The phase II PEACE V-STORM trial has established elective nodal radiotherapy (ENRT) as a promising treatment approach for patients with oligorecurrent prostate cancer, demonstrating superior metastasis-free survival compared to metastasis-directed therapy alone. The international multicenter study, published in The Lancet Oncology, represents the first randomized trial to compare local treatment strategies for PET-detected nodal recurrences in prostate cancer.
Trial Design and Patient Population
The open-label trial enrolled 190 evaluable patients with PET-detected pelvic nodal oligorecurrence (up to five nodes) following radical local treatment. Patients were recruited from sites across Australia, Belgium, Italy, Norway, Spain, and Switzerland between June 2018 and April 2021. Participants were randomly assigned to receive either ENRT (n = 93) or metastasis-directed therapy (MDT) (n = 97).
Patients in the ENRT group received a 45 Gy dose in 25 fractions to the pelvis, with a simultaneous integrated boost of 65 Gy to the PET-positive nodes or salvage lymph node dissection, combined with 6 months of androgen-deprivation therapy. The MDT group received salvage nodal dissection or stereotactic body radiotherapy (30 Gy in three fractions every other day), also with 6 months of androgen-deprivation therapy.
Primary Efficacy Outcomes
At a median follow-up of 50 months, ENRT demonstrated clinically meaningful improvements in metastasis-free survival. The 4-year metastasis-free survival was 76% (80% confidence interval = 69%-81%) in the ENRT group versus 63% (80% CI = 56%-69%) in the MDT group (hazard ratio = 0.62, 80% CI = 0.44-0.86, P = .063).
Secondary Endpoints Show Consistent Benefits
The trial revealed significant improvements across multiple secondary endpoints favoring ENRT. At 4 years, biochemical relapse-free survival was 57% (80% CI = 50%-64%) in the ENRT group compared to 41% (80% CI = 34%-47%) in the MDT group (HR = 0.62, 80% CI = 0.48-0.80, P = .014).
Locoregional control showed particularly striking differences, with locoregional relapse-free survival reaching 85% (80% CI = 80%-90%) in the ENRT group versus 62% (80% CI = 55%-69%) in the MDT group (HR = 0.45, 80% CI = 0.31-0.65, P = .0047).
Androgen-deprivation therapy-free survival also favored ENRT, with rates of 77% (80% CI = 70%-82%) versus 60% (80% CI = 53%-67%) in the MDT group (HR = 0.60, 80% CI = 0.43-0.83, P = .049).
Safety Profile
The safety analysis revealed manageable toxicity profiles for both treatment approaches. At 4 years, grade ≥2 genitourinary adverse events occurred in 31% of the ENRT group versus 28% of the MDT group, while grade ≥2 gastrointestinal adverse events occurred in 9% versus 7%, respectively.
The most common grade 3 adverse events were urinary incontinence (10% vs 6%) and diarrhea (2% vs 1%). Notably, no grade 4 events were observed in either treatment group, and no treatment-related deaths were reported throughout the study period.
Clinical Implications
According to the investigators, "To our knowledge, this is the first randomised trial for metachronous PET-detected nodal recurrences comparing two local treatment approaches (MDT and ENRT) in combination with 6 months of androgen-deprivation therapy. By showing an improved metastasis-free survival with ENRT, this trial establishes ENRT as a potential standard treatment approach, awaiting a phase III trial confirming these results."
The study's findings suggest that ENRT may offer a more comprehensive approach to treating oligorecurrent prostate cancer by addressing both visible disease and potential microscopic disease in the regional lymph nodes. This broader treatment field appears to translate into improved disease control across multiple clinical endpoints while maintaining an acceptable safety profile.
