Comparison of Intermittent and Continuous Androgen Deprivation Therapy in Prostate Cancer Patients: An Up-to-Date Meta-analysis for Urologists and Medical Providers

Abstract

Introduction: Androgen deprivation therapy first became the treatment of choice for advanced prostate cancer in the 1940s with Charles Huggins' discoveries. Eight decades later, androgen deprivation therapy has significantly evolved, and yet is still utilized in various ways to treat certain forms of prostate cancer. For local recurrence after failed primary treatment and for locally advanced and metastatic disease, continuous androgen deprivation therapy has been standard of treatment. However, intermittent androgen deprivation therapy has emerged as a therapeutic alternative to continuous androgen deprivation therapy. The purpose of this meta-analysis is to provide an update on mortality, specifically prostate cancerespecific and nonprostate cancer causes, in order to offer some guidance when selecting the appropriate form of systemic androgen deprivation therapy. Methods:The PubMed database was searched for prospective randomized clinical trials. Inclusion and exclusion criteria were defined. Using statistical software, we analyzed random-effects models with the assumption that the data were randomly sampled, estimated the pooled log risk ratio, assessed heterogeneity, and created funnel plots to evaluate publication bias.Results: A total of 12 randomized clinical trials met all inclusion criteria for final analysis. There was no statistically significant difference in prostate cancerespecific mortality between intermittent androgen deprivation therapy and continuous androgen deprivation therapy ). The analysis of nonprostate cancer mortality favored intermittent androgen deprivation therapy over continuous androgen deprivation therapy, but the difference was statistically insignificant (RR¼0.94 [0.76-1.17]).Conclusions: These 2 treatment modalities can be considered as equivalent in long-term treatment outcomes. As intermittent androgen deprivation therapy is more cost-efficient and less likely to yield adverse side effects, future treatment guidelines should consider these advantages over continuous androgen deprivation therapy.

EORTC 2238 “De-Escalate”: a pragmatic trial to revisit intermittent androgen deprivation therapy in the era of new androgen receptor pathway inhibitors

“…Given that neither strategy showed superiority for time-to-event outcomes and iADT was associated with reduced cost, better convenience, and less potential toxicity, they recommended that men with relapsing locally advanced, or metastatic prostate cancer who achieved a good initial response to ADT be treated intermittently rather than continuously. Becker et al recently performed a meta-analysis of 12 randomized clinical trials using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines (19). There was no statistically significant difference in prostate cancer specific mortality between intermittent androgen deprivation therapy and continuous androgen deprivation therapy (RR=1.10 [0.85-1.42]) in this mixed population, comprising patients with failure after local treatment and locally advanced or metastatic prostate cancer.…”

“…Becker et al. recently performed a meta-analysis of 12 randomized clinical trials using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines ( 19 ). There was no statistically significant difference in prostate cancer specific mortality between intermittent androgen deprivation therapy and continuous androgen deprivation therapy (RR=1.10 [0.85-1.42]) in this mixed population, comprising patients with failure after local treatment and locally advanced or metastatic prostate cancer.…”