Lethal prostate cancer (PCa) is more likely to develop in men with a prostate-specific antigen (PSA) level above the median in midlife, according to a new study.

Using data from the Physicians’ Health Study, Mark A. Preston, MD, MPH, of Brigham and Women’s Hospital in Boston, and colleagues performed a case-control analysis of 234 mostly white men diagnosed with PCa and 711 controls aged 40 to 59 at baseline. Then, 71 men with lethal PCa (including cases of metastatic PCa) were re-matched to 213 controls for further analysis. 

Median PSA among age-matched controls was 0.68, 0.88, and 0.96 ng/mL for men aged 40 to 49, 50 to 54, and 55 to 59 years, respectively, according to results in the Journal of Clinical Oncology, published online ahead of print. Over 30 years of follow-up, the investigators found that the risk of lethal PCa was strongly associated with baseline PSA in midlife. Odds of lethal PCa increased by 8.7 at 40 to 49 years, 12.6 at 50 to 54 years, and 6.9 at 55 to 59 years, for men with a PSA value above the 90th percentile compared with at or below the median. Among all cases of lethal PCa, 82%, 71%, and 86% occurred in men with PSA levels above the median at ages 40 to 49, 50 to 54, and 55 to 59 years, respectively.

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A PSA measurement during middle age may be less confounded by benign prostatic hyperplasia, according to background information in the study. “We found a single baseline PSA-level measurement during midlife could accurately predict future risk of lethal prostate cancer,” Dr Preston stated in a press release. “These data identify subgroups of men, based on their PSA levels at a given age, who could benefit from screening intervals tailored to their actual magnitude of risk.”

The ideal screening interval based on midlife PSA level is unknown at this point. Men in the study had opportunistic PSA screening. “Our study does not imply prostate biopsy or definitive treatment is immediately required in younger men with higher PSA levels at baseline, as this could lead to over diagnosis…” the investigators stated.

The findings corroborate a study of unscreened Swedish men from the MalmÖ Preventive Project by Andrew J. Vickers, MD, and colleagues. The researchers found baseline PSA at age 40 to 55 predicted future PCa mortality (BMJ 346:f2023,2013). 

Men with PSA values below the median at 60 years old (below 1.0 ng/mL) are unlikely to develop lethal PCa, Dr Preston and colleagues further determined. As the Physicians’ Health Study included mostly white men, Dr Preston and his team are investigating this study question in African American men at higher risk of developing and dying from prostate cancer.

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1. Preston MA, Batista JL, Wilson KM, et al.  Baseline Prostate-Specific Antigen Levels in Midlife Predict Lethal Prostate Cancer. JCO [Epub ahead of print] doi:10.1200/JCO.2016.66.7527JCO.

2. Screening strategy may predict lethal prostate cancer later in life [press release]. Brigham and Women’s Hospital; June 13, 2016.