1. PSA and BRCA: an IMPACT update
Men with germline BRCA1 and BRCA2 mutations not only have an increased risk of prostate cancer, but research also suggests that these men develop more aggressive disease, are younger at diagnosis, have a higher rate of lymph node involvement and distant metastases at diagnosis, and higher mortality rates. Moreover, BRCA2 mutant localised cancer has a mutational profile that more closely resembles metastatic than localised disease, therefore supporting early detection in this at-risk population.
The IMPACT study is an international multi-centre study evaluating the role of PSA screening in men with a BCRA1 or BRCA2 mutation. To date, around 3000 men have been recruited from 20 countries across the world. The objective of the present study was to establish whether PSA values and/or PSA velocity (PSAV) were associated with prostate cancer and aggressive tumours among men at risk enrolled in the IMPACT trial.
The study found that overall, the PSA level and PSAV at diagnosis were higher in men diagnosed with cancer (3.7 vs 0.9 ng/ml, p<0.0001 and 0.56 vs 0.02 ng/ml/year, respectively). In addition, whilst there was a significant interaction between PSA level at diagnosis and BRCA status (p=0.031), PSAV did not provide any additional information for BRCA carriers (p=0.4). However, PSAV proved predictive of any grade cancer within the group of BRCA2 carriers (p=0.024), suggesting that a high PSAV in an individual with a BRCA2 mutation could be used both as an indicator of prostate cancer and as an indication for biopsy, leading to diagnosis of lower grade cancers in BRCA2 carriers.
In summary, PSA is more predictive of prostate cancer in BRCA carriers than non-carriers. PSAV was not found to be an independent prognostic factor in BRCA carriers, and this study found no evidence that PSAV aids decision making for indication of biopsy or frequency of follow-up in BRCA carriers.