Two Versus Five-Fraction Magnetic Resonance-Guided Adaptive Radiotherapy with DOminant-TArgeted Boost in Localized Prostate Cancer (DOTA-2): Interim Acute Toxicity Analysis of the Phase II Randomised Trial

Abstract

Aims: DOminant-TArgeted Boost in Localized Prostate Cancer (DOTA-2) is a phase II randomised controlled trial comparing two ultra-hypofractionated radiotherapy with dominant intraprostatic lesion (DIL) boost: 26 Gy/2F, 32 Gy to DIL vs 36.25 Gy/5F, 40 Gy to DIL, without androgen deprivation therapy (ADT), for prostate cancer. Materials and methods: Patients with low- to favourable-intermediate-risk prostate cancer were randomly assigned to receive either 2 fractions or 5 fractions. Magnetic resonance-guided adaptive radiotherapy (MRgART) was delivered using the Unity® MR-Linac with the adapt-to-shape workflow for every fraction. The primary endpoint was cumulative grade ≥2 acute genitourinary (GU) and gastrointestinal (GI) toxicity. Secondary endpoints included quality of life in the urinary and sexual domains. An interim analysis of acute GU and GI toxicities was conducted on the first 22 patients from the total planned cohort of 44. Results: Patients were randomly assigned to either the 2-fraction (N = 10) or 5-fraction stereotactic body radiotherapy (SBRT) (N = 12), stratified by risk group, prostate volume, and DIL location. The median follow-up time was 16 weeks. The cumulative worst acute grade ≥2 GU toxicity was reported in 2/10 (20%) patients in the 2-fraction group vs 4/12 (33.3%) in the 5-fraction group (P = 0.48), with no cases of grade ≥3 acute GU toxicity. No grade ≥2 acute GI toxicity was observed in either arm. The two groups had no significant difference in International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) scores. Conclusion: Two-fraction SBRT with a DIL boost, delivered using MRgART without ADT, demonstrated acceptable acute GU and GI toxicity in this interim analysis, suggesting the feasibility of continuing the investigation.