September 18, 2019 -- Blood testing for levels of prostate-specific antigen (PSA) gets a bad rap, but a targeted approach is gaining support. A large study published online September 16 in European Urology backs routine testing for men with BRCA2 mutations as a means of picking up clinically significant cancer earlier.
The prospective, multinational study -- titled Identification of Men With a Genetic Predisposition to Prostate Cancer (IMPACT) -- examined the role of yearly PSA testing in 2,932 men with a family history of BRCA mutations. The interim results were reported by Dr. Rosalind Eeles, a professor of oncogenetics at the Institute of Cancer Research in London, and colleagues.
In the study, half of the participants were BRCA1 or BRCA2 carriers and half had tested negative. Men with a PSA level greater than 3 ng/mL were offered transrectal biopsy of the prostate.
Based on an analysis performed after four screening rounds, BRCA2 carriers were significantly more likely to get cancer, to be diagnosed at an earlier age, and to have more aggressive disease than BRCA2 noncarriers, the researchers found. Statistically significant differences were not seen between BRCA1 carriers and BRCA1 noncarriers.
"We recommend that male BRCA2 carriers are offered systematic PSA screening," the authors advised.
|IMPACT results: BRCA2 carriers vs. noncarriers|
|End point||BRCA2 carriers||BRCA2 noncarriers||p-value for significant results|
|Cancer incidence per 1,000 person years||19.4||12||0.03|
|Likelihood of having significant disease||77%||40%||0.01|
The researchers estimated that with four screening rounds (at baseline and annually for three years) in BRCA2 carriers between 40 and 54 years of age, 60 men would need to undergo PSA testing to pick up one clinically significant prostate cancer. In addition, screening 13 BRCA2 carriers between the ages of 55 and 69 would pick up one clinically significant prostate cancer. The youngest age at diagnosis for a clinically significant cancer was 41 among BRCA2 carriers and 43 among BRCA1 carriers, which the authors said may mean screening needs to start at a young age.
"Eventually, long-term follow-up data on the clinical benefit of early detection are needed to determine the best starting age," Eeles and colleagues advised.
For now, the jury is still out on PSA testing for BRCA1 carriers, according to the group.
Targeted approach to PSA
The authors noted that PSA testing is commonly done, but it is controversial as a screening test due to its imprecise nature. Risks include unnecessary biopsies and treatments, with associated negative effects, for prostate cancers that men would have died with -- not from. The IMPACT study, however, is testing the feasibility of a targeted approach based on BRCA mutation status and the PSA threshold of 3 ng/mL.
An association between BRCA2 status and prostate cancer risk has long been recognized, but it's been unclear what role BRCA1 plays. Guidelines from the U.S. National Comprehensive Cancer Network advise prostate cancer screening for male BRCA2 carriers starting at age 45, while the guidance for male BRCA1 carriers is more equivocal, the authors wrote.
Eeles and colleagues reported that the positive predictive value of PSA using a threshold of 3 ng/mL was 21% overall, 31% in BRCA2 carriers, and 18% in BRCA2 noncarriers.
Of the total cohort, 13% had a biopsy, and the cancer detection rate was 3.8%. Compliance with the study protocol -- for example, direction to get a biopsy -- was a limitation of the research, the authors acknowledged. The biopsy rate was higher for BRCA2 carriers than noncarriers, which could reflect a bias among health professionals toward further follow-up in those testing positive, Eeles and colleagues suggested.
"The IMPACT study continues to collect screening data, and a further component of the protocol is to offer men the option of undergoing [prostate biopsy] after the completion of five screening rounds, irrespective of the PSA level," they wrote. "This will provide the opportunity to evaluate the number of clinically significant cancers missed in carriers and noncarriers when using a PSA threshold of 3.0 [ng/mL]."