PSA TESTING-GET SMARTER

In the quest to identify men at the greatest risk for prostate cancer, more aggressive approaches may not be the answer. Instead, some "smarter" strategies proposed in a new study could reduce potential harms associated with PSA testing without diminishing the estimated percentage of lives saved.

There is little consensus on the optimal approach to prostate-specific antigen (PSA) testing, and the US Preventive Services Task Force recently stated that the current protocol produces more harm than good. Therefore, Roman Gulati, MS, from the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, and colleagues designed a mathematical model to determine the best combination of testing parameters. They reported their findings online February 4 in the Annals of Internal Medicine.

"Few data exist to help clinicians have nuanced conversations with patients about whether and how to have prostate cancer screening," the authors write.

"Data from this study may inform conversations clinicians have with men about whether and how they should be screened," they continue.

The team used microsimulation modeling to identify potentially smarter screening strategies. They assessed 32 different permutations of PSA testing variables: age to start screening (eg, 40 vs 50 years), frequency of subsequent testing, age at which to stop testing, and different PSA cutoff values for biopsy referral. They also assessed screening recommendations from the American Cancer Society and the National Comprehensive Cancer Network.

Compared with a reference strategy of annual screening for men aged 50 to 74 years with a PSA cutoff of 4.0 μg/L for biopsy, more aggressive strategies decrease prostate cancer mortality. However, the authors write, "the harms of unnecessary biopsies, diagnoses, and treatments may be unacceptable."

Instead, less frequent testing and more conservative considerations for biopsy, particularly in older men, translated into "substantial improvements" in the risk–benefit tradeoff of PSA testing, especially with regard to preservation of screening's survival advantage. For example, the researchers determined that screening after age 69 years and up to age 74 years using an age-dependent PSA cutoff reduced risk for overdiagnosis by one third compared with the reference protocol (from 3.3% to 2.3%). At the same time, the risk for prostate cancer death increased slightly, from 2.15% in the reference protocol to 2.3%.

"The model itself is mathematically meticulous and conceptually interesting, and the conclusions are reasonable — but the corresponding clinical relevance is limited," John Concato, MD, MPH, from the Veterans Affairs Connecticut Healthcare System, West Haven, and Yale University, New Haven, Connecticut, writes in an accompanying editorial. "The results, presented as tradeoffs and involving calculations that often differ by only a fraction of a percentage point, are not likely to change clinical practice."

An inability to assess cancer grade progression or to assess stages beyond local–regional vs distant were among the potential limitations of the study.

The National Cancer Institute and the Centers for Disease Control and Prevention funded the study. The study authors and Dr. Concato have disclosed no relevant financial relationships.

Ann Intern Med. Published online February 4, 2013.