhibitors and 1001 patients used α1-blockers prior to surgery. Median follow-up time was 7.7 years. Patients who used 5α-reductase inhibitors or α1-blockers were generally older, had more comorbidities, and were treated more recently in academic centers. Overall, bladder cancer-specific and recurrence-free survival did not differ significantly between those using 5α-reductase inhibitors prior to surgery and controls who never used 5α-reductase inhibitors. Adjusted hazard ratios were 1.03 (95% confidence interval [CI], 0.88-1.21) for overall survival, 1.12 (95% CI, 0.92-1.36) for bladder cancer-specific survival, and 1.19 (95% CI, 0.99-1.42) for recurrence-free survival. The aforementioned outcomes were significantly worse in patients who used α1-blockers prior to surgery compared to controls, with respective adjusted hazard ratios of 1.15 (95% CI, 1.04-1.27), 1.19 (95% CI, 1.05-1.35), and 1.18 (95% CI, 1.05-1.33). Preoperative use of 5α-reductase inhibitors and α1-blockers did not improve clinical outcome in our cohort of male patients undergoing radical cystectomy for bladder cancer.

Incidental Prostate Cancer in Radical Cystoprostatectomy Specimens is Associated with Worse Overall Survival.

The impact of incidental prostate cancer (IPC) on oncological outcomes after radical cystoprostatectomy (RCP) specimens from patients with bladder cancer (BC) remains controversial. This relationship has not been well elucidated in Asian countries, where the incidence of prostate cancer has recently shown dramatic increases. This study retrospectively compared pathological features and oncological outcomes between BC patients with and without IPC in the RCP specimens. This study included 142 men who underwent RCP for BC. Men who were previously diagnosed with prostate cancer were excluded. Each prostate gland and seminal vesicle was processed as whole mounts and 4-mm close-step sectioning was performed. A single genitourinary pathologist diagnosed IPC. The pathological features and oncological outcomes such as overall survival (OS), bladder cancer-specific survival (BCSS), and progression-free survival (PFS) were compared between patients with IPC (IPC+group, n = 45) and without IPC (IPC- group, n = 97). P values less than 0.05 considered to indicate statistical significance for patients' characteristics. Because of multi-primary endpoint, P values less than 0.0167 was considered statistical significance for oncological outcomes. We detected IPC in 45 RCP specimens (31.6%). Patients in the IPC- group were significantly younger at surgery than those in the IPC+group (P < 0.001). The pathological features of the RCP specimens did not differ significantly. In multivariable analyses, presence of IPC was significantly associated with worse OS (P = 0.005), but not with either BCSS or PFS (P = 0.038 and 0.326, respectively). In Kaplan-Meier analyses, OS tended to be longer in the IPC- group than that in the IPC+group (NR vs 65 months, P = 0.0017). Our results suggested significantly better OS in patients without IPC than that in those with IPC.