Outcomes for Muscle-invasive Bladder Cancer with Radical Cystectomy or Trimodal Therapy in US Veterans

Abstract

Background Muscle-invasive bladder cancer (MIBC) remains undertreated despite multiple potentially curative options. Both radical cystectomy (RC) with or without neoadjuvant chemotherapy and trimodal therapy (TMT), including transurethral resection of bladder tumor followed by chemoradiotherapy, are standard treatments. Objective To evaluate real-world clinical outcomes of RC with neoadjuvant chemotherapy (RC-NAC), RC without NAC, TMT with National Comprehensive Cancer Network guideline–preferred radiosensitizing chemotherapy including cisplatin or mitomycin-C and 5-fluorouracil (pTMT), and TMT with nonpreferred chemotherapy (npTMT). Design, setting, and participants US veterans with nonmetastatic MIBC (T2-4aN0-3M0) were studied. Outcome measurements and statistical analysis Overall mortality (OM) was evaluated with multivariable Cox proportional hazard model. Bladder cancer-specific mortality (BCSM) was evaluated with multivariable Fine-Gray regression. Salvage cystectomy rates were obtained by chart review. Results and limitations Overall 2306 patients were included: 1472 (64%) with RC without NAC, 506 (22%) with RC-NAC, 163 (7%) with pTMT, and 165 (7%) with npTMT. On multivariable analysis, pTMT was associated with similar OM (hazard ratio [HR] 1.19; 95% confidence interval [CI] 0.94–1.50; p = 0.15) and BCSM (HR 1.34; 95% CI 0.99–1.83; p = 0.06) to RC-NAC; npTMT was associated with worse OM (HR 1.30; 95% CI 1.04–1.61; p = 0.02) and BCSM (HR 1.45; 95% CI 1.09–1.94; p = 0.01). RC without NAC was associated with similar OM (HR 1.08; 95% CI 0.95–1.24; p = 0.24) and BCSM (HR 1.02; 95% CI 0.86–1.21; p = 0.79). When stratified by age, among patients ≥65 yr of age, treatment with pTMT was associated with similar OM (HR 1.14; 95% CI 0.87–1.50; p = 0.35) and BCSM (HR 1.11; 95% CI 0.76–1.62; p = 0.60). Among patients <65 yr of age, pTMT was associated with worse OM (HR 1.82; 95% CI 1.14–2.91; p = 0.01) and BCSM (HR 2.51; 95% CI 1.52–4.13; p < 0.01). The 5-yr cumulative incidence of salvage cystectomy in the TMT group was 3.6%. Conclusions In MIBC, patients receiving pTMT have comparable survival in RC-NAC patients ≥65 yr and inferior survival in RC-NAC patients <65 yr. Salvage cystectomy rates were low. Patient summary Management of muscle-invasive bladder cancer is a multidisciplinary effort requiring thoughtful discussions with patients about treatment options, including trimodal therapy, which is an effective treatment option.

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

“…However, given that the rate of locoregional failure in this cohort appears similar to respective rates within prospective cohorts [15] , [16] , we postulate a similar pattern of more non-muscle-invasive recurrences than muscle-invasive recurrences within this cohort. In conjunction with additional retrospective studies demonstrating similar outcomes between MIBC treated with RC and MIBC treated with CRT in appropriately selected individuals [17] , [18] , CRT appears to be an efficacious option for many patients with MIBC. However, during the COVID-19 pandemic, attention has been brought to the impact of delay in oncologic treatment as hospital systems react to the fluctuations in COVID-19 burden to minimize risk of spread and mitigate risk of COVID-19 disease complications in at risk-individuals [1] , [2] .…”

Current State of Cell Therapies for Genitourinary Malignancies

“…Bladder cancer is the fourth most common cancer in men, with most patients presenting with non–muscle-invasive bladder cancer 47–49 . Despite early intervention with intravesical therapies, many patients develop recurrent disease or progress to muscle-invasive bladder cancer, where the primary treatment is radical cystectomy or trimodal therapy 50,51 . Half of patients who undergo radical cystectomy will recur within 2 years, and a portion will develop distal metastases 52,53 .…”

“…[47][48][49] Despite early intervention with intravesical therapies, many patients develop recurrent disease or progress to muscleinvasive bladder cancer, where the primary treatment is radical cystectomy or trimodal therapy. 50,51 Half of patients who undergo radical cystectomy will recur within 2 years, and a portion will develop distal metastases. 52,53 This high rate of disease recurrence and lack of therapeutic durability in multiple stages of treatment highlight a gap in bladder cancer disease management.…”

The role of surgery for locally advanced urothelial cancers

“…A study by Schuettfort et al reported a disease-free survival of 54.3 and 45.6% at 5 and 10 years after salvage radical cystectomy [15]. However, given the previously radiated field, concern for higher rates of postoperative complications has hampered its wide-spread utilization with approximately 3.6–20% of patients requiring salvage radical cystectomy after trimodal therapy [15,16]. Pieretti et al reported that salvage radical cystectomy was associated with higher rates of late complications or those occurring greater than 90 days postoperatively such as small bowel obstruction in 15%, stomal stenosis in 5%, and distal ureteral stricture in 15% compared with primary cystectomy where they reported rates of 2.4, 1.9, and 3.8%, respectively.…”