Although a government-funded panel says that healthy men should not have prostate-specific antigen testing to assess the likelihood that they have prostate cancer, no other screening tests are set to replace it.
With a national panel advising against routine PSA testing, how close are other screening tests to supplementing or replacing it?
In May, the government-funded U.S. Preventive Services Task Force (USPSTF) recommended that healthy men of all ages skip routine prostate cancer screening, saying that the harm caused by the prostate-specific antigen (PSA) blood test outweighs any benefit.
In its recommendation, the panel acknowledged that a large ongoing randomized trial of PSA screening in Europe found a “very small” reduction in prostate cancer mortality—about 1 death per 1,000 men over about 10 to 14 years. However, an American study showed no reduction, and the panel noted that screening often generates false-positive results that necessitate additional testing, including biopsies, because PSA is not prostate-cancer specific. (The panel didn't address false negatives, but about 15% of men with a “normal” PSA level actually do have prostate cancer.)
Once diagnosed with prostate cancer, nearly 90% of men in the United States undergo treatment even though the disease typically progresses so slowly that it's unlikely ever to cause symptoms during their lifetime. Treatment can cause a variety of side effects, including urinary incontinence, erectile dysfunction, and bowel problems. In addition, about 5 of every 1,000 men who undergo surgery will die within a month of the procedure, the report says.
Researchers have sought to overcome the challenges associated with interpreting PSA test results in various ways—taking the volume of the prostate into account, for example, and tracking how quickly it increases over time. Assays for different molecular forms of PSA, such as proPSA, have also been developed. (Studies have shown that higher levels of proPSA are associated with cancer.) However, these tests serve as adjuncts to PSA, not as replacements.
A few non–PSA-based biomarkers have emerged as possible screening tools. Two of the strongest are prostate cancer antigen 3 (PCA3) and the TMPRSS2:ERG gene fusion.
PCA3 is a noncoding RNA overexpressed by cancerous prostate cells that can be detected in urine. Studies have shown PCA3 to be a robust biomarker, and the U.S. Food and Drug Administration approved a PCA3 test in February 2012 for men considering a repeat biopsy after a negative biopsy, but not for screening.
Unlike PSA, the TMPRSS2:ERG gene fusion, which can be detected in urine, is specific for prostate cancer. However, half of all prostate cancers lack TMPRSS2:ERG, meaning that tests will also need to look for PSA, PCA3, or other biomarkers.
Data assessing the utility of PCA3 and TMPRSS2:ERG for screening large numbers of asymptomatic men over time are lacking. “It's going to be at least 15 or 20 years until we have enough information to determine whether these tests are valid and have any mortality benefit,” predicts Marc Garnick, MD, a medical oncologist and prostate cancer specialist at Beth Israel Deaconess Medical Center in Boston. A supporter of the USPSTF findings, Garnick expressed his views on PSA testing in an article he wrote for the February 2012 issue of Scientific American.
Anthony D'Amico, MD, PhD, a radiation oncologist at Boston's Brigham and Women's Hospital and one of the authors of an editorial criticizing the USPSTF's conclusions, says smarter patient selection is one solution to the overdiagnosis problem. Instead of “throwing out a very important test,” he advocates PSA screening for men at high risk for harboring aggressive and life-threatening prostate cancer, such as black, Hispanic, and Latino men. Screening less often—every 2 years instead of annually—is another option for those at average risk for harboring aggressive prostate cancer. “PSA is a much better test than they give it credit for,” he says.