Dose-escalated Adaptive Radiotherapy for Bladder Cancer: Results of the Phase 2 RAIDER Randomised Controlled Trial

Area of Science:

• Radiation Oncology
• Urologic Oncology
• Clinical Trials

Background:

• Radiotherapy for bladder cancer is challenging due to the bladder's mobility and deformability.
• Adaptive image-guided radiotherapy offers potential for improved outcomes in bladder cancer treatment.
• The RAIDER trial investigated the safety of dose-escalated adaptive radiotherapy schedules.

Purpose of the Study:

• To assess the safety and feasibility of dose-escalated adaptive radiotherapy (DART) for urothelial bladder cancer.
• To determine the rate of radiotherapy-related late toxicity (grade ≥3) in patients receiving DART.
• To evaluate disease-related outcomes, including overall survival and salvage cystectomy rates.

Main Methods:

• An international phase 2 noncomparative randomized controlled trial (RAIDER) involving 345 patients with unifocal T2-T4a urothelial bladder cancer.
• Patients were randomized to standard whole bladder radiotherapy (WBRT), standard-dose adaptive radiotherapy (SART), or dose-escalated adaptive radiotherapy (DART) with two fractionation schedules (20f or 32f).
• Daily plan adaptation was used for SART and DART, with the primary endpoint being the proportion of patients experiencing grade ≥3 late toxicity.

Main Results:

• Radiotherapy-related grade ≥3 late toxicity was low: 1.7% (1/58) for 20f DART and 0% (0/56) for 32f DART.
• Two-year overall survival was 77% for WBRT+SART and 80% for DART, with no statistically significant difference.
• The salvage cystectomy rate was 3.8% across all participants.

Conclusions:

• Dose-escalated adaptive radiotherapy (DART) is safe and feasible for bladder cancer treatment, meeting predefined toxicity thresholds.
• Disease-related outcomes for DART are promising, with overall survival rates comparable to cystectomy cohorts.
• The low rate of salvage cystectomy suggests DART may be an effective bladder-sparing treatment option.