Continuous androgen deprivation has been the standard therapy for metastatic hormone-sensitive prostate cancer. Despite a high response rate, resistance to androgen- deprivation therapy occurs in most patients, resulting in a median survival of 2.5 to 3 years. Replacing androgens before progression of the disease is hypothesised to prolong androgen dependence.
In this study, 3040 men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and PSA ≥5 ng/mL received a luteinising hormone–releasing hormone analogue and an antiandrogen agent for 7 months. Patients in whom the PSA level fell to ≤4 ng/mL were then randomised to continuous (n= 765) or intermittent (n= 770) androgen deprivation. The co-primary objectives were to assess whether intermittent therapy was non-inferior to continuous therapy with respect to survival (non-inferiority hazard ration threshold of 1.20) and whether quality of life differed between the groups 3 months after randomisation.
After a median follow-up period of 9.8 years, median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent- therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% CI, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (p<0.001 and p= 0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events.
The researchers conclude that these findings were statistically inconclusive in patients with metastatic hormone-sensitive prostate cancer, as the confidence interval for survival exceeded the upper boundary for non-inferiority, suggesting that a 20% greater risk of death with intermittent therapy than with continuous therapy, could not be ruled out, but too few events occurred to rule out significant inferiority of intermittent therapy. They suggest that these results may inform decision making about treatment for such patients.