Factors Associated With Treatment Discontinuation in Patients With Muscle-Invasive Bladder Cancer Undergoing Chemoradiation.

PURPOSE/OBJECTIVE(S) Radiation treatment with concurrent chemotherapy (CRT) is a definitive treatment option for muscle-invasive bladder cancer (MIBC). Despite its effectiveness, CRT is underutilized given perceptions regarding fitness of patients for treatment and subsequent utility. Within the national Veterans Affairs' (VA) database, we investigated the factors associated with and the impact of treatment discontinuation in patients with MIBC treated with CRT. MATERIALS/METHODS In the VA database, we identified patients with urothelial histology, MIBC (T2-4a/N0-3/M0) diagnosed between 2000 and 2018 and treated with definitive intent CRT. Patients' electronic health records were chart reviewed to document if they completed definitive radiation (defined as at least 55 Gy). Preferred chemotherapy regimen was defined as containing cisplatin or combination mitomycin/5-fluorouracil. Primary endpoint of discontinued radiation was evaluated in a multivariable logistic regression. Secondary endpoints of 30/90-day mortality, overall mortality (OM), bladder cancer-specific mortality (BCM), non-bladder cancer-specific mortality (NCM), locoregional failure (LRF), and distant failure (DF) were evaluated in multivariable Cox and Fine-Gray models. RESULTS Of an identified 369 veterans with MIBC who underwent CRT, 30 (8.1%) patients did not complete definitive radiation. The most common reasons for treatment discontinuation included comorbidities/infections necessitating hospital admission (63.3%) and treatment intolerance/declining performance status (26.7%). In multivariable logistic regression, the only significant sociodemographic or clinical variables associated with radiation discontinuation were creatinine clearance (CrCl) ≤ 50 (OR 3.61, 95% CI 1.51-8.66, P < 0.01) and non-preferred chemotherapy regimen (OR 3.43, 95% CI 1.36-8.67, P = 0.01). In the discontinued radiation cohort, 30-day mortality was 33.3% and 90-day mortality was 50.0% with the majority of deaths due to non-bladder cancer-specific causes. In this cohort, no patient or tumor variables were associated with either endpoint. In the completed radiation cohort, 30-day mortality was 2.7% and 90-day mortality was 6.8%. In multivariable analysis, radiation discontinuation was significantly associated with worse OM (HR 2.50, 95% CI 1.37-4.56, P < 0.01) and worse NCM (HR 2.29, 95% CI 1.21-4.32, P = 0.01). It was not associated with inferior BCM (HR 0.56, 95% CI 0.25-1.26, P = 0.16), LRF (HR 0.93, 95% CI 0.44-1.97, P = 0.85), or DF (HR 0.60, 95% CI 0.28-1.28, P = 0.19). CONCLUSION More than 90% of patients with MIBC who undergo definitive intent CRT are able to complete their radiation course. Decreased creatinine clearance and receipt of non-preferred chemotherapy notably increased the odds of not completing radiation. Further research is required to develop evidence-based guidelines on patient selection to ensure curative therapy is offered to appropriate patients.