According to interim results of the phase III SHARE trial reported by Song et al in the Journal of Clinical Oncology, hypofractionated salvage radiotherapy produced similar 4-year oncologic outcomes to conventional radiotherapy among patients with biochemical recurrence after radical prostatectomy, although late gastrointestinal (GI) toxicity was more frequent with hypofractionation. Researchers conducted the randomized trial to compare the efficacy and safety of hypofractionated vs conventional fractionation specifically in the salvage setting, where prospective evidence has been limited.
Study Details
Between August 2019 and November 2021, the open-label, multi-institutional trial randomly assigned 316 patients with intermediate- to high-risk prostate cancer and biochemical recurrence after radical prostatectomy to hypofractionated radiotherapy at 65 Gy in 26 fractions or conventional radiotherapy at 66 Gy in 33 fractions. Eligible patients had a post-prostatectomy prostate-specific antigen (PSA) level of ≤ 1.0 ng/mL, with no evidence of gross disease in the prostate bed, lymph nodes, or distant sites. A total of 295 patients were included in the modified intention-to-treat analysis.
Radiotherapy was delivered to the prostate bed using intensity-modulated radiotherapy and daily image guidance. Elective pelvic nodal irradiation and androgen-deprivation therapy were permitted at the discretion of treating physicians. Overall, 68.5% of patients received elective nodal irradiation, 51.2% received concurrent androgen-deprivation therapy, and 63.1% were treated using an endorectal balloon. The median pre-radiotherapy PSA level was 0.36 ng/mL. The primary endpoint was biochemical progression-free survival.
Key Results
After a median follow-up of 52.6 months, biochemical progression occurred in 29 patients in the hypofractionated group and 31 patients in the conventional group. The 4-year biochemical progression-free survival rates were 80.1% and 78.1%, respectively (P = .88). Four-year distant metastasis–free survival was also similar at 91.7% vs 91.0% (P = .94), and prostate cancer–specific survival was 100% in both groups. Undetectable PSA levels were achieved in 76.6% and 76.7% of patients, respectively.
Acute grade 2 genitourinary (GU) toxicity was observed in 7.6% of patients receiving hypofractionated radiotherapy and 6.0% receiving conventional radiotherapy, whereas acute grade 2 GI toxicity occurred in 2.8% and 6.0%, respectively. No acute grade ≥ 3 toxicities were reported. At 4 years, the cumulative incidence of late grade ≥ 2 GU toxicity was similar between groups (12.0% vs 10.4%, P = .62), but late grade ≥ 2 GI toxicity was higher with hypofractionation (7.9% vs 0.7%, P < .01).
The difference in late GI toxicity was primarily observed among patients treated without an endorectal balloon. Among those without balloon use, the 4-year incidence of late grade ≥ 2 GI toxicity was 15.3% with hypofractionated radiotherapy vs 1.9% with conventional radiotherapy (P = .02). Patient-reported urinary and bowel quality-of-life outcomes did not differ significantly between the treatment groups.
The investigators concluded: “[Biochemical progression-free survival] was not superior in the [hypofractionated] arm at 4 years. However, given the comparable oncologic outcomes, toxicity profiles, and quality-of-life measures, hypofractionated [radiotherapy] may be considered a viable alternative in the salvage setting. Further research is needed to determine whether the use of an endorectal balloon reduces GI toxicity.”
Young Seok Kim, MD, PhD, of the Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the Asan Institute for Life Science, Asan Medical Center. For full disclosures of the study authors, visit ascopub.org.
