Could PSA Screening Predict Lethal Prostate Cancer Later in Life?

Higher than average prostate-specific antigen (PSA) levels in middle age may be predictive of a higher risk of lethal prostate cancer later in life, according to the results of a study published in the Journal of Clinical Oncology.

In a prospective study of men in the United States, researchers at the Harvard T.H. Chan School of Public Health and the Brigham and Women’s Hospital in Boston found that baseline PSA levels in men between the ages of 40 and 59 were associated with the risk of lethal prostate cancer years later.

Because of the potential for overdiagnosis and overtreatment, questions remain about how best to utilize PSA-based prostate cancer screening. Lorelei Mucci, MPH, ScD, associate professor of epidemiology at the Harvard T.H. Chan School of Public Health, and colleagues suggest that based on this study, PSA levels in middle-aged men may be used to risk-stratify patients to different prostate cancer screening schedules, including more intensive PSA screening for those with higher PSA levels.

The researchers analyzed data of male physicians between the ages of 40 and 59 who took part in the randomized Physicians’ Health Study, which began in 1982. The cohort was followed for 30 years and baseline PSA levels were available for 234 patients diagnosed with prostate cancer as well as for 711 age-matched control individuals. A total of 71 men developed lethal prostate cancer.

A total of 82%, 71%, and 86% of lethal prostate cancer cases occurred in men who had a PSA above the median at ages 40 to 49 (0.68 ng/mL), 50 to 54 (0.88 ng/mL), and 55 to 59 years (0.96 ng/mL), respectively. The cumulative incidence of lethal prostate cancer in men between 55 and 59 with a PSA below the median was 0.59% at 30 years.

The study authors suggest that as white men with a baseline PSA level below 1.0 ng/mL at age 60 were not likely to be diagnosed with lethal prostate cancer later in life, this group could possibly forgo further PSA screening.

“These findings do not necessarily imply that prostate biopsy or definitive treatment is immediately required in younger men with higher PSA levels at baseline, because this could lead to overdiagnosis, but only that they undergo more intensive PSA screening to enable earlier identification of cancer and potential cure while still possible,” wrote the authors in their discussion.

Limitations of the study include a limited number of lethal prostate cancer events, the potential that some of the men in the study received PSA screening prior to participating in the trial, and that the study population was made up predominantly of white men.