Background
Phase III RCT (EORTC 22911). 1,005 patients with cT0–T3 pN0 prostate cancer (WHO PS 0–1) from 37 European institutions. Eligible after radical prostatectomy with pathologic evidence of extraprostatic extension or positive surgical margins. Median follow-up 10.6 years.
Interventions and follow up
Arm A: Postoperative radiotherapy 60 Gy conventional fractionation to the surgical bed (n=502)
Arm B: Wait-and-see until biochemical progression (PSA >0.2 μg/L confirmed twice ≥2 weeks apart), then salvage RT (n=503)
Primary endpoint: Biochemical progression-free survival
mFollow up: 10.6 year
Arm B: Wait-and-see until biochemical progression (PSA >0.2 μg/L confirmed twice ≥2 weeks apart), then salvage RT (n=503)
Primary endpoint: Biochemical progression-free survival
mFollow up: 10.6 year
Results
Biochemical PFS: Significantly improved with postoperative RT (HR 0.49, 95% CI 0.41–0.59, P<.0001); 39.4% had progression in RT arm vs 61.8% in WS arm
Clinical PFS: Not significantly maintained at 10 years
OS: No significant benefit reported
Clinical PFS: Not significantly maintained at 10 years
OS: No significant benefit reported
Adverse events
Main adverse events: Late adverse events (any type, any grade) at 10 years: 70.8% (postoperative RT) vs 59.7% (WS), P=.001. Higher rates of GI and GU late effects in irradiated arm.
Conclusions
Immediate postoperative radiotherapy significantly improved biochemical progression-free survival and local control compared with wait-and-see at 10.6-year median follow-up. However, improvements in clinical progression-free survival were not maintained, and no OS benefit was demonstrated.
Key Limitations
Key Limitations: No OS benefit. Higher late toxicity with adjuvant vs. deferred RT limits enthusiasm for universal adjuvant approach. 60 Gy dose is suboptimal by current standards. Exploratory analysis suggested possible benefit in younger patients and R1 cases, but potential detriment in patients ≥70 years. RAVES and RADICALS-RT subsequently demonstrated equivalence of adjuvant and early salvage approaches.
Clinical Context
EORTC 22911 is the largest of three foundational adjuvant RT trials in pT3 prostate cancer. The absence of OS benefit combined with increased late toxicity contributed to contemporary practice guidelines recommending early salvage RT over universal adjuvant RT. ESMO and AUA guidelines now support observation with early salvage at PSA rise.
References