Top Line: Hypofractionation of post-prostatectomy radiation has never really taken off due to concern of worse late side effects.
The Study: GU003 suggested moderate-hypofractionation was ok at two years, granting that’s probably not late enough to judge. The similarly-designed phase 3 SHARE trial randomized 316 men with biochemical recurrence after prostatectomy to moderately-hypofractionated (65 Gy/26) versus conventional (66 Gy/33) salvage radiation with modern IMRT and daily image guidance. It failed to demonstrate its intended goal of superior biochemical control with moderate-hypofractionation: biochemical progression-free survival at 4 years was virtually identical: 80% vs 78% with conventional fractionation. Survival free from distant mets was similarly comparable (92% vs 91%), as was patient-reported urinary and bowel quality-of-life. The median pre-radiation PSA was only 0.36 ng/mL, and eligibility capped PSA at 1.0 ng/mL, reflecting contemporary early-salvage practice. Moreover, 51% received ADT and 68.5% received elective pelvic nodal RT, both of which may have contributed to the excellent overall disease control. Notably, and in line with previous data, late grade 2+ GI events were significantly higher with moderate-hypofractionation (8% vs <1%), primarily rectal bleeding, although all reported events had resolved by the last follow-up. Finally, the authors note the numbers suggest use of an endorectal balloon (performed at physician discretion) may ameliorate the increased risk of late GI events following moderate hypofractionation.
TBL: In the most modern trial to date, moderately-hypofractionated salvage prostate-bed radiation failed to improve biochemical control with an early signal for increased risk of late rectal bleeding. | Song, J Clin Oncol 2026
The Study: GU003 suggested moderate-hypofractionation was ok at two years, granting that’s probably not late enough to judge. The similarly-designed phase 3 SHARE trial randomized 316 men with biochemical recurrence after prostatectomy to moderately-hypofractionated (65 Gy/26) versus conventional (66 Gy/33) salvage radiation with modern IMRT and daily image guidance. It failed to demonstrate its intended goal of superior biochemical control with moderate-hypofractionation: biochemical progression-free survival at 4 years was virtually identical: 80% vs 78% with conventional fractionation. Survival free from distant mets was similarly comparable (92% vs 91%), as was patient-reported urinary and bowel quality-of-life. The median pre-radiation PSA was only 0.36 ng/mL, and eligibility capped PSA at 1.0 ng/mL, reflecting contemporary early-salvage practice. Moreover, 51% received ADT and 68.5% received elective pelvic nodal RT, both of which may have contributed to the excellent overall disease control. Notably, and in line with previous data, late grade 2+ GI events were significantly higher with moderate-hypofractionation (8% vs <1%), primarily rectal bleeding, although all reported events had resolved by the last follow-up. Finally, the authors note the numbers suggest use of an endorectal balloon (performed at physician discretion) may ameliorate the increased risk of late GI events following moderate hypofractionation.
TBL: In the most modern trial to date, moderately-hypofractionated salvage prostate-bed radiation failed to improve biochemical control with an early signal for increased risk of late rectal bleeding. | Song, J Clin Oncol 2026