Study of PSA Screening Strategies Looks to Reduce Risks

FP Expert Says Findings Support Changing How Screening is Used

February 11, 2013 03:35 pm Matt Brown

"Smarter" use of prostate-specific antigen (PSA)-based screening for prostate cancer may reduce risks associated with the test, says a study( (abstract) in the Feb. 5 issue of the Annals of Internal Medicine.

[Prostate Cancer definition w/lab bottles]

According to the study, historical uncertainty surrounding the efficacy, effectiveness and safety of PSA screening, coupled with heightened awareness of screening-related harms triggered by the U.S. Preventive Services Task Force (USPSTF) recommendation against routine PSA-based screening, prompted the authors to attempt to identify strategies that would reduce the harms of screening while preserving its effect on detection and survival.

Using a mathematical model, the study authors compared 35 PSA screening strategies used in U.S. and European trials. The candidate screening strategies considered were 32 combinations of two ages to start (40 or 50) and stop (69 or 74) screening, two screening intervals (annual or biennial) and four thresholds for biopsy referral (PSA level of 4.0 mcg per L; PSA level of 2.5 mcg per L; PSA level of 4.0 mcg per L or PSA velocity of 0.35 mcg per L per year; or PSA level greater than 95th percentile for age [2.5, 3.5, 4.5 and 6.5 mcg per L for ages 40-49, 50-59, 60-69 and 70-74, respectively]).

story highlights

  • A modeling study indicates that "smarter" use of prostate-specific antigen (PSA)-based screening for prostate cancer may reduce risks associated with the test.
  • The study authors based their conclusions on a comparison of 35 PSA screening strategies used in U.S. and European trials.
  • An accompanying editorial and a family physician expert agree, however, that the study's results are not likely to change clinical practice.

Starting with a baseline lifetime risk of death from prostate cancer of 2.86 percent, the study found that

  • a reference strategy that screens men ages 50-74 years annually with a PSA threshold for biopsy referral of 4 mcg perL reduces the risk for prostate cancer death to 2.15 percent, while yielding a 3.3 percent risk of overdiagnosis;
  • a strategy that uses a higher PSA threshold for biopsy referral in older men achieves a similar risk for prostate cancer death (2.23 percent) but reduces the risk for overdiagnosis to 2.3 percent; and
  • a strategy that screens biennially, with longer screening intervals for men with low PSA levels, achieves similar risks for prostate cancer death (2.27 percent) and overdiagnosis (2.4 percent), but reduces total tests by 59 percent and false-positive results by 50 percent.

"Compared with standard screening, PSA screening strategies that use higher thresholds for biopsy referral for older men and that screen men with low PSA levels less frequently can reduce harms while preserving lives saved," the authors conclude.

In an accompanying editorial(, John Concato, M.D., M.P.H., an internist at the Veterans Affairs Connecticut Healthcare System in West Haven, says the limitations of the analysis leave questions unanswered and dilute its ability to inform the PSA screening debate.

"The model itself is mathematically meticulous and conceptually interesting, and the conclusions are reasonable -- but the corresponding clinical relevance is limited," Concato notes. "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."

USPSTF Co-vice Chair Michael LeFevre, M.D., M.S.P.H., echoes Concato's sentiment, telling AAFP News Now that the study doesn't add any new information to what physicians and researchers already know about the benefits and harms of prostate cancer screening.

"Bottom line, the task force reached the conclusion that the potential benefit of prostate cancer screening does not outweigh the harm and this study certainly does not change that," LeFevre says. "It is also important to remember that (the authors of the Annals study) didn't actually study anybody. It is just a mathematical exercise, and it supports what is intuitively obvious: Screen less, biopsy less, and do less harm."

LeFevre, who is a family physician in Columbia, Mo., contends that the study supports the notion that physicians can lower the harms of prostate cancer screening by changing the way screening is used -- either by raising the threshold for biopsy, changing the frequency of screening or by putting an age cutoff on screening. However, although any one of those things is likely to reduce the harms associated with prostate cancer screening, physicians still do not know how doing those things would increase what is considered to be a very small possibility of benefit.

"The results from the U.S. and European studies were mixed," LeFevre says. "The European study showed a very small benefit, and the U.S. trial showed none.

"For those who continue to screen, a higher threshold for biopsy or less frequent testing will result in fewer false-positive results and less overdiagnosis and, therefore, reduce the harm."