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Context: Androgen deprivation therapy (ADT) is the standard-of-care for men with metastatic hormone-sensitive prostate cancer (HSPC) and a potential treatment option in those with PSA relapse post local therapy. Based on promising biological and preclinical data several clinical trials compared the efficacy of intermittent (IAD) vs. continuous (CAD) with the objective of delaying disease progression and improving quality of life.Objective: The objective of this review is to revisit the concept of IAD in the "new world order" and reconsider if it has a potential clinical role in an era where we have seen unprecedented progress in the management of patients with metastatic HSPC. Evidence Acquisition: MEDLINE, Embase and the Cochrane Database were searched for randomized, controlled trials comparing IAD and CAD therapy. References of retrieved articles were also searched. Articles with at least 100 randomized patients that were published in 2008 or later and had data on overall survival or quality of life (QoL) outcomes were included. Evidence Synthesis: The evidence to date cannot exclude inferiority of IAD compared to CAD with respect to survival outcomes. The hazard ratios in metastatic disease indicate less favorable survival with IAD. No superiority trial conclusively favored IAD or CAD. Two trials demonstrated non-inferiority of IAD; though the non-inferiority margins are clinically concerning. Another trial could not exclude non-inferiority. A modest but temporary QoL and symptom benefit generally favoring IAD was observed.Conclusions: IAD has not conclusively demonstrated an impact on disease progression or survival and has only modest effects on QoL and symptoms measured in the short-term. As such, it is not standard-of-care, particularly in the era where we have seen unprecedented survival impact with combination ADT + docetaxel or abiraterone +prednisone. IAD may need to be reassessed in the context of current therapies, ideally driven by biological rationale, with the goal of minimizing physical and financial toxicities with appropriately designed informative clinical trials.

ObjectiveTo determine if a concurrent diagnosis of diabetes mellitus is associated with worse outcomes in advanced prostate cancer (PC). The effect diabetes may have on the progression of advanced PC is poorly understood.MethodsData on 148 advanced PC patients (35 with concurrent diabetes) were collected from an institutional database to obtain diabetic status, data on treatment types and durations, and prostate-specific antigen (PSA) values before, during, and after treatment. Time to castration resistance following the onset of androgen deprivation therapy (ADT) and overall survival (OS) in patients with and without diabetes were compared using univariate Cox regression analyses as the primary endpoints. Differences in PSA response to treatments were compared using chi-squared tests as a secondary endpoint.ResultsWith a median follow-up of 29 months, time to castration resistance did not differ significantly between patients with and without diabetes who underwent ADT. However, in a subset of patients who received ADT without radiographic evidence of metastases (N = 47), those with diabetes progressed to castration-resistant disease more quickly than those without DM (hazard ratio for progression with diabetes = 4.58; 95% CI: 1.92–10.94; p = 0.0006). Also, a lower percentage of patients undergoing ADT with diabetes had PSA declines of at least 50% (p = 0.17) and reached a nadir PSA <0.2 ng/mL (p = 0.06). OS did not differ based on diabetic status. No differences were seen in response to first-line therapy for castration-resistant prostate cancer.ConclusionDiabetes mellitus may have a detrimental effect on progression of advanced PC, particularly in those patients without radiographic evidence of metastases. Further study is necessary to fully elucidate the effect of diabetes on PC outcomes.

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