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JU INSIGHT: Nadir Prostate-specific Antigen as a Predictor of Survival Outcomes: The PROSPER Trial

By: Maha Hussain, MD, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cora N. Sternberg, MD, Englander Institute for Precision Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, New York; Eleni Efstathiou, MD, PhD, MD Anderson Cancer Center, Houston, Texas; Karim Fizazi, MD, PhD, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France; Qi Shen, MD, PhD, Pfizer Inc., Collegeville, Pennsylvania; Xun Lin, PhD, Pfizer Inc., La Jolla, California; Jennifer Sugg, MS, Astellas Pharma, Inc., Northbrook, Illinois; Joyce Steinberg, MD, Astellas Pharma, Inc., Northbrook, Illinois; Bettina Noerby, MD, PhD, Sygehus, Lillebaelt, Vejle, Denmark; Ugo De Giorgi, MD, PhD, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy; Neal D. Shore, MD, Carolina Urologic Research Center, GenesisCare US, Myrtle Beach, South Carolina; Fred Saad, MD, University of Montreal Hospital Center, Canada | Posted on: 17 Mar 2023

Hussain M, Sternberg CN, Efstathiou E, et al. Nadir prostate-specific antigen as an independent predictor of survival outcomes: a post hoc analysis of the PROSPER randomized clinical trial. J Urol. 2023;209(3):532-539.

Study Need and Importance

PSA monitoring is an important indicator of treatment response and progression following definitive therapy. Although PSA has been investigated in men with nonmetastatic castration-resistant prostate cancer (nmCRPC), the relationship between PSA decline, nadir PSA during treatment, and survival outcomes has not been fully elucidated.

What We Found

In enzalutamide-treated men, PSA declines of <50%, ≥50% to <90%, ≥90% with nadir ≥0.2 ng/mL, and ≥90% with nadir <0.2 ng/mL were associated with median metastasis-free survival in months of 22.1, 34.2, 36.6, and not reached, respectively, and overall survival in months of 40.8, 54.4, 64.3, and not reached, respectively. In other words, PSA declines of ≥50% to <90%, ≥90% with nadir ≥0.2 ng/mL, and ≥90% with nadir <0.2 ng/mL were associated with 62% (P = .003), 78%, and 90% (both P < .001) reduced risk of metastasis, respectively, and with 57%, 75%, and 89% (all P < .001) reduced risk of death, respectively, vs <50% decline (see Figure).

Figure. Visual abstract of study.


Study limitations included that the analyses were not prespecified in the protocol or post hoc, and thus the results should be considered exploratory and interpreted with caution. Additionally, the ability of next-generation imaging to detect metastases below the limit of detection for PSA may redefine the current definitions of nmCRPC and metastasis-free survival.

Interpretation for Patient Care

The relationship between PSA dynamics (eg, absolute and percent change) and survival outcomes suggests a potential to guide monitoring and treatment decisions, manage expectations of treatment efficacy, and serve as a prognostic tool in nmCRPC. It is important to note not only the prognostic value of these findings, but also the value for clinicians in personalizing intensity of follow-up, imaging, clinical trial referral, and intervention for those with poor therapeutic response. Men with lesser PSA declines should warrant closer monitoring including radiographic studies.