As reported in The Lancet Oncology by Sargos et al, the French phase III GETUG-AFU 17 trial has shown no event-free survival benefit for adjuvant radiotherapy vs salvage radiotherapy—both with short-term androgen-deprivation therapy (ADT)—after radical prostatectomy in men with localized prostate cancer.
In the multicenter trial, 424 patients were randomly assigned between March 2008 and June 2016 to receive adjuvant radiotherapy (n = 212) or salvage radiotherapy triggered by a prostate-specific antigen (PSA) level > 0.2 ng/mL confirmed after 4 weeks (n = 212). All patients received 6 months of triptorelin via intramuscular injection every 3 months. Patients with pathologic stage pT3a, pT3b, or pT4a (with bladder neck invasion), pNx (without pelvic lymph nodes dissection), or pN0 (with negative lymph nodes dissection) disease and positive surgical margins were eligible for the study.
The primary endpoint was event-free survival in the intent-to-treat population. Event-free survival events consisted of disease relapse (locoregional or metastatic), biochemical progression (PSA level ≥ 0.4 ng/mL at least 6 months after completing adjuvant or salvage radiotherapy or PSA level ≥1 ng/mL at any time), or death.
Planned enrollment was 718 patients, with 359 in each group. However, in May 2016, the independent data monitoring committee recommended early termination of enrollment due to unexpectedly low event rates. The primary analysis was thus statistically underpowered.
At database lock in December 2019, median follow-up was 75 months. In the salvage radiotherapy group, 115 (54%) of 212 patients initiated study treatment after biochemical relapse. A total of 205 (97%) of 212 patients started treatment in the adjuvant group. The median time from random assignment to radiotherapy was 1.1 months in the adjuvant radiotherapy group and 23 months in the salvage radiotherapy group.
Event-free survival at 5 years was 92% in the adjuvant radiotherapy group vs 90% in the salvage radiotherapy group (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.48–1.36, P = .42).
Metastasis-free survival data were not mature for comparison between groups. Metastatic progression events occurred in three patients in the adjuvant radiotherapy group vs eight in the salvage radiotherapy group. Death occurred in 7% of patients in the adjuvant radiotherapy group and 5% of the salvage radiotherapy group, with two deaths in each group being due to prostate cancer. Overall survival at 5 years was 96% vs 99% (HR = 1.60, 95% CI = 0.71–3.60, P = .25).
Acute grade ≥ 3 toxicity occurred in 3% of the adjuvant radiotherapy group vs 2% of the salvage radiotherapy group. Late grade ≥ 2 toxicity occurred in 59% vs 22%. Late gastrointestinal grade ≥ 2 toxicity occurred in 8% vs 5% (P = .24); late genitourinary grade ≥ 2 adverse events occurred in 27% vs 7% (P < .0001). Late erectile dysfunction of grade ≥ 2 occurred in 28% vs 8% (P < .0001).
The investigators concluded, “Although our analysis lacked statistical power, we found no benefit for event-free survival in patients assigned to adjuvant radiotherapy compared with patients assigned to salvage radiotherapy. Adjuvant radiotherapy increased the risk of genitourinary toxicity and erectile dysfunction. A policy of early salvage radiotherapy could spare men from overtreatment with radiotherapy and the associated adverse events.”
Paul Sargos, MD, of the Department of Radiotherapy, Institut Bergonié, Bordeaux, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the French Health Ministry and Ipsen. For full disclosures of the study authors, visit thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.