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Men with prostate cancer and biochemical recurrence (BCR) who delayed androgen deprivation therapy (ADT) still experienced long survival outcomes, researchers reported.

In a retrospective study, men with a prostate-specific antigen doubling time (PSADT) of less than 10 months saw a median metastases-free survival (MFS) of 192 months when they delayed ADT until metastasis, and a median overall survival (OS) of 204 months, reported Catherine Handy Marshall, MD, of Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The results were comparable to outcomes from phase III trials of androgen receptor-targeted therapy in men with nonmetastatic castration resistant prostate cancer (nmCRPC), in the .

Thus, early initiation of ADT for BCR may not meaningfully improve OS, and the study "underscores the need to reevaluate when to start primary ADT in this patient population," they wrote.

The authors pointed out that while recent nmCRPC clinical trials -- SPARTAN, ARAMIS, and PROSPER -- indicated that the use of novel androgen receptor antagonists significantly improve MFS and OS in men with nmCRPC, "it should be emphasized that the nmCRPC clinical state results from a controversial practice of initiation of early ADT, which remains unsubstantiated by level 1 evidence."

The natural history of patients with BCR suggests that this is a widely heterogenous group of patients in terms of the natural progression of metastases and survival, the authors pointed out, and that the question of how to treat them remains controversial. They added that this question has particular relevance in the case of the early initiation of ADT, considering that these patients can survive for many years and that ADT is both costly and associated with significant side effects.

The authors reviewed data from 806 men with clinically localized prostate cancer who underwent radical prostatectomy at Johns Hopkins University and the Walter Reed National Military Medical Center in Bethesda, Maryland. These men developed BCR with a PSADT of less than 10 months, which the authors explained was consistent with the eligibility criteria of nmCRPC trials.

Median age of the cohort was 61 years, while 79% of the men were white and 16% were Black.

Marshall and colleagues found that the median MFS of men with BCR and a PSADT of less than 6 months was 144 months, with a median OS 0f 168 months.

They noted that the SPARTAN trial, a phase III study of apalutamide (Erleada) versus placebo in patients with nmCRPC, demonstrated an MFS from local treatment of 136 months in the apalutamide arm and 110 months in the placebo arm, and an estimated OS of 169 months and 154 months, respectively.

The ARAMIS trial evaluated darolutamide (Nubeqa) and demonstrated an MFS of 126.6 months in the study-drug arm and 102.6 months in the placebo arm, while OS was not reached. "Our results are in line with the estimated OS in the SPARTAN and ARAMIS trials," Marshall's group observed.

"Adequately designed prospectively randomized studies in patients with BCR testing the role of early vs deferred ADT remain critical to inform treatment decisions in this population and enhance patients' and physicians' understanding of the clinical significance of the nmCRPC pivotal studies," they wrote.

In an accompanying , David VanderWeele, MD, PhD, and Maha Hussain, MD, both of the Northwestern University Feinberg School of Medicine in Chicago, wrote that the study results "provide context for patients with BCR and providers on whether to undergo ADT for years despite unproven benefit and quality of life impact."

They agreed with the authors that more definitive data are needed on the question of early versus delayed ADT, and that until that time, men with BCR should be counseled on the lack of data supporting the benefit of ADT in nonmetastatic BCR.

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