Prostate Cancer Genetics: Ready for Clinical Use?
Serge Ginzburg, MD
For decades, prostate cancer risk (PCa) stratification was based primarily on the architectural pattern of the tumor under low magnification (Gleason score), PSA and DRE.
As the biological basis of cancers becomes elucidated, our ability to associate aberrant genes with PCa development is outpacing our understanding of how to apply this information clinically.
PCa detection in men with BRCA1 and BRCA2 mutations was compared to controls (BRCA1 or BRCA2 negative, but with family history of these mutations) in a recent analysis of the IMPACT trial.1 Using a PSA threshold of 3.0 ng/mL the study noted that 66% of the detected tumors were classified as intermediate or high risk.
Moreover, the 48% positive predictive value (PPV) for biopsy in BRCA2 mutation carriers was double the PPV previously reported in other population screening studies.
In the current study, Castro et al further these observations by comparing the response to the conventional treatment in men with BRCA1 and BRCA2 mutations to those without, deriving the cohorts from EMBRACE and UKPGCS observational studies.2
The authors demonstrate BRCA positivity to independently correlate with worse metastasis-free cancerspecific survival. These studies contribute to the growing body of literature that recognizes the prognostic value of BRCA. Although the overall prevalence of these autosomal dominant mutations is low and the penetrance variable, families are becoming more informed about their genetic signature.
Targeted screening is on the horizon and will ultimately have a favorable impact on identifying high-risk populations. At present, however, the clinical utility of this information remains limited. Until this knowledge gap is closed, electing
preemptive treatments based on one's genetics may be premature.3
Serge Ginzburg, MD, is a urologic oncologist at Albert Einstein Medical Center in Elkins Park, Pa., and an assistant professor at Fox Chase Cancer Center in Philadelphia.
- Bancroft EK, Page EC, Castro E, et al. Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: Results from the initial screening round of the IMPACT Study. Eur Urol. 2014;66:489-499.
- Castro E, Goh C, Leongamornlert D, et al. Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer. Eur Urol. 2014 (published online ahead of print).
- Uzzo RG. Genetic Risk and PCa Treatment. Renal & Urology News. 2013 (12:6).