Multicenter phase 3 trial of salvage hypofractionated versus standard radiotherapy for biochemical recurrence after radical prostatectomy

A multicenter phase 3 trial in South Korea compared hypofractionated radiotherapy (RT) versus conventional RT for treating biochemical recurrence of prostate cancer following radical prostatectomy. A total of 316 patients with intermediate- to high-risk prostate cancer were randomized to receive salvage RT with either 65 Gy in 26 fractions (HYPO) or 66 Gy in 33 fractions (CONV). RT was delivered to the prostate bed, with elective pelvic nodal irradiation performed at the discretion of radiation oncologists. IMRT with daily image guidance was used. The primary endpoint was biochemical progression-free survival (bPFS). A total of 151 patients (51.2%) received androgen deprivation therapy, and 202 (68.5%) underwent nodal irradiation. Endorectal balloons were used in 186 patients (63.1%). The median pre-RT PSA level was 0.36 ng/mL (IQR 0.24-0.49). The median follow-up was 52.6 months. The 4-year bPFS rates were 80.1% in the HYPO arm and 78.1% in the CONV arm; there also were no significant differences in 4-year rates of distant metastasis-free survival (91.7% versus 91.0%) and prostate cancer-specific survival (100% in both arms). The 4-year cumulative incidence of grade ≥ 2 GI toxicity was higher in the HYPO arm (7.9% versus 0.7%), predominantly among patients without an endorectal balloon; all cases were resolved by the last follow-up. Patient-reported quality-of-life outcomes were comparable. The authors conclude that bPFS at 4 years was not superior in the HYPO arm; however, given the comparable oncologic outcomes, toxicity profiles, and quality-of-life measures, hypofractionated RT may be considered a viable alternative in the salvage setting. Further research is needed to determine whether use of an endorectal balloon reduces GI toxicity.