Anti-Androgen Therapy Overcomes the Time Delay in Initiation of Salvage Radiation Therapy and Rescues the Oncological Outcomes in Men with Recurrent Prostate Cancer After Radical Prostatectomy: A Post Hoc Analysis of the RTOG-9601 Trial Data.

Late salvage radiation therapy (sRT) was associated with significantly worse overall mortality compared to early sRT, but this difference was eliminated with the addition of anti-androgen therapy (AAT).

• At 15 years, overall mortality rates were 22.9% (early sRT), 22.8% (early sRT with AAT), 40.1% (late sRT), and 22.9% (late sRT with AAT); log-rank p = 0.0039
• Time-varying multivariable analysis showed increased hazard of overall mortality for late sRT versus early sRT (HR 1.49, 95% CI 1.02–2.17)
• After addition of concomitant AAT to late sRT, no difference in overall mortality remained compared to early sRT (HR 0.85, 95% CI 0.55–1.32)
• Median follow-up was 14.7 years with 670 men from the RTOG-9601 trial

Cancer-specific mortality was significantly higher with late sRT compared to early sRT, but the addition of AAT to late sRT negated this difference.

• At 15 years, CaP-specific mortality rates were 12.1% (early sRT), 3.9% (early sRT with AAT), 22.7% (late sRT), and 8.0% (late sRT with AAT); Gray's p = 0.0004
• Time-varying multivariable adjusted analysis showed worse hazards of cancer-specific mortality for late sRT versus early sRT
• Hazards of cancer-specific mortality were no different after addition of AAT to late sRT compared to early sRT

Metastatic progression was significantly worse with late sRT compared to early sRT, but this difference was eliminated when AAT was added to late sRT.

• At 15 years, metastasis rates were 18.8% (early sRT), 14.6% (early sRT with AAT), 35.9% (late sRT), and 19.5% (late sRT with AAT); Gray's p = 0.0004
• Time-varying multivariable adjusted analysis demonstrated worse hazards of metastatic progression for late sRT versus early sRT
• Hazards of metastatic progression were no different after addition of AAT to late sRT compared to early sRT

The study stratified patients into four treatment groups based on pre-sRT PSA levels and AAT use, using the cut-off reported in the original RTOG-9601 trial.

• Early sRT was defined as pre-sRT PSA < 0.7 ng/mL; late sRT was defined as pre-sRT PSA ≥ 0.7 ng/mL
• Data from 670 men who participated in the RTOG-9601 trial and experienced biochemical recurrence were extracted from the NCTN data archive platform
• Four groups analyzed: early sRT, early sRT with AAT, late sRT, and late sRT with AAT
• Statistical analyses used time-varying Cox proportional hazards and Fine-Gray competing-risk regression to assess adjusted hazards

The addition of AAT to early sRT produced the lowest cancer-specific mortality rate among all four groups at 15-year follow-up.

• CaP-specific mortality was 3.9% for the early sRT with AAT group, compared to 12.1% for early sRT alone, 22.7% for late sRT, and 8.0% for late sRT with AAT
• Metastasis rate was 14.6% for early sRT with AAT, the lowest among all groups
• Gray's p = 0.0004 for both CaP-specific mortality and metastasis comparisons across groups