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.
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.
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.
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.
European urology. 2024 Sep 24 [Epub ahead of print]
Robert Huddart, Shaista Hafeez, Clare Griffin, Ananya Choudhury, Farshad Foroudi, Isabel Syndikus, Benjamin Hindson, Amanda Webster, Helen McNair, Alison Birtle, Mohini Varughese, Ann Henry, Duncan B McLaren, Omi Parikh, Ashok Nikapota, Colin Tang, Emma Patel, Elizabeth Miles, Karole Warren-Oseni, Tomas Kron, Courtney Hill, Lara Philipps, Catalina Vassallo-Bonner, Ka Ching Cheung, Hannah Gribble, Rebecca Lewis, Emma Hall
The Institute of Cancer Research, Sutton, UK; The Royal Marsden NHS Foundation Trust, Sutton, UK. Electronic address: ., The Institute of Cancer Research, Sutton, UK; The Royal Marsden NHS Foundation Trust, Sutton, UK., The Institute of Cancer Research, Sutton, UK., The Christie NHS Foundation Trust, The Christie, Manchester, UK., Austin Health, Heidelberg, Victoria, Australia., The Clatterbridge Cancer Centre, Bebington, UK., Canterbury Regional Cancer and Haematology Service, Christchurch Hospital, Christchurch, New Zealand., University College Hospital, London, UK; University College Hospitals NHS Foundation Trust, University College Hospital, London, UK., Lancashire Teaching Hospitals NHS Trust, Rosemere Cancer Centre, Royal Preston Hospital, Preston, UK; University of Manchester, Manchester, UK; University of Central Lancashire, Preston, UK., Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital, Exeter, UK., University of Leeds, Leeds, UK; Leeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UK., NHS Lothian, Western General Hospital, Edinburgh, UK., Lancashire Teaching Hospitals NHS Trust, Rosemere Cancer Centre, Royal Preston Hospital, Preston, UK., Brighton and Sussex University Hospitals NHS Trust, Royal Sussex County Hospital, Brighton, UK., Sir Charles Gairdner Hospital, Nedlands, WA, Australia., National Radiotherapy Trials Quality Assurance Group (RTTQA), Mount Vernon Hospital, Middlesex, UK., Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., TROG Cancer Research, Waratah, NSW, Australia.