Caroline Oska, Keyur J Mehta, Charles B Simone, Kristin Hsieh, Madhur K Garg, Justin Tang, Arpit M Chhabra, J Isabelle Choi, John H Chang, Arpi D Thukral, Michael Durci, Elizabeth M Nichols, Ryan Grover, James Gray, Irini Yacoub
In the largest prospective cohort of MIBC patients treated with proton therapy reported to date, protons appear to be an effective and well-tolerated radiation modality for those undergoing TMT. This is increasingly important in the present landscape of expanding systemic therapies.
BACKGROUND: Muscle-invasive bladder cancer (MIBC) is treated with radical cystectomy or trimodality therapy (TMT), which yield comparable survival outcomes. Many patients undergoing TMT experience significant toxicity related to chemoradiation. The unique physics of proton radiation may allow for a more tolerable regimen. We herein report on the safety and efficacy of proton therapy for patients with MIBC.
METHODS: Patients with non-metastatic MIBC treated with curative-intent proton radiation were enrolled in the multi-center Proton Collaborative Group (PCG) prospective, observational registry trial. Metastatic or palliatively treated patients were excluded. Baseline characteristics, including patient sex, age, stage, smoking history, and performance status, as well as details of the proton therapy, were documented. The primary endpoints were acute and late adverse events. Locoregional recurrence and overall survival were assessed.
RESULTS: Between August 2010 and April 2025, 39 adult patients were eligible for analysis. The median age was 78 years (IQR 75-85), and most patients were White (36/39, 92.3%) and male (29/39, 74.4%). Most patients were clinical stage II (23/39, 59.0%). All patients received definitive proton therapy to a median (IQR) dose of 56.8 Gy (55.0-64.8), and 66.6% received concurrent chemotherapy. With a median follow-up of 11 months, there were three local recurrences and 14 deaths, yielding a crude 92.3% local control rate and 64.1% overall survival. The 12- and 24-month actuarial overall survivals using a Kaplan-Meier analysis were 59.0% and 32.7%, respectively. The highest grade of acute genitourinary or gastrointestinal toxicity was grade 3, affecting only 2 (5.1%) and 1 (2.6%) patients, respectively. No late grade 3 or higher toxicities were reported.
CONCLUSION: In the largest prospective cohort of MIBC patients treated with proton therapy reported to date, protons appear to be an effective and well-tolerated radiation modality for those undergoing TMT. This is increasingly important in the present landscape of expanding systemic therapies.