News Release

Falling PSA levels predict longer survival in prostate cancer patients at high risk of metastases

Peer-Reviewed Publication

Wolters Kluwer Health

February 10, 2023 – Declines in prostate-specific antigen (PSA) level after treatment with the next-generation androgen receptor inhibitor drug enzalutamide predict improved survival rates in men with non-metastatic castration-resistant prostate cancer (nmCRPC), reports The Journal of Urology®, an Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Our analysis of data from the PROSPER study shows a previously unappreciated relationship between changes in PSA levels and clinical outcomes in men with nmCRPC," comments lead author Maha Hussain, MD, of Northwestern University Feinberg School of Medicine, Chicago. "The findings may help us to make personalized decisions regarding clinical follow-up and imaging studies for a group of patients at high risk of prostate cancer metastases."

PROSPER trial data used to explore enzalutamide's effects on PSA levels

The researchers analyzed data from the PROSPER trial, published in 2018, which enrolled men with nmCRPC and rapidly rising PSA levels. Increases in PSA signal an increased risk that the cancer will spread, or metastasize, outside of the prostate gland. In patients with nmCRPC, rising PSA levels are often the first sign that the cancer is growing. (The Urology Care Foundation has more information on nmCRPC.)

The 'castration-resistant' part of nmCRPC means that the cancer no longer responds to standard hormone therapy. The PROSPER trial was designed to evaluate the effects of enzalutamide – a novel hormonal agent that works by directly blocking the androgen receptor to block androgen's effects in the promotion of prostate cancer growth. The initial PROSPER results showed longer survival times in men who received enzalutamide added to androgen deprivation therapy.

Dr. Hussain and colleagues used 12-month follow-up data from the PROSPER study to assess how PSA levels responded to enzalutamide. Changes in PSA levels and patient survival rates were compared for 905 patients treated with enzalutamide and 457 treated with placebo.

Most patients had sharp reductions in PSA after enzalutamide treatment. More than 97% of men in the enzalutamide group had at least a 50% decrease in PSA. In 38% of patients, PSA levels decreased by at least 90%.

Greater declines in PSA linked to lower risk of metastases, longer survival

The reduction in PSA levels with enzalutamide treatment was a strong predictor of eventual survival rates, the analysis showed. Median metastasis-free survival – reflecting how long the men survived without cancer spread – was 37 months in patients with a PSA decline of 90% or greater, compared to about 22 months in those whose PSA level decreased by less than  50%.

Overall survival time was also related to enzalutamide response, ranging from 41 months with less than a 50% decline in PSA to 54 months with a 90% decline or greater. For men who had a 90% decline or greater and a PSA nadir (low point) of 0.2 ng/mL or less, survival time increased to 64 months, with the median survival time "not reached" – meaning that longer follow-up would be needed to show the final overall survival benefit.

The researchers believe their findings have implications not only for the predicting the outcomes of enzalutamide therapy but also for personalized treatment of nmCRPC. The study "further underscores the value of PSA as an intermediate biomarker for treatment benefit and risk of disease progression in patients with nmCRPC," Dr. Hussain and coauthors write. They call for further studies to clarify the dynamics of changes in PSA levels in response to enzalutamide, including the significance of reaching a PSA nadir of 0.2 ng/mL or less.

Read [Nadir Prostate-specific Antigen as an Independent Predictor of Survival Outcomes: A Post Hoc Analysis of the PROSPER Randomized Clinical Trial]

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About The Journal of Urology®

The Official Journal of the American Urological Association (AUA), and the most widely read and highly cited journal in the field, The Journal of Urology® brings solid coverage of the clinically relevant content needed to stay at the forefront of the dynamic field of urology. This premier journal presents investigative studies on critical areas of research and practice, survey articles providing brief editorial comments on the best and most important urology literature worldwide and practice-oriented reports on significant clinical observations. The Journal of Urology® covers the wide scope of urology, including pediatric urology, urologic cancers, renal transplantation, male infertility, urinary tract stones, female urology and neurourology.

About the American Urological Association

Founded in 1902 and headquartered near Baltimore, Maryland, the American Urological Association is a leading advocate for the specialty of urology, and has more than 23,000 members throughout the world. The AUA is a premier urologic association, providing invaluable support to the urologic community as it pursues its mission of fostering the highest standards of urologic care through education, research and the formulation of health care policy. To learn more about the AUA visit:

About Wolters Kluwer

Wolters Kluwer (WKL) is a global leader in professional information, software solutions, and services for the healthcare; tax and accounting; governance, risk and compliance; and legal and regulatory sectors. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with specialized technology and services.

Wolters Kluwer reported 2021 annual revenues of €4.8 billion. The group serves customers in over 180 countries, maintains operations in over 40 countries, and employs approximately 20,000 people worldwide. The company is headquartered in Alphen aan den Rijn, the Netherlands.

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