Prostate Cancer · Medical · Salvage RT + Antiandrogen
NRG/RTOG 9601
After prostatectomy with PSA recurrence, does long-term antiandrogen therapy added to salvage radiotherapy improve long-term survival?
Tumour site
Prostate Cancer
Discipline
Medical
Clinical setting
Salvage RT + Antiandrogen
Evidence type
Comparative clinical evidence
Absolute Effect
RTOG 9601 randomized men receiving salvage prostate-bed radiotherapy to 24 months of bicalutamide or placebo. At 12 years, overall survival was 76.3% with bicalutamide versus 71.3% with placebo (HR 0.77, 95% CI 0.59–0.99). The 2025 long-term analysis reported 18-year OS of 53% versus 43% (adjusted HR 0.82, 95% CI 0.67–1.00; one-sided P=.025). Baseline PSA modifies the magnitude of benefit and toxicity trade-off.
NNT / NNH: Calculated only when a defensible fixed-time absolute event difference is available. Hazard ratios alone are not converted into NNT.
Clinical interpretation
Long-term bicalutamide added to salvage RT improved average outcomes in the trial population, but benefit varies by presalvage PSA and toxicity makes universal 24-month treatment inappropriate.
Limitations
The regimen predates many modern salvage approaches; the low-PSA subgroup analysis and contemporary risk assessment are essential before extrapolating the average benefit.
At 12 years, overall survival was 76.3% with salvage RT plus 24 months of bicalutamide versus 71.3% with RT plus placebo (HR 0.77, 95% CI 0.59–0.99). The 2025 long-term analysis reported 18-year OS of 53% versus 43% (adjusted HR 0.82, 95% CI 0.67–1.00; one-sided P=.025). At 18 years, prostate-cancer death was 18% versus 28%, and metastatic disease incidence was 22% versus 31%, respectively.
The secondary analysis by presalvage PSA is important: the net benefit of two years of high-dose bicalutamide was not uniform at very low PSA, and toxicity—especially gynecomastia—must be considered. Do not apply the average trial result indiscriminately to every contemporary early-salvage patient.
Current-practice context · reviewed 14 October 2026
RTOG 9601 established that adding long-term antiandrogen therapy can improve outcomes in a higher-risk salvage-RT population, but its regimen (bicalutamide 150 mg daily for 24 months) is not interchangeable with every modern ADT strategy. Today, timing of salvage RT, PSA at treatment, pathological risk, genomic/clinical risk and the choice and duration of ADT should be individualized; the low-PSA subgroup analysis cautions against automatic long-term hormonal therapy at very low PSA.