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Cardiovascular risk in ADT recipients: does the type of ADT matter?

Prostate Cancer and Prostatic Diseases (2024)Cite this article

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Men with prostate cancer (PC) are at high risk for cardiovascular disease (CVD) [1]. The role of androgen-deprivation therapy (ADT) in promoting CVD remains uncertain. Observational evidence from large administrative databases associate ADT usage with the development of cardiovascular events (CVE), but findings are limited due to inherent bias associated with retrospective analyses, mainly the absence of key covariates in these databases [2]. We are awaiting the results of RADICAL-PC (NCT03127631) to determine the association between ADT and CVEs. Meanwhile, our analysis of the cardiovascular risk profile of the first 2492 consecutive Canadian men prospectively enrolled in RADICAL-PC demonstrates that there is a positive association between planned ADT and baseline cardiovascular risk factors, however, the risk is abolished after adjustment for confounders [3]. Therefore, observations linking ADT to CVD may, at least in part, be explained by the inherent high-risk cardiovascular profile of PC patients in need of ADT. Given the prolonged survivorship of PC patients, including those receiving ADT, minimizing cardiovascular morbidity is desirable. Can this be achieved by selecting an ADT modality with lower cardiotoxicity?

The debate about whether gonadotropin-releasing hormone (GnRH)-antagonists associate with a more favorable cardiovascular safety profile compared with GnRH-agonists is far from being settled. At the moment, there is no level I evidence to support or refute this hypothesis. The relatively low CVE rates in two recent randomized trials (PRONOUNCE, NCT02663908 [4] and REPLACE-CV, NCT05605964) designed to specifically test this hypothesis likely caused both to terminate prematurely. In the absence of randomized clinical trials, what do we know to support this hypothesis and what have we learnt thus far?

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Fig. 1: The different levels of evidence that weigh in the balance between GnRH-antagonists and GnRH-agonists and their cardiovascular risk profile in prostate cancer patients on ADT.

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Authors and Affiliations

  1. Department of Surgery, Division of Urology, Faculty of Medicine, McMaster University, Hamilton, ON, Canada

    Jehonathan H. Pinthus & Wilhelmina C. M. Duivenvoorden

  2. Research Institute of St. Joe’s Hamilton, Hamilton, ON, Canada

    Jehonathan H. Pinthus & Wilhelmina C. M. Duivenvoorden

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  1. Jehonathan H. Pinthus
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  2. Wilhelmina C. M. Duivenvoorden
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Contributions

JHP and WCMD: Conception, review of literature, critical revisions.

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Correspondence to Jehonathan H. Pinthus.

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Competing interests

JHP has acted in a consulting role for Ferring Pharmaceuticals, Sumitomo Pharma and Antev Ltd. and received research funding from Ferring Pharmaceuticals. WCMD has no conflict of interests.

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Pinthus, J.H., Duivenvoorden, W.C.M. Cardiovascular risk in ADT recipients: does the type of ADT matter?. Prostate Cancer Prostatic Dis (2024). https://doi.org/10.1038/s41391-024-00832-0

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