Background
Phase III randomized non-inferiority trial; 1386 men with rising PSA >3 ng/mL (testosterone >5 nmol/L) more than 12 months after definitive radiotherapy (primary or salvage). Tested whether intermittent ADT preserves survival versus continuous ADT.
Interventions and follow up
Arm A (continuous): Continuous LHRH agonist + non-steroidal antiandrogen (≥4 weeks) or orchiectomy.
Arm B (intermittent): 8-month cycles of LHRH agonist + non-steroidal antiandrogen; off-treatment if no progression and PSA <4 ng/mL, resumed when PSA >10 ng/mL.
Primary endpoint: Overall survival (non-inferiority).
mFollow up: 6.9 years.
Arm B (intermittent): 8-month cycles of LHRH agonist + non-steroidal antiandrogen; off-treatment if no progression and PSA <4 ng/mL, resumed when PSA >10 ng/mL.
Primary endpoint: Overall survival (non-inferiority).
mFollow up: 6.9 years.
Results
mOS: 8.8yr (intermittent) vs 9.1yr (continuous); HR 1.02, 95%CI 0.86–1.21, meeting non-inferiority.
Median ADT exposure: 15.4mo (intermittent) vs 43.9mo (continuous).
Quality of life: Intermittent therapy improved hot flashes, libido, and urinary symptoms during off-treatment intervals.
Median ADT exposure: 15.4mo (intermittent) vs 43.9mo (continuous).
Quality of life: Intermittent therapy improved hot flashes, libido, and urinary symptoms during off-treatment intervals.
Adverse events
Overall: Grade ≥4 events similar between arms (~11.5%).
Common (both arms): Hot flashes, gynecomastia, and fatigue were the predominant toxicities; reduced during off-treatment periods in the intermittent arm.
Common (both arms): Hot flashes, gynecomastia, and fatigue were the predominant toxicities; reduced during off-treatment periods in the intermittent arm.
Conclusions
In men with PSA relapse after radiotherapy, intermittent ADT was non-inferior to continuous ADT for overall survival and offered improved quality of life with less testosterone-suppression burden.
Key Limitations
Restricted to non-metastatic PSA-relapse after radiotherapy; findings do not extend to overt metastatic disease, where a separate intermittent-versus-continuous trial (SWOG 9346) could not exclude inferiority in low-volume metastases.
Clinical Context
Supports ASCO/ESMO acceptance of intermittent ADT as a reasonable option for biochemically relapsed non-metastatic prostate cancer to reduce androgen-deprivation morbidity.