In patients with high-risk prostate cancer receiving long-term androgen-deprivation therapy (ADT), pelvic and prostate external-beam radiation therapy (EBRT) at 80 Gy improved progression-free survival compared with conventional 70-Gy radiotherapy, according to findings from the multicenter phase III GETUG-AFU 18 study published in The Lancet Oncology. However, Hennequin et al noted that these data should be interpreted with caution because of the low number of events observed.
Radiotherapy at a total dose of 80 Gy “could be a potential option in this situation,” the investigators wrote, but “further research is needed to consolidate and confirm the benefit [of] dose-escalation in prostate cancer–specific survival and overall survival.”
Study Details
The study enrolled 505 men with high-risk prostate cancer treated at 25 centers in France. High-risk disease was defined as a prostate-specific antigen (PSA) level of 20 ng/mL or higher, a Gleason score of at least 8, or clinical stage T3 to T4. Patients were randomly assigned 1:1 by minimization and stratified by center and previous pelvic lymph node dissection to dose-escalated EBRT (80 Gy in 2-Gy fractions over 8 weeks) or standard-dose EBRT (70 Gy in 2-Gy fractions over 7 weeks), both combined with long-term ADT.
The primary endpoint was 5-year progression-free survival, defined as the time from randomization to the first evidence of biochemical disease progression—defined as PSA progression of 2 ng/mL above the nadir—or clinical progression, including local, regional, or metastatic disease. The analysis was conducted in the intention-to-treat population and required 197 events. Because 92 progression events had occurred by 5 years, the investigators also reported 10-year progression-free survival as a post-hoc analysis.
Key Findings
At a median follow-up of 9.5 years, the 5-year progression-free survival rate was 91.4% (95% confidence interval [CI] = 87.0%–94.4%) with dose-escalated radiotherapy vs 88.1% (95% CI = 83.2%–91.6%) with conventional-dose radiotherapy, and the 10-year rates were 83.6% (95% CI = 77.8%–88.0%) vs 72.2% (95% CI = 65.3%–78.0%), respectively (post hoc analysis; hazard ratio = 0.56, 95% CI = 0.40–0.78; P < .0001).
Grade 3 or higher adverse events at 6 months, reflecting acute toxicity, occurred in 60 (24%) patients in the dose-escalation group and 62 (25%) in the conventional-dose group. Sexual disorders (28 [11%] in the dose-escalation group vs 20 [8%] in the conventional-dose group) and bladder or urethra disorders (12 [5%] vs 19 [8%]) were the most frequently reported adverse events of grade 3 or higher.
At 5 years, late adverse events occurred in 118 (70%) of 168 patients treated with dose-escalated radiotherapy compared with 122 (73%) of 168 who received conventional-dose radiotherapy. Grade 3 or higher late toxicities were reported in 19 (8%) and 17 (7%) patients, respectively. The most common late grade 3 adverse event was bladder or urethral disorders, seen in seven (4%) patients in the dose-escalation group vs three (2%) in the conventional-dose group.
Serious adverse events occurred in nine (4%) patients in each group, with none considered related to treatment. No treatment-related deaths were reported.
“A dose of 80 Gy might be offered to patients with prostate cancer with a poor prognosis; however, additional research is needed to confirm this dose effect,” the investigators concluded.
Christophe Hennequin, MD, PhD, of Hôpital Saint-Louis, AP-HP, Paris, is the corresponding author of the article in The Lancet Oncology.
Disclosure: The study was funded by the French National Cancer Institute and AstraZeneca. For full disclosures of the study authors, visit thelancet.com.
