Analysis of trends in prostate-specific antigen (PSA) dynamics suggested that PSA growth rates, as well as the amount of PSA-level increase due specifically to cancer, might offer a means of distinguishing aggressive, potentially fatal prostate cancer from clinically inconsequential tumors, according to a study reported at the American Urological Association meeting.
Most deadly prostate cancers seem to produce smooth, fast, exponential PSA growth above a no-cancer baseline, said Thomas A. Neville, PhD, CEO of Soar Biodynamics in Incline Village, Nevada. At any PSA level, he added, the growth rate of the proportion of PSA from cancer predicted the aggressiveness and mortality risk associated with the disease.
Neville’s formula addresses the recommendation by the US Preventive Services Task Force (USPSTF) against screening for prostate cancer until tests more specific and reliable than PSA alone are available to identify deadly disease, he said. The new strategy also will aid men in making decisions about whether to screen by providing personalized risk information, another tenet called for by the USPSTF, he said.
“The predictive power, at similar PSA levels, of dynamic analysis of PSA trends helps identify deadly cancers prior to biopsy and may justify screening,” Neville said. “The earlier we can identify these cancers, the more lives we can save.”
Validation of the computational method was possible because researchers were granted access to “big data” in the form of 33 million PSA test results for 14 million men in the Veterans Affairs Health System, Neville said. The analysis involved 58,523 men ages 50 to 75 who were diagnosed with prostate cancer between 2001 and 2012. Each man had at least three PSA tests performed over 2 years prior to diagnosis.
Investigators employed analytic methods—fitting an exponential plus constant trend to the PSA tests for each man—to estimate the proportion of PSA concentration attributable to the cancer and to calculate the exponential growth rate of the cancer-derived PSA over time.
They found that men 50 to 75 years of age with a cancer-specific PSA of 3 to 7 who experienced a PSA growth rate of 15% to 30% over a no-cancer baseline faced a prostate cancer mortality of about 5% at 9 years. The 9-year mortality for that group increased with the PSA growth rate, exceeding 20% for men whose PSA growth rate was 100% or more.
Higher levels of cancer-specific PSA led to even larger differences in life expectancy. Nine years after diagnosis, men with cancer-related PSAs of 39 or greater faced an 85% risk of death, Neville said.
“The idea of screening that we’re moving toward is watching for trends to catch the cancer early, detect it effectively, and then treat it and try to save the patient’s life,” Neville said.
“For men with a PSA history, the growth rate calculated using these methods is highly indicative of which men harbor life-threatening prostate cancer,” he added. “This result may help address the challenge issued by the US Preventive Services Task Force to develop screening methods to distinguish potentially deadly cancers from nonprogressive or slowly progressive disease.”
Rawson L, MacKintosh R, Morrell C, et al. New analysis of PSA trends helps identify deadly cancers prior to biopsy. Presented at: the Annual Meeting of the American Urological Association; May 16-21, 2014; Orlando, Florida. Abstract MP63-04.