Adjuvant Radiotherapy After Radical Cystectomy for Muscle-invasive Bladder Cancer: A Phase 2 Trial-Results of Secondary Endpoints.

Background and objective: Patients with muscle-invasive bladder cancer (MIBC) who develop a recurrence after radical cystectomy (RC) have poor outcomes. This study aims to evaluate the safety and efficacy of adjuvant radiotherapy (ART) in mitigating pelvic recurrences in high-risk MIBC patients. We report on survival outcomes, health-related quality of life (HRQoL), and hematological toxicity for these patients.

Methods: A multicentric phase 2 trial was conducted from August 2014 to October 2020, in which 72 high-risk MIBC patients received ART after RC. High risk was defined by the presence of one or more of the following criteria: pT3 stage and lymphovascular invasion, pT4 stage, fewer than ten lymph nodes removed, positive lymph nodes, and positive surgical margins. Using intensity-modulated radiotherapy, patients with pelvic lymph nodes ± cystectomy bed (in case of a positive surgical margin) received 50 Gy in 25 fractions. Outcomes were local relapse-free rate (LRFR), clinical relapse-free survival (CRFS), overall survival (OS) (Kaplan-Meier statistics), HRQoL (European Organisation for Research and Treatment of Cancer QLQ-C30/QLQ-BLM30 surveys), and hematological toxicity (Common Terminology Criteria for Adverse Events grading).

Key findings and limitations: The median follow-up of patients without a recurrence was 39 mo. At 2 and 5 yr, LRFRs were 81% (95% confidence interval [CI] 71-91%) and 79% (95% CI 68-89%), CRFS rates were 32% (95% CI 21-42%) and 20% (95% CI 11-30%), and OS rates were 48% (95% CI 36-59%) and 34% (95% CI 22-45%), respectively. At the end of ART, several symptoms worsened, most returning to baseline within the first few months. Diarrhea showed the greatest deterioration, recovering to baseline score only partially. Hematological toxicity of incidence grade ≥2 included lymphopenia (75%), neutropenia (2%), thrombopenia (2%), and anemia (17%). Limitations include the single-arm design and the limited availability of blood samples and surveys.

Conclusions and clinical implications: ART after RC is well tolerated and leads to a favorable local control rate, supporting its use in clinical practice.