Background
Phase III double-blind, placebo-controlled RCT (RTOG 9601). 760 men with pT2 (positive margin) or pT3 pN0 prostate cancer after radical prostatectomy with detectable PSA 0.2–4.0 ng/mL. Enrolled 1998–2003. Median follow-up 13 years.
Interventions and follow up
Arm A: Salvage radiotherapy (64.8 Gy) + bicalutamide 150 mg/day × 24 month
Arm B: Salvage radiotherapy (64.8 Gy) + placebo × 24 month
Primary endpoint: Overall survival
mFollow up: 13 year
Arm B: Salvage radiotherapy (64.8 Gy) + placebo × 24 month
Primary endpoint: Overall survival
mFollow up: 13 year
Results
OS at 12 years: 76.3% (bicalutamide) vs 71.3% (placebo), HR 0.77 (95% CI 0.59–0.99), P=.04
Death from prostate cancer at 12 years: 5.8% vs 13.4%, P<.001
Metastatic prostate cancer at 12 years: 14.5% vs 23.0%, P=.005
Death from prostate cancer at 12 years: 5.8% vs 13.4%, P<.001
Metastatic prostate cancer at 12 years: 14.5% vs 23.0%, P=.005
Adverse events
Main adverse events: Gynecomastia: 69.7% (bicalutamide) vs 10.9% (placebo), P<.001. Late radiation toxicity similar between groups. No significant difference in grade ≥3 non-gynecological adverse events.
Conclusions
Addition of 24 months of bicalutamide to salvage radiotherapy significantly improved long-term overall survival and reduced prostate cancer-specific mortality and metastasis compared with salvage RT alone. This established concurrent and adjuvant antiandrogen therapy as a standard option in post-prostatectomy salvage RT.
Key Limitations
Key Limitations: High-dose bicalutamide (150 mg/day) is not standard of care in most countries (not FDA-approved for this indication at this dose). Very high rate of gynecomastia limits tolerability. Contemporary salvage RT trials use LHRH agonists (goserelin), not bicalutamide. PSA eligibility threshold (0.2–4.0 ng/mL) is broader than currently recommended; subset analyses suggest OS benefit primarily in PSA >0.7 ng/mL, raising concern about overtreatment in low-PSA patients.
Clinical Context
RTOG 9601 provided the first OS benefit evidence for adding hormonal therapy to salvage RT, catalyzing subsequent trials (GETUG-AFU 16, SPPORT). Current practice incorporates short-course LHRH agonists rather than bicalutamide. SPPORT showed further benefit from pelvic nodal irradiation in higher-risk patients.
References
References: Shipley WU et al, NEJM 2017; PMID: 28146658