TOPLINE

In a phase 3 trial, hypofractionated salvage radiotherapy (RT) was no more effective than standard RT for patients with biochemical recurrence after radical prostatectomy. Over 4 years, biochemical progression-free survival rates were comparable, while the hypofractionated regimen came with a higher risk for late gastrointestinal (GI) toxicity.

METHODOLOGY

• Moderate hypofractionation is well established in definitive RT for prostate cancer, but evidence supporting it in the salvage setting remains limited. To address that gap, the phase 3 SHARE trial compared hypofractionated vs conventional salvage RT. 
• The randomized, open-label trial enrolled 316 patients at two medical centers in South Korea who had intermediate- to high-risk prostate cancer and biochemical recurrence after radical prostatectomy. 
• Patients were randomly assigned in a 1:1 ratio to receive either hypofractionated RT (65 Gy in 26 fractions) or conventional RT (66 Gy in 33 fractions), delivered to the prostate bed with elective pelvic nodal irradiation. Intensity-modulated RT with daily image guidance was used in all cases; endorectal balloons were used in 63% of patients. 
• The primary endpoint was biochemical progression-free survival, with secondary endpoints of distant metastasis-free survival, prostate cancer-specific survival, treatment-related toxicities, and patient-reported quality of life. 

TAKEAWAY

• After a median follow-up of 53 months, 4-year biochemical progression-free survival rates were 80.1% in the hypofractionated arm and 78.1% in the conventional arm, with no significant difference between groups (P = .88). 
• There were no differences in 4-year distant metastasis-free survival (91.7% in the hypofractionated arm and 91% in the conventional arm) or prostate cancer-specific survival (100% in both arms). 
• The 4-year cumulative incidence of late grade 2 or worse GI toxicity was higher in the hypofractionated arm, at 7.9% vs 0.7% (P < .01). Those events occurred primarily among patients treated without an endorectal balloon, and all cases resolved by last follow-up. Quality-of-life outcomes were comparable in both RT arms. 
• Concurrent androgen deprivation therapy (ADT) was associated with reduced biochemical progression (hazard ratio [HR], 0.15; P < .01), as were positive surgical margins (HR, 0.48; P = .01). 

IN PRACTICE

Although hypofractionated RT was not superior in this trial, the study authors wrote, “given the comparable oncologic outcomes, toxicity profiles, and quality-of-life measures, hypofractionated RT may be considered a viable alternative in the salvage setting.” They added that further research should examine whether endorectal balloons reduce GI toxicity in these patients.

SOURCE

The study, led by Youngju Song, MD, of the University of Ulsan College of Medicine in Seoul, South Korea, was published online in the Journal of Clinical Oncology.

LIMITATIONS

The results represent an interim analysis, and extended follow-up is needed to fully assess long-term efficacy and safety. The study was initiated before the adoption of PSMA PET/CT in South Korea. ADT use was left to the discretion of treating physicians, introducing heterogeneity that may confound the interpretation of efficacy.

DISCLOSURES

The study was supported by the Asan Institute for Life Science, Asan Medical Center. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.