Salvage Radiotherapy for Prostate Cancer: The Role of Androgen Deprivation Therapy

Following radical prostatectomy, 20% to 50% of men experience a detectable prostate-specific antigen (PSA) level, frequently referred to as biochemical recurrence. Prostate bed radiotherapy (PBRT) administered in either the adjuvant or “salvage” setting has variably been shown to improve disease control rates, with recent data suggesting improved outcomes with early salvage therapy.

Investigators conducted an international phase 3 trial to test the role of adding androgen deprivation therapy (ADT) to PBRT alone or with pelvic lymph node radiotherapy (PLNRT). Over a 7-year period, 1792 patients with PSA values between 0.1 and 2.0 ng/mL after radical prostatectomy were randomized to receive PBRT alone, PBRT plus 4 to 6 months of ADT, or PBRT plus PLNRT plus ADT. The primary endpoint was freedom from progression (defined as biochemical progression using the Phoenix definition, clinical failure, or death from any cause).

Patients' median age was 64, 12% were Black, 16% had Gleason scores of 8 or 9, and 15% had pathologic seminal vesicle involvement. At the third interim analysis, with a minimum follow-up of 5 years, the 5-year freedom from progression rate was 71.1% in patients receiving PBRT alone versus 89.1% in those receiving PBRT/PLNRT plus ADT (difference, 17·9%; standard error, 2·9%; P<0.0001), In the final analysis, with a median follow-up of 8.2 years, 5-year freedom from progression rates were 70.9% and 87.4% in those two treatment groups, respectively. In the PBRT plus ADT group the freedom from progression rate was 81.3%.

Late grade 3 or worse toxicity was similar in all treatment groups, although there were more late grade 2 blood and marrow events in the PBRT/PLNRT plus ADT arm than in the PBRT plus ADT arm.