Severe Genitourinary Events Following Definitive Radiation Therapy for Patients with Locally Advanced and Metastatic Bladder Cancer: A Single Institution Experience

Purpose/Objective(s) Trimodality therapy with radiation therapy (RT) is considered among standard of care for muscle-invasive bladder cancer, though its role in patients with locally advanced and metastatic urothelial carcinoma (LA-UC, M-UC) is less well understood. Local RT for metastatic prostate cancer has shown reduction in the incidence of severe genitourinary (GU) events. We therefore aim to evaluate the impact of RT on the rate of severe GU events in LA-UC and M-UC. Materials/Methods Patients with LA-UC, node positive, and/or M-UC receiving definitive RT with a dose threshold of 54 Gy at a single institution from June 2017 to January 2023 were assessed for severe GU events (nephrostomy, ureteral stents, catheterization, cystoscopic and/or surgical intervention) following RT. Kaplan-Meier analysis was used to estimate time-to-event outcomes. Results There were 20 patients treated with definitive RT following transurethral resection of bladder tumor. Most were men (65%) with a median age of 70.5 years. Patients had locally advanced T3-4 (80%), node positive (45%), and/or metastatic disease (30%), mostly with pure urothelial carcinoma (60%) or variant squamous cell (25%) histology. Hydronephrosis was present at diagnosis in 11 patients (27% resolved post RT; 9% PCN removed). The majority of patients were treated with concurrent systemic therapy (85%), most commonly with pembrolizumab (53%), while 15% of patients received RT alone. Induction chemotherapy therapy was delivered in 65% of patients (37% platinum-based). The predominant radiation technique used was intensity modulated RT (90%), while 10% of patient received 3D conformal RT. The median dose was 59.4 Gy (range = 50-65 Gy) with either conventional (70%) or hypofractionated (30%) regimens to the bladder (95%) or pelvis (5%), and 60% of patients received nodal RT. The median follow-up from completion of RT was 17.1 months (range = 3.9-74.9 months). There were severe GU events in 7 patient (35%) of patients with a mean time to event of 10.5 months (range = 0.4-74.9 months). Interestingly, patients who were 75 years old were significantly less likely to have a severe GU event than patients <75 years old (11% vs 54%, p = 0.029). There were no differences in severe GU events for patients stratified by RT dose/fractionation, presence of hydronephrosis, urothelial vs variant histology, use of concurrent chemotherapy, nodal RT, or M0 vs M1 disease. Conclusion Our findings suggest that RT for LA-UC and M-UC may extend time to severe GU events, particularly in elderly patients. This could potentially reduce disruptions in systemic therapy, enhance quality of life, and decrease hospitalizations. As this study is limited by sample size and potential selection bias, further validation and comparison studies are warranted to confirm these observations and guide clinical decision-making.