Improved Survival With The Addition Of Pelvic Radiotherapy To Chemotherapy In Patients With Metastatic Urothelial Carcinoma

There is little data on the benefit of local therapy to the bladder for patients with metastatic urothelial carcinoma of the bladder (mUC). We hypothesized that high-dose pelvic radiotherapy (RT) to the bladder plus chemotherapy (CT) improves overall survival (OS) vs. CT alone. We queried the NCDB for newly diagnosed mUC cases (cT1-4 N0-3 M1) from 2004-2015. We included all patients who received CT and excluded patients who received partial, total, or radical cystectomy. The RT cohort included patients who received external beam RT ≥ 45 Gy to the bladder +/- pelvic soft tissues. To account for lead time bias, we excluded patients with <2 months of follow-up or who died within 2 months of diagnosis. Logistic regression was used to identify factors associated with receipt of RT. We performed multivariable Cox proportional hazards analyses with propensity-score matching and landmark estimation to evaluate overall survival and treatment effects. We identified 3289 patients with newly diagnosed mUC who received either CT+ RT (n = 229) or CT alone (n = 3,060). Median follow-up time was 10.9 months (range 2-150), and median OS for CT+RT was 14.5 months (95% CI, 11.9-17.2) vs. 10.5 months (95% CI, 10.7-11.4) for CT alone (P<0.0001). The use of RT was associated with advanced age, higher T-stage, and treatment at a non-academic center (P<0.05). We did not identify significant associations with the receipt of RT and comorbidity score, cN stage, or local surgery (none, excisional biopsy, other). Median RT dose was 59.4 Gy (interquartile range, 50.4 – 64.8 Gy). On our unmatched multivariable analysis (MVA), RT was independently associated with improved OS (HR, 0.70; 95% CI, 0.60-0.80; P<0.0001) after adjusting for age, sex, year of diagnosis, facility type/location, insurance status, Charlson-Deyo comorbidity index, cT/N stage, number of CT agents, and type of local surgery. Increasing age, comorbidity score, and clinical T-stage were all associated with worse OS (P<0.02). On our propensity matched analysis (229 CT+RT patients matched with 229 CT patients), we observed improved OS with CT+RT vs. CT alone (median OS 14.5 months vs. 10.9 months; P = 0.001; MVA HR 0.72, 95% CI 0.59-0.87, P = 0.001). Landmark analysis for patients living ≥6 months (median OS 17.0 months for CT+RT vs. 13.8 months for CT, P = 0.007) and ≥12 months (median OS 24.2 months for CT+RT vs 17.1 months for CT, P = 0.025) also demonstrated improved outcomes for patients treated with CT+RT. In this large contemporary retrospective analysis, patients with newly diagnosed mUC who received local RT plus CT had improved OS compared to CT alone. The magnitude of the effect persisted even with a 12-month landmark analysis which should mitigate the effect of selection bias. The findings are hypothesis-generating; a prospective trial evaluating the impact of bladder RT in mUC is warranted.