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Radiotherapy (RT) delivery to the bladder is challenging as it is a mobile, deformable structure. Plan of the day (POD) adaptive image-guided RT and tumour boost dose escalation can optimise treatment of bladder cancer (BC). RAIDER aims to define a feasible, safe schedule for muscle-invasive BC using modern techniques.

RAIDER (ISRCTN 26779187) is an international phase II trial. Participants (pts) had unifocal T2-T4a urothelial BC and were randomised (1:1:2) to standard whole bladder RT (WBRT), standard dose adaptive tumour focused RT (SART) or dose-escalated adaptive tumour boost RT (DART). Two fractionation (f) schedules recruited independently. WBRT & SART dose was 64Gy/32f or 55Gy/20f and DART was 70Gy/32f or 60Gy/20f. For SART & DART, POD (small, medium, large) was chosen daily. Neo-adjuvant chemotherapy (NAC) and concomitant radiosensitising therapy (CTh) were permitted. Primary endpoint is the proportion of RT related CTCAE grade≥3 (G≥3) toxicity occurring 6-18 months (m) after RT. A non-comparative design planned to rule out >20% G≥3 toxicity in DART pts, required 57 evaluable DART pts in each fractionation cohort (90% power, 5% 1-sided alpha). Adverse events (AE) are treatment emergent with RT relatedness assessed blind to treatment. Toxicity analysis is by treatment received in the evaluable population (pts with at least one toxicity assessment 6-18m) and is independent by fractionation. Disease control data (3m local control assessed by cystoscopic biopsy; overall survival) are reported by allocated treatment group for both fractionation cohorts combined.

345 patients were randomised between Oct 2015 and Apr 2020: 46/41 WBRT, 46/41 SART and 90/81 DART pts in 32f/20f cohorts respectively. Baseline characteristics were balanced across groups: median age 73/72 years; 85/78% T2; 46/52% had NAC and 71%/70% CTh for 32f/20f cohorts. Median follow-up was 38.2 (IQR 26.2,50.2)/ 42.1m (IQR 35.6,50.1) in 32f/20f cohorts. 3588/6222 (57.6%) fractions delivered to SART and DART patients used adaptation (small or large plan). Late toxicity outcomes are shown in table. The RT related G3+ rate with 20f DART was 1/58 (90% CI 0.1,7.9) and 0/57 with 32f DART. 3m local control was achieved in 44/51 (86%) WBRT, 45/53 (85%) SART and 82/92(89%) DART.  2-year overall survival was WBRT 79% (95%CI 69-86%), SART 74% (95%CI 63,82%), DART 80% (95%CI 73,85%) (Fig 1).

G≥3 late toxicity was low across all treatment groups. DART was safe and feasible to deliver meeting preset toxicity thresholds. Local control for image-guided (chemo) RT was high across treatment groups. No difference in overall survival seen between groups.