Gene Mutations May Enable Targeted PSA Screening

The BRCA2 gene mutation is associated with a significantly increased likelihood of PCa.
The BRCA2 gene mutation is associated with a significantly increased likelihood of PCa.

Men who have the BRCA2 gene mutation are significantly more likely than non-carriers to have intermediate- or high-risk prostate cancer (PCa) found on prostate biopsy, according to the preliminary findings of an international study. The results support the use of targeted PSA screening for BRCA2 carriers, researchers concluded.

Previous research has found that PCa is more likely to develop in men with BRCA1 or BRCA2 gene mutations than in those without these mutations.

The study enrolled 2,481 men from 62 centers in 20 counties. The study population consisted of 791 BRCA1 carriers, 531 BRCA1 controls, 731 BRCA2 carriers, and 428 BRCA2 controls. A total of 199 subjects (8%) presented with a PSA level above 3.0 ng/mL and were offered a prostate biopsy. In all, 162 biopsies were performed and 59 patients were diagnosed with PCa (18 BRCA1 carriers, 10 BRCA1 controls, 24 BRCA2 carriers, and seven BRCA2 controls).

The positive predictive value (PPV) of a prostate biopsy using a PSA threshold of 3.0 ng/mL for detecting intermediate- and high-risk PCa was 2.38% for men carrying the BRCA2 mutation compared with 0.71% for controls (men who tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families).

“These early findings indicate that the tumours detected [in BRCA2 carriers] are more likely to need treatment based on national guidelines for management of more aggressive PCa,” Rosalind A. Eeles, PhD, of The Institute of Cancer Research in London, U.K., and colleagues concluded in an online report in European Urology. The results are from the initial screening round of the IMPACT study.

The overall PPV of biopsies using the 3.0 ng/mL PSA threshold was 36% (59 of 162 biopsies). The PPV was 37.5% for BRCA1 carriers, 23.3% for BRCA1 controls, 48% for BRCA2 carriers, and 33.3% for BRCA2 controls. The researchers found no statistically significant difference among the groups. Although the observed differences in PCa detection rates between carriers and controls were not statistically significant, the trend is clear, they wrote. With larger numbers of PCa cases in the follow-up phase of the study (five years), “these differences, if sustained, are likely to be significantly.”

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