Intermittent versus continuous androgen deprivation therapy for advanced prostate cancer

Abstract

Androgen deprivation therapy (ADT) is still a mainstay of treatment for advanced prostate cancer. Continuous ADT causes considerable patient morbidity including sexual dysfunction, poor mood and physical capacity, changes in body composition and health-care-related costs. Intermittent ADT has been used as an approach to ADT monotherapy to limit morbidity by enabling cyclical recovery of serum testosterone levels. To date, a number of well-performed randomized controlled trials and meta-analyses have demonstrated statistically insignificant differences in oncological outcomes between intermittent and continuous ADT monotherapy. Sexual outcomes, morbidity profiles and cost-savings favour intermittent therapy in most randomized trials, but the benefit for clinical practice is unclear. Despite the growing body of evidence, the optimal administration regime for ADT has not been clearly established and incorporation of adjunctive upfront treatments such as chemotherapy and novel anti-androgen agents has further hampered progress. Recommendations by authoritative urological and oncological societies regarding the use of intermittent ADT are limited. The potential benefits of reduced morbidity for a particular patient must be considered in light of the possible oncological outcomes. Although the oncological changes associated with intermittent ADT are controversial, intermittent ADT does seem to provide symptomatic benefit in patients compared with continuous ADT. However, careful selection of suitable patients is crucial.

Key points

  • Intermittent androgen deprivation therapy (ADT) has been proposed to reduce the adverse events and poor quality of life associated with continuous ADT.

  • Current data do not show that intermittent ADT is inferior to continuous ADT with statistical certainty.

  • Quality-of-life measures (including mental health, physical capacity and sexual health) favour intermittent ADT compared with continuous ADT.

  • In the current era of early systemic therapy for hormone-sensitive disease, intermittent ADT is likely to be best suited to patients with M0 or low-volume M1 disease.

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Fig. 1: Administration regimes for intermittent ADT.
Fig. 2: Suggested algorithm for identifying patients with advanced prostate cancer who are suitable for either intermittent or continuous ADT.

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M.P., N.P. and S.S. researched data for the article, M.P., L.K. and C.S.H. made substantial contributions to discussions of content, M.P., M.J.R., D.B., and N.L. wrote the article and L.K., C.S.H., N.P., S.S., D.B. and N.L. reviewed and edited the manuscript before submission.

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Correspondence to Marlon Perera.

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Perera, M., Roberts, M.J., Klotz, L. et al. Intermittent versus continuous androgen deprivation therapy for advanced prostate cancer. Nat Rev Urol 17, 469–481 (2020). https://doi.org/10.1038/s41585-020-0335-7

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