Dose-escalated Adaptive Radiotherapy for Bladder Cancer: Results of the Phase 2 RAIDER Randomised Controlled Trial
- Author(s)
- Huddart, R; Hafeez, S; Griffin, C; Choudhury, A; Foroudi, F; Syndikus, I; Hindson, B; Webster, A; McNair, H; Birtle, A; Varughese, M; Henry, A; McLaren, DB; Parikh, O; Nikapota, A; Tang, C; Patel, E; Miles, E; Warren-Oseni, K; Kron, T; Hill, C; Philipps, L; Vassallo-Bonner, C; Cheung, KC; Gribble, H; Lewis, R; Hall, E;
- Journal Title
- European Urology
- Publication Type
- Online publication before print
- Abstract
- BACKGROUND AND OBJECTIVE: Delivering radiotherapy to the bladder is challenging as it is a mobile, deformable structure. Dose-escalated adaptive image-guided radiotherapy could improve outcomes. RAIDER aimed to demonstrate the safety of such a schedule. METHODS: RAIDER is an international phase 2 noncomparative randomised controlled trial (ISRCTN26779187). Patients with unifocal T2-T4a urothelial bladder cancer were randomised (1:1:2) to standard whole bladder radiotherapy (WBRT), standard-dose adaptive radiotherapy (SART), or dose-escalated adaptive radiotherapy (DART). Two fractionation (f) schedules recruited independently. WBRT and SART dose was 55 Gy/20f or 64 Gy/32f, and DART dose was 60 Gy/20f or 70 Gy/32f. For SART and DART, a radiotherapy plan (small, medium, or large) was chosen daily. The primary endpoint was the proportion of patients with radiotherapy-related late Common Terminology Criteria for Adverse Events grade ≥3 toxicity; the trial was designed to rule out >20% toxicity with DART. KEY FINDINGS AND LIMITATIONS: A total of 345 patients were randomised between October 2015 and April 2020: 41/46 WBRT, 41/46 SART, and 81/90 DART patients in the 20f/32f cohorts, respectively. The median age was 72/73 yr; 78%/85% had T2 tumours, 46%/52% had neoadjuvant chemotherapy, and 70%/71% had radiosensitising therapy. The median follow-up was 42.1/38.2 mo. Sixty-six of 77 (86%) 20f and 74 of 82 (90%) 32f participants planned for DART met the mandatory medium plan dose constraints. Radiotherapy-related grade ≥3 toxicity was reported in one of 58 patients (90% confidence interval [CI] 0.1, 7.9) with 20f DART and zero of 56 patients with 32f DART. Two-year overall survival was 77% (95% CI 69, 82) for WBRT + SART and 80% (95% CI 73, 85) for DART (hazard ratio = 0.84, 95% CI 0.59, 1.21, p = 0.4). Thirteen of 345 (3.8%) participants had salvage cystectomy. CONCLUSIONS AND CLINICAL IMPLICATIONS: Grade ≥3 late toxicity was low. DART was safe and feasible to deliver, meeting preset toxicity thresholds. Disease-related outcomes are promising for dose-escalated treatments, with a low salvage cystectomy rate and overall survival similar to that seen in cystectomy cohorts.
- Keywords
- Adaptive radiotherapy; Image-guided radiotherapy; Muscle-invasive bladder cancer; Radiotherapy; Randomised controlled trial
- Department(s)
- Physical Sciences
- Publisher's Version
- https://doi.org/10.1016/j.eururo.2024.09.006
- Open Access at Publisher's Site
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Creation Date: 2024-10-23 03:01:16
Last Modified: 2024-10-23 03:12:18