SAN FRANCISCO—Preliminary results from the initial screening round of the IMPACT study support the use of targeted prostate-specific antigen (PSA) screening based on BRCA genotype, which can yield “a high proportion of aggressive disease,” investigators concluded at the 2014 Genitourinary Cancers Symposium.
The first year’s results, for all men at study enrollment, “indicate that the majority of BRCA1 and BRCA2 mutation carriers diagnosed with prostate cancer at biopsy had developed clinical significantly disease, requiring radical treatment,” noted Christos Mikropoulos, MSc, of the Division of Genetics and Epidemiology at the Institute of Cancer Research, Sutton, United Kingdom, on behalf of the IMPACT Collaborators.
IMPACT—Identification of Men with a genetic Predisposition to Prostate Cancer: Targeted screening in men at higher genetic risk and controls—is an international consortium of 62 centers in 20 countries evaluating the use of targeted prostate cancer screening in men with BRCA1/2 mutations.
The study recruited 2,481 men between the ages of 40 and 69 years with germline BRCA1/2 mutations (791 BRCA1 and 731 BRCA2 carriers)—who have a higher risk of developing prostate cancer—and a control group that tested negative for a BRCA1/2 mutation (531 BRCA1 and 428 BRCA2 controls).
All men underwent PSA testing at enrollment; those with a PSA greater than 3.0 ng/mL (defined as the threshold) were offered prostate biopsy. Of the 199 (8%) with a PSA greater than 3.0 ng/mL, 162 biopsies were performed and 59 cases of prostate cancer diagnosed; 66% of the tumors were classified as intermediate- or high-risk disease. The cases were from 18 BRCA1 carriers, 10 BRCA1 controls, 24 BRCA2 carriers, and seven BRCA2 controls.
“The positive predictive value for biopsy using a PSA threshold of 3.0 ng/mL in BRCA2 mutation carriers was 48%, double that reported in population screening studies,” Mikropoulos reported. “A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers using this threshold.”
He said after 5 years of screening, all men are offered a biopsy regardless of PSA level.
“The IMPACT screening network will be useful for targeted prostate cancer screening studies in men with germline genetic risk variants as they are discovered,” the investigators concluded.
The 2014 Genitourinary Cancers Symposium is sponsored by the the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO).