The march toward single-fraction stereotactic body radiotherapy for localized prostate cancer-Quo Vadimus?

Abstract

Stereotactic body radiotherapy (SBRT) is an emerging treatment option for localized prostate cancer. There is increasing interest to reduce the number of fractions for prostate SBRT. We provide a narrative review and summary of prospective trials of different fractionation schedules for prostate SBRT, focusing on efficacy, toxicities, and quality of life outcomes. There are two randomized phase 3 trials comparing standard external beam radiotherapy with ultra-hypofractionated radiotherapy. HYPO-RT-PC compared 78Gy in 39 fractions vs 42.7Gy in 7 fractions (3D-CRT or IMRT) showing non-inferiority in 5-year biochemical recurrence-free survival and equivalent tolerability. PACE-B trial compared 78Gy in 39-fraction or 62Gy in 20-fraction vs 36.25Gy in 5-fraction prostate SBRT, with no significant differences in toxicity outcomes at 2years. Five-year efficacy data for PACE-B are expected in 2024. Five-fraction prostate SBRT is currently the most common and well-established fractionation schedule with multiple prospective phase 2 trials published to date. There is more limited data on 1-4 fraction prostate SBRT. All fractionation schedules had acceptable toxicity outcomes. Experience from a high-dose-rate brachytherapy randomized trial showed inferior efficacy with single-fraction compared to two-fraction brachytherapy. Hence, caution should be applied in adopting single-fraction prostate SBRT. Two-fraction SBRT is likely the shortest fractionation schedule that maintains the therapeutic ratio. Several randomized trials currently recruiting will likely provide us with more definite answers about whether two-fraction prostate SBRT should become a standard-of-care option. Enrollment of eligible patients into these trials should be encouraged.