Since the causative link between prostate cancer and androgen dependence was first highlighted in 1941, androgen deprivation has been the mainstay of treatment for men with metastatic prostate disease. Recently, the NCIC Clinical Trials Group convened a phase 3 trial with a primary end point of overall survival to investigate intermittent versus continuous androgen deprivation in men with rising PSA levels after radiotherapy and no evidence of metastatic disease.
This trial enrolled 1386 men, of whom 690 were randomly assigned to intermittent therapy and 696 to continuous therapy with a mean follow-up of 6.9 years. In the intermittent therapy group, 35% of men experienced full testosterone recovery, with potential benefits regarding physical function, fatigue, urinary problems, hot flashes, decreased libido, and erectile function. Median overall survival was 8.8 years and 9.1 years in the intermittent- and continuous-therapy groups, respectively (hazard ratio for death = 1.02).
Intermittent androgen deprivation was found to be non-inferior (nearly comparable) to continuous therapy with respect to overall survival in men with metastatic prostate cancer. The authors concluded that this trial raised several provocative issues in that the non-significant increase in deaths from other causes among patients in the continuous-therapy group could not be attributed to any specific non-toxic effects. However, the cost savings from reduction in drug use in the intermittent-therapy group could have been partially offset by the closer follow-up. While an intermittent approach to androgen deprivation does not necessarily yield inferior survival, some benefits in quality of life were observed.
Reference: Crook JM, O'Callaghan CJ, Duncan G, et al. Intermittent androgen suppression for rising PSA level after radiotherapy. NEJM 2012;367:895-903.