TOPLINE

A real-world analysis suggests that achieving a prostate-specific antigen (PSA) level < 0.2 ng/mL within 9 months of starting androgen deprivation therapy (ADT)-based treatments was the PSA benchmark most consistently associated with improved overall survival in men with metastatic castration-sensitive prostate cancer. Achieving a PSA level < 0.2 ng/mL within 9 months of ADT initiation was associated with a significantly lower subsequent risk for death, while achieving 90% or greater PSA decline but not a PSA level < 0.2 ng/mL was not tied to improved overall survival.

METHODOLOGY

• Multiple phase 3 studies in men with metastatic castration‐sensitive prostate cancer indicate that a PSA nadir < 0.2 ng/mL is a preferred threshold for PSA response, but in real‐world practice, physicians often use other metrics, such as percentage of PSA decline, the authors explained.
• To better understand the optimal PSA threshold, researchers conducted a retrospective analysis of Veterans Health Administration (VHA) data from January 1, 2006, to August 31, 2024, which included 4890 patients with metastatic castration-sensitive prostate cancer who initiated ADT-based therapy.
• Patients were older than 18 years at index date and had documented secondary metastasis codes, evidence of castration sensitivity, and available PSA values at baseline (365 days before ADT initiation) and during follow-up while on initial treatment.
• PSA response metrics included more than 90% decline from baseline PSA and a PSA level < 0.2 ng/mL. Median follow-up was 25 months and median PSA follow-up during index treatment was 15 months, with most patients having 2-7 PSA measurements (overall median, 4) during the follow-up period.
• Primary outcomes included overall survival, defined as time from 9 months post–index date to death, and time to disease progression, defined as time from 9 months post–index date to PSA progression, initiation of new antineoplastic treatment, castration resistance, or death.

TAKEAWAY

• Achieving a PSA level < 0.2 ng/mL within 9 months of ADT initiation was associated with a 54% lower risk for death than not reaching that PSA threshold (adjusted hazard ratio [aHR], 0.46; P < .001).
• Overall survival improvements with a PSA level < 0.2 ng/mL were similar regardless of whether patients achieved more than 90% PSA decline (aHR, 0.43; P < .001) or less than 90% PSA decline (aHR, 0.36; P < .001).
• Achieving a 90% or greater PSA decline without reaching a PSA level < 0.2 ng/mL was not associated with significantly improved overall survival (HR, 0.88; P = .13) or improved disease progression (HR, 1.14; P = .086) compared with not achieving either target.
• Patients who initiated ADT plus androgen receptor pathway inhibitors vs ADT alone were more likely to achieve a PSA level < 0.2 ng/mL during PSA follow-up (aHR, 1.71; P < .001) and within 9 months of treatment initiation (odds ratio, 2.36; P < .001).

IN PRACTICE

In a real-world metastatic castration-sensitive prostate cancer setting, achieving a PSA level < 0.2 ng/mL within 9 months of initiating ADT-based treatments, whether or not a PSA decline of 90% was reached, was associated with improved overall survival, “which supports a PSA nadir of < 0.2 ng/mL for optimizing [metastatic castration-sensitive prostate cancer] outcomes,” the authors concluded.

SOURCE

The study, led by Stephen J. Freedland, MD, Department of Urology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, was published online in Cancer.

LIMITATIONS

As a retrospective cohort study of the VHA population, it is unclear whether findings are applicable beyond the VHA. The analyses did not adjust for confounding clinical parameters such as tumor grade and disease volume that were not available in the VHA dataset. A recorded prescription does not necessarily indicate that the patient took the treatment as prescribed. Patient-level variations in follow-up PSA assessment timepoints in real-world settings could affect the results of time-to-event analyses.

DISCLOSURES

This study was funded by Pfizer Inc. and Astellas Pharma Inc., the codevelopers of enzalutamide. Freedland disclosed having consulting or advisory roles with Astellas Pharma Inc.; AstraZeneca; Bayer; Candel; Eli Lilly; Johnson & Johnson Innovative Medicine (formerly Janssen); Merck; Novartis; Pfizer Inc.; Sanofi; Sumitomo Pharma America, Inc. (formerly Myovant Sciences); and Tolmar. Wei Gao, Hongbo Yang, Jingyi Chen, and Grace Chen reported being employees of Analysis Group, which received consulting fees from Pfizer Inc. David Russell and Jasmina I. Ivanova reported being employees and shareholders in Pfizer Inc. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.