Dose Escalated Adaptive Bladder Radiotherapy: Clinical Outcomes of a Phase I Study

Purpose/Objectives We determine the maximum tolerated tumour focused dose (MTD) for the radical treatment of muscle invasive bladder cancer (MIBC) enabled by image guided adaptive radiotherapy (IGART) and long-term clinical outcomes. Materials/Methods : Fifty-nine patients with T2-T4aN0M0 unifocal urothelial MIBC suitable for daily radical radiotherapy were recruited prospectively to an ethics approved protocol (XX). The uninvolved bladder (PTVbladder) was planned to 52Gy in 32 fractions (f). The bladder tumour (PTVtumour) was planned to an assigned dose level of 68, 70, 72, or 74Gy. If organ at risk (OAR) dose constraints were violated, then PTVtumour was planned to 64Gy. Dose level allocation was determined by concurrent toxicity assessment of all previous patients recruited. Acute toxicity was evaluated using CTCAE v3.0; late toxicity was evaluated using RTOG criteria. The MTD was predefined as the highest dose level with estimated probability of ≤ 15% ≥G3 late toxicity and observed rate <50% acute G3 and <10% acute G4 toxicity. Results Twenty-six patients were assigned to 68Gy, of whom 6 were planned to 64Gy; 29 patients were assigned to 70Gy of whom 1 was planned to 68Gy, 2 patients were assigned and planned to 72Gy; no patients were assigned to 74Gy. Three patients did not complete treatment as planned, of whom only 1 patient stopped treatment because dose limiting toxicity occurred. The MTD was 70Gy. Acute genitourinary (GU) and gastrointestinal (GI) G3 acute toxicity was seen in 19% and 7% patients respectively. No grade 4 GU or GI toxicity was seen. Late toxicity (any) G3 and G4 was seen in 14% and 2% patients respectively. The 5-year overall survival was 58% (95% CI 44-71%). The bladder preservation rate was 89% (95% CI, 88 to 96%) with 6 patients not retaining native bladder function. Conclusion Bladder tumour focused dose escalation to 70Gy using IGART is feasible with acceptable toxicity. This dose level has been evaluated in a phase II randomised control trial (XXXXX).