Dose-Escalated Radiation Therapy for Muscle-Invasive Bladder Cancer: A Retrospective Analysis

Patients managed with trimodal therapy (TMT) for muscle-invasive bladder cancer remain at risk of intravesical recurrences. This retrospective analysis evaluates the efficacy and safety of dose escalation compared with standard-dose radiation therapy, with differentiation between invasive and noninvasive local control.

A multicenter retrospective analysis was conducted on patients with muscle-invasive bladder cancer who underwent TMT with contemporary radiation therapy techniques from 2015 to 2025. Patients in the standard-dose cohort received either 55 Gy in 20 fractions or 64 Gy in 32 fractions. In the dose-escalation cohort, a simultaneous integrated boost approach was undertaken to deliver up to 60 Gy in 20 fractions or 70 Gy in 32 fractions to the primary lesion. The effect of dose escalation compared with standard dose on 2-year local control for invasive and noninvasive disease, metastasis-free survival, overall survival, bladder preservation, and toxicity was investigated.

The cohort consisted of 107 patients with a median follow-up of 23 months. Dose escalation was significantly associated with improved local control of invasive disease (subdistribution hazard ratio 0.20 [0.05, 0.89], P = .035) compared with standard dosing, after adjusting for T stage. There were no differences in local control for noninvasive disease (P = .8), metastasis-free survival (P = .8), and overall survival (P = .5). Both groups tolerated radiation therapy well, with no difference in grade 2 or greater genitourinary and gastrointestinal toxicity (P = .8, P = .9, respectively). No patients receiving dose escalation required salvage cystectomy for invasive disease recurrence, compared with 2 patients who received standard dosing.

Preliminary evidence suggests efficacy of dose escalation with good tolerability, high rates of bladder preservation, and potentially lower rates of invasive recurrences compared with standard-dose radiation therapy. This study's findings support the need for further prospective studies to evaluate dose escalation as a technique to maximize the efficacy of TMT.