Dose-Escalated Radiotherapy Shows Promise in High-Risk Prostate Cancer Management

A recent multicenter study published in The Lancet Oncology has provided insight into the potential benefits of dose-escalated external-beam radiation therapy (EBRT) in conjunction with long-term androgen-deprivation therapy (ADT) for patients with high-risk prostate cancer. The phase III GETUG-AFU 18 trial highlighted the improved progression-free survival linked to an 80 Gy radiation dose compared to the conventional 70 Gy regimen, though researchers noted the results should be interpreted cautiously due to the limited number of progression events.

In France, 505 men with high-risk prostate cancer participated in this trial conducted across 25 centers. Eligibility required 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 disease. Participants received either a dose-escalated EBRT of 80 Gy over eight weeks or a standard 70 Gy over seven weeks, both alongside long-term ADT. Randomization was stratified by center and prior pelvic lymph node dissection.

The primary endpoint was the 5-year progression-free survival, defined by biochemical disease progression or clinical progression, including local, regional, or metastatic disease. The initial analysis required 197 events, yet only 92 were observed at the 5-year mark, prompting a post-hoc analysis to evaluate 10-year progression-free survival outcomes.

Findings demonstrated a 5-year progression-free survival of 91.4% with the 80 Gy regimen, versus 88.1% for the 70 Gy group. At 10 years, these figures were 83.6% and 72.2%, respectively, with a hazard ratio of 0.56, indicating a significant advantage for the dose-escalated therapy (P < .0001).

Adverse events, both acute and late, were prominent in both groups. Acute grade 3 or higher events affected 24% of the dose-escalation group and 25% of the conventional group. Sexual and bladder or urethral disorders were the most frequent severe side effects. By 5 years, late grade 3 or higher toxicities were reported in 8% of the dose-escalation group versus 7% in the conventional group, with bladder or urethral issues being most common.

Despite nine serious adverse events reported in each group, none were treatment-related, and no deaths were attributed to the intervention. The authors, including lead author Christophe Hennequin, MD, PhD, from Hôpital Saint-Louis, Paris, conclude that while an 80 Gy dose may be advisable for patients with a poor prognosis, further research is necessary to confirm its survival benefits.