Overall survival is not meaningfully prolonged for patients with biochemically recurrent (BCR) prostate cancer who receive continuous androgen deprivation therapy (ADT) at the time of PSA relapse rather than metastasis, investigators suggest. They question early initiation of continuous ADT in these patients.

Catherine Handy Marshall, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues studied 806 high-risk patients (mean age 61 years; 16% Black) from Johns Hopkins Hospital and Walter Reed National Military Medical Center who experienced BCR after radical prostatectomy and delayed ADT initiation until metastasis. Median metastasis-free survival (MFS) was 144 months and 192 months from the time of local treatment in men with a PSA doubling time of less than 6 months and less than 10 months, respectively, the investigators reported in The Journal of Urology. Median overall survival (OS) from the time of local treatment was 168 and 204 months, respectively. Older age, higher pathologic T stage, higher Gleason sum, and faster PSA doubling time were all associated with higher likelihood of death.

Dr Marshall’s team compared their results with MFS and OS times from pivotal trials of high-risk patients with nonmetastatic castration-resistant prostate cancer who were treated with surgery, radiation, or primary ADT alone. Estimated median MFS was 136 vs 110 months in the apalutamide and placebo arms, respectively, of the SPARTAN trial, and 127 vs 103 months in the darolutamide and placebo arms, respectively, of the ARAMIS trial. Estimated median OS was 169 vs 154 months in the apalutamide and placebo arms, respectively, of the SPARTAN trial and not reached in the ARAMIS trial. OS times from these trials are comparable to those from the current study.

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“Men with biochemically recurrent prostate cancer, who defer hormone therapy until metastasis have overall survival that is quite long, and the early initiation of continuous androgen deprivation therapy for biochemical relapse may not meaningfully improve overall survival,” Dr Marshall’s team wrote. These data underscore the need to reevaluate when to start primary ADT in this patient population, the investigators highlighted.

In an accompanying editorial, David VanderWeele, MD, PhD, and Maha Hussain, MD, of the Robert H. Lurie Comprehensive Cancer Center at the Northwestern University Feinberg School of Medicine, in Chicago, Illinois, agreed that the risks of early ADT in men with biochemically recurrent prostate cancer may not outweigh the benefits:

“These data provide context for patients with BCR and providers on whether to undergo ADT for years despite unproven benefit and quality of life impact. New imaging may help or further add to the controversy, since BCR patients may have metastases on newer imaging. Until definitive data are available, men with BCR should be counselled regarding the lack of data to support ADT benefit in nonmetastatic BCR.”


Handy Marshall C, Chen Y, Kuo C, et al. Timing of androgen deprivation treatment for men with biochemical recurrent prostate cancer in the context of novel therapies. J Urol. 2021 Sep;206(3):623-629. doi:10.1097/JU.0000000000001797

VanderWeele D, Hussain M. Editorial comment. J Urol. 2021 Sep;206(3):629. doi:10.1097/JU.0000000000001797.01