Intermittent Androgen Deprivation Therapy for Metastatic Prostate Cancer?

A randomized study failed to show that intermittent therapy was noninferior to continuous therapy with respect to survival.

Androgen deprivation therapy (ADT) for initial management of patients with metastatic prostate cancer has been the standard of care for more than 70 years. The dramatic rise in patients diagnosed with prostate cancer, following the advent of prostate-specific antigen (PSA) testing in the late 1980s, increased the ranks of those who underwent prostate surgery and radiotherapy and those who were ultimately found to have biochemical PSA failure. Many patients subsequently received ADT, often in the nonmetastatic setting, and were exposed to prolonged testosterone suppression, which unmasked such issues as increased risks for osteoporosis and metabolic syndrome. Thus, the intermittent use of ADT, to allow recovery of sexual function and to decrease other side effects such as hot flashes and weight gain, became a popular, albeit non-data-driven strategy.

Now, investigators from multiple U.S. cooperative groups have conducted a randomized trial involving 3040 patients with hormone-sensitive metastatic prostate cancer to test whether intermittent therapy is noninferior to continuous therapy with respect to survival and whether quality of life differed between patients assigned to either treatment 3 months after randomization. All patients received a luteinizing hormone–releasing hormone analogue and an antiandrogen agent for 7 months. Patients whose PSA level fell to 4 ng/mL were randomized to continuous ADT (765 patients) or intermittent ADT (770 patients). Patients were stratified according to a several factors, including performance status, prior hormone therapy, and extent of the disease. For those randomized to intermittent therapy, ADT was resumed when the PSA level rose to 20 ng/mL or sooner in patients who developed symptoms.

Median survival was 3.7 years for all patients after initiation of ADT and 1.7 years for patients whose PSA did not fall below 4 ng/mL and who were not randomized. Compared with continuous therapy, intermittent therapy was associated with better erectile function and mental health at 3 months, but not thereafter. At median follow-up of 9.8 years, median survival was 5.1 years in the intermittent-therapy group and 5.8 years in the continuous-therapy group (hazard ratio for death, 1.10; 90% confidence interval, 0.99 to 1.23).

CITATION(S):

Hussain M et al. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med 2013 Apr 4; 368:1314.