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

Purpose 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. Methods 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. Results There are two randomized phase 3 trials comparing standard external beam radiotherapy with ultra-hypofractionated radiotherapy. HYPO-RT-PC compared 78 Gy in 39 fractions vs 42.7 Gy in 7 fractions (3D-CRT or IMRT) showing non-inferiority in 5-year biochemical recurrence-free survival and equivalent tolerability. PACE-B trial compared 78 Gy in 39-fraction or 62 Gy in 20-fraction vs 36.25 Gy in 5-fraction prostate SBRT, with no significant differences in toxicity outcomes at 2 years. 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. Conclusion 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.