Two-fraction stereotactic ablative radiotherapy with simultaneous boost to MRI-defined dominant intra-prostatic lesion – Results from the 2SMART phase 2 trial

Purpose This is the first report of the 2SMART Phase II trial evaluating the safety of two-fraction stereotactic ablative radiotherapy (SABR) with focal boost to magnetic resonance imaging (MRI) defined dominant intra-prostatic lesion (DIL) for localised prostate cancer. Materials and methods Men with low or intermediate risk prostate cancer were eligible for the study. The gross tumour volume (GTV) was MRI-defined DIL, and the clinical target volume (CTV) was entire prostate gland. The planning target volume (PTV) was a 2 mm expansion anteroposterior and lateral, and 2.5 mm superoinferior. The prescribed dose was 32 Gy to GTV, and 26 Gy to CTV. Primary endpoint was minimal clinically important change (MCIC) in quality of life (QOL) within 3-months of SABR, assessed using the EPIC-26 questionnaire. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), PSA nadir, and biochemical failure (based on Phoenix criteria). Results Thirty men were enrolled in the study – 2 (7%) had low-risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range:39–49 months). The median PSA nadir was 0.25 ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. Ten (33%), six (20%), and three (10%) men had acute MCIC in urinary, bowel, and sexual QOL domains respectively. No acute or late grade ≥ 3 urinary or bowel toxicities were observed. Conclusion This novel protocol of two-fraction prostate SABR with MRI-defined DIL boost is a safe approach for dose-escalation, with minimal impact on acute QOL and no grade ≥ 3 toxicities.