Impact of Adjuvant Radiotherapy on Survival of Patients with Pathological High-Risk Muscle Invasive Bladder Cancer: A Propensity Scored Match Paired Analysis

Abstract

Radical cystectomy (RC) and pelvic lymph-node dissection (LND) is standard treatment for non-metastatic muscle-invasive urothelial bladder cancer (MIBC). However, loco-regional recurrence (LRR) is a common early event associated with poor prognosis. We tested the hypothesis that the impact of adjuvant radiotherapy (aRT) on oncological outcomes in these individuals is related to tumor characteristics. We retrospectively evaluated 490 patients with muscle invasive bladder cancer (MIBC) with a pT3-4 and/or N+ and/or positive surgical margins (PSM) disease treated with RC with or without aRT between 2000 and 2013 at five tertiary care centers. A 1:1 propensity score matched cohort was built to adjust for age, gender, and neoadjuvant chemotherapy. Multivariable Cox regression analyses on the matched cohort tested the relationship between aRT and LRR, cancer specific mortality (CSM) and overall mortality (OM). 5 years-recurrence-free survival risk stratification-tree analysis was built on the whole matched cohort. Acute Gastro-Intestinal (GI), Genito-Urinary and Blood Count Disorders (BCD) toxicities were recorded according to CTCAE V4.0 scale. Median follow-up was 25 months (Interquartile range: 11-55). Overall, 16% of patients received aRT. At multivariable analysis, aRT was associated with more favorable RR rate (hazard ratio [HR] 0.49, 95% Confidence Interval [CI]: 0.24-0.99), p=0.04). When patients were stratified into risk groups, only those with PSM benefited from aRT. These results were confirmed when 5-years recurrence-free survival was examined as an end point. Moreover, 5 % and 4 % of patients presented grade > 2 acute GI or GU toxicities, respectively. Because of poor prognosis, an effective post-operative standard of care is needed for pathological high-risk MIBC. aRT seems feasible and may have oncological benefits. Prospective trials evaluating this approach with current RT techniques should be undertaken.