Background
Phase III RCT (EORTC 22863). 415 patients with T1–T2 grade 3 or T3–T4 N0–1 M0 prostate adenocarcinoma, enrolled 1987–1995, at 30 European and Canadian centers. Randomized: RT alone (70 Gy/35 fx to pelvis + prostate boost) vs RT + immediate 3-year androgen suppression (goserelin monthly + cyproterone acetate 1 month). This is the landmark trial establishing 3-year long-term ADT combined with RT as the standard of care for high-risk localized prostate cancer.
Interventions and follow up
Arm A: Radiotherapy alone: 50 Gy whole pelvis + 20 Gy prostate boost (70 Gy total)
Arm B: RT + 3 years ADT (goserelin 3.6 mg q4wk starting day 1 of RT + cyproterone acetate 50 mg TID × 1 month before goserelin)
Primary endpoint: Clinical disease-free survival and overall survival
mFollow up: Median 9.1 year
Arm B: RT + 3 years ADT (goserelin 3.6 mg q4wk starting day 1 of RT + cyproterone acetate 50 mg TID × 1 month before goserelin)
Primary endpoint: Clinical disease-free survival and overall survival
mFollow up: Median 9.1 year
Results
10-year clinical DFS: 47.7% RT+ADT vs 22.7% RT alone, HR 0.42, P<.0001
10-year OS: 58.1% RT+ADT vs 39.8% RT alone, HR 0.60, P=.0004
10-year prostate cancer mortality: 10.3% RT+ADT vs 30.4% RT alone, HR 0.38, P<.0001
Cardiovascular mortality: No significant difference between arms
10-year OS: 58.1% RT+ADT vs 39.8% RT alone, HR 0.60, P=.0004
10-year prostate cancer mortality: 10.3% RT+ADT vs 30.4% RT alone, HR 0.38, P<.0001
Cardiovascular mortality: No significant difference between arms
Adverse events
Main adverse events: ADT: hot flashes (~78%), impotence (~80%), weight gain, osteoporosis. No significant increase in cardiovascular deaths with 3-year ADT in this trial (unlike the concern raised by D'Amico JAMA 2008). Two fractures reported in ADT arm. Late radiation toxicity grade 3+: ~5% in both arms.
Conclusions
Three-year ADT (goserelin) in combination with radiotherapy dramatically improves disease-free survival, overall survival, and disease-specific survival in patients with locally advanced (T3–T4) and high-risk prostate cancer. The absolute OS benefit of ~18% at 10 years is among the largest ever demonstrated by ADT addition in prostate cancer. This trial, together with RTOG 8610, established long-term ADT + RT as the standard for high-risk prostate cancer.
Key Limitations
Key Limitations: RT dose (70 Gy) is lower than the current standard (78 Gy), and 3D-CRT (not IMRT) was used; modern dose escalation may partially substitute for prolonged ADT in intermediate-risk disease. Three-year ADT is the maximum duration studied; whether 18 months vs 36 months is equally effective has been addressed by subsequent trials (DART 01/05 supporting 28 months). ADT-associated osteoporosis and cardiovascular risk are significant concerns not fully characterized in this trial.
Clinical Context
EORTC 22863 remains the definitive trial establishing 3-year long-term ADT + RT as standard for high-risk prostate cancer. Together with RTOG 9202 (Hanks 2003: 4-month vs 28-month ADT), these trials defined the ADT duration principle: high-risk disease requires 2–3 years. Modern practice adds docetaxel or androgen receptor pathway inhibitors (abiraterone, apalutamide, enzalutamide) with ADT + RT in very high-risk localized disease based on STAMPEDE, ENZAMET, and TITAN trials. RT dose has been escalated to 78 Gy (or hypofractionated equivalent) with IMRT.
References