Organ Preservation With Definitive Radiotherapy For Elderly Patients With Muscle-Invasive Bladder Carcinoma

To evaluate the efficacy of bladder-preserving, definitive radiotherapy (RT) +/- chemotherapy (CHT) in elderly patients with muscle-invasive bladder cancer (MIBC). A retrospective study was conducted for elderly patients (≥70 yrs) with MIBC who underwent definitive RT +/- CHT between 2000 and 2016. Progression-free survival (PFS) and overall survival (OS) were estimated using the cumulative incidence function and Kaplan-Meier method, respectively. Univariable analyses were performed to identify variables associated with PFS and OS, using the Cox proportional hazards model. Patterns of recurrence and toxicity were examined. A total of 84 patients underwent definitive RT +/- CHT. Of these patients, 29% were deemed to be medically fit to undergo radical cystectomy (RC), but chose bladder-preservation. Stage II, III and IV (AJCC 7th Edition) disease was present in 61%, 29% and 11% of patients, respectively. Median age of diagnosis was 80.8 yrs[range 70.1, 94.3], and 79% were male. Maximal TURBT was performed in 86% of patients prior to RT. RT was directed to the bladder and regional pelvic lymph nodes in 69% of patients and to the bladder only in 31%. IMRT was used in 69% of treated patients, with the remainder receiving 3D-conformal. The median dose to the bladder tumor was 6490 cGy, and the median dose to the pelvic lymph nodes was 4500 cGy. Concurrent CHT was given to 71% of patients, with the majority receiving platinum-based regimens. Median follow-up was 68 months. PFS at 3 and 5 yrs was 56% and 51%, respectively. Bladder relapse occurred in 23 patients, with pelvic lymph node and distant recurrences in 7 and 26 patients, respectively. Of the 23 bladder recurrences, 11 were biopsy-proven MIBC, 6 were superficial or in situ disease and the remaining were not biopsied, as they were in the setting of distant metastases or opted for palliative care. Local control at 1, 3, and 5 yrs was 83%, 72% and 71%, respectively. Maximum TURBT was significantly associated with improved local control (HR 0.34 [95% CI, 0.13-0.85], p=0.02), whereas concurrent CHT had no impact (HR 1.33 [95% CI, 0.48-3.59], p=0.58). Freedom from pelvic nodal relapse at 3 and 5 yrs was 92% and 91%, respectively. RT covering the regional pelvic lymph nodes was not associated with pelvic recurrence (HR 0.32 [95% CI, 0.07-1.41], p=0.13). Freedom from distant failure at 3 and 5 yrs was 74% and 67%, respectively. Acute grade ≥2 urinary (GU) and gastrointestinal (GI) toxicity was seen in 38% and 26% of patients, respectively. Incidence of late grade ≥2 GU and GI toxicity was 33% and 5%, respectively. No patients died from treatment-related causes. Median OS was 23 months. OS at 3 and 5 yrs was 42% and 25%, respectively. OS was significantly better in patients that were medically fit to undergo RC (HR 0.47 [95% CI, 0.27-0.80], p<0.01) and those receiving concurrent CHT (HR 0.49 [95% CI, 0.29-0.86], p=0.01). Definitive RT +/- CHT is a safe, effective, and well-tolerated treatment strategy for elderly patients with MIBC.