Midlife PSA levels strongly portend future deadly PCa

PSA levels in midlife are strong predictors of future lethal prostate cancer among U.S. men, according to a recent study published online in the Journal of Clinical Oncology (July 13, 2016).

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Dr. Preston“It appears that baseline PSA is a lot more predictive than either family history or race alone and should be used to risk stratify screening,” study co-lead author Mark Preston, MD, MPH, of Brigham and Women’s Hospital, Boston, told Urology Times.

Dr. Preston and colleagues studied men ages 40 to 59 years who gave blood prior to participating in the Physicians’ Health Study. Baseline PSA levels were available for 234 prostate cancer patients and 711 age-matched controls. Seventy-one subjects developed lethal prostate cancer and were rematched to 213 controls, according to the study’s abstract. Using information from 234 men who were diagnosed with prostate cancer, the authors measured PSA levels from stored plasma samples and followed the men’s outcomes.

There are very few study populations available in any country that have access to baseline blood samples, excellent accounting of lethal prostate cancer outcomes, and the extensive follow-up required to investigate the question of whether a baseline PSA level during midlife predicts lethal prostate cancer in a U.S. population with opportunistic screening, according to Dr. Preston.

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“Furthermore, as this is a U.S. population subject to opportunistic PSA screening, it is generalizable to a contemporary population,” he said.

Next: What the authors found

They found the median PSA among controls was 0.68 ng/mL for men ages 40 to 49 years, 0.88 ng/mL among men ages 50 to 54 years, and 0.96 ng/mL for men ages 55 to 59 years. The risk of lethal prostate cancer was strongly associated with baseline PSA in midlife. Of the lethal prostate cancer events, 82% occurred in men with baseline PSAs above the median at ages 40 to 49 years, 71% in men 50 to 54 years, and 85% in those ages 55 to 59 years.

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“There was no lower PSA limit with which men never developed lethal prostate cancer, although it was exceptionally rare,” Dr. Preston said. “What this means is that one PSA measure in midlife (45 to 50 years of age) is not adequate to never screen men again. The exact interval is unclear but likely in the range of 5 to 10 years.”

Recent studies have shown a decrease in PSA testing over the last few years, according to an analysis published in JAMA(2015; 314:2054-61), Dr. Preston said.

“This is likely due to primary care physicians typically ordering [about] 90% of PSA screening tests and now following the USPSTF task force recommendations of not screening,” Dr. Preston said. “I think this is problematic and akin to ‘throwing the baby out with the bathwater.’ PSA is by no means perfect but definitely has value. We need smarter screening practices based on actual risk (baseline PSA level, family history, race) in order to identify cancers that will cause symptoms or death, in time to provide curative treatment, while avoiding over-diagnosis and subsequent over-treatment in those men unlikely to benefit due to elderly age or limited life expectancy.”

While men are still much more likely to die of something other than prostate cancer, there is an important benefit associated with smarter PSA screening practices, according to Dr. Preston.

“[That] would be in the ability to target those at higher risk of developing aggressive prostate cancer with regular screening while ‘letting be’ those men at low risk,” he said. “Men with a PSA below 1 ng/mL at age 60 (the median for 60-year-old men) have an incredibly low risk of developing lethal prostate cancer and likely don’t need further screening.”

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