Background
Phase III, open-label, randomized trial. 1,523 patients with prostate cancer receiving post-prostatectomy radiotherapy randomized to short-term ADT (6 months) vs long-term ADT (24 months). Patients had pT3-T4 disease, positive surgical margins, or PSA persistence/recurrence after radical prostatectomy. Primary endpoint pre-specified as metastasis-free survival (MFS).
Interventions and follow up
Arm A: Postoperative RT + short-term ADT (6 months; LHRH agonist or antagonist)
Arm B: Postoperative RT + long-term ADT (24 months)
Primary endpoint: Metastasis-free survival (MFS)
mFollow up: 10 year
Arm B: Postoperative RT + long-term ADT (24 months)
Primary endpoint: Metastasis-free survival (MFS)
mFollow up: 10 year
Results
10-yr MFS: 71.9% (short) vs 78.1% (long), HR 0.773 (95% CI 0.616–0.971), P=.029
10-yr OS: 76.3% vs 79.8%, HR 0.843 (95% CI 0.660–1.076), P=.17
10-yr PCSM: 10.1% vs 7.6%, HR 0.727 (95% CI 0.495–1.066)
10-yr OS: 76.3% vs 79.8%, HR 0.843 (95% CI 0.660–1.076), P=.17
10-yr PCSM: 10.1% vs 7.6%, HR 0.727 (95% CI 0.495–1.066)
Adverse events
Main adverse events: Grade ≥3 toxicity: 14% (short) vs 19% (long). Long-term ADT associated with higher rates of sexual dysfunction, hot flushes, fatigue, and bone density loss. No significant difference in cardiovascular events.
Conclusions
Long-term ADT (24 months) significantly improved 10-year MFS compared to short-term ADT (6 months) when combined with postoperative RT, supporting prolonged hormone therapy as a component of post-prostatectomy treatment for high-risk disease. OS was not significantly different, likely due to insufficient follow-up and competing mortality.
Key Limitations
Key Limitations: No RT-alone or ADT-alone arm, precluding assessment of RT vs ADT contributions. RT techniques were heterogeneous across 26 years of trial conduct (1997–2023). MFS is a surrogate endpoint without definitive OS validation. Optimal patient selection for long vs short ADT (e.g., Gleason score, genomic risk) is undefined. Modern staging with PSMA-PET was not used, and some patients may have had occult oligometastatic disease.
Clinical Context
Establishes 24-month ADT with postoperative RT as the preferred duration in high-risk prostate cancer post-prostatectomy. Complements the RADICALS-RT trial (RT timing) and GETUG-AFU 16 (6 vs 18 months ADT with salvage RT). ESMO and NCCN guidelines support long-term ADT with adjuvant/salvage RT in high-risk settings.
References
References: Parker CC et al, Lancet 2024 (RADICALS-HD)