LBA-08 SCREENING OF BRCA2 MUTATED MEN FOR DETECTION OF PROSTATE CANCER: PRELIMINARY RESULTS FROM A NATIONAL HIGH VOLUME CANCER CENTRE

Abstract

INTRODUCTION AND OBJECTIVES: Up to 10% of cases of Prostate Cancer (PCa) are hereditary. Germline pathogenic mutations in BRCA2 gene confer the highest risk (2.5 to 8.6 fold in men < 65 yr) =1-3]. Beyond periodic Prostate Specific Antigen (PSA) dosage and digital rectal examination (DRE), a targeted screening for carriers is still undefined. Prostate health index (PHI), a combination of the tPSA, fPSA and proPSA tests, may be a more accurate biomarker than PSA only to detect PCa =4]. We evaluated how to better screen BRCA2 mutated men for PCa. METHODS: We reviewed the genealogical trees of all women who tested positive for germline BRCA2 pathogenic mutation at our clinic. We offered targeted BRCA2 mutational analysis to all first/second degree relative men between 40 and 69 yr. A targeted screening program (annual PSA and PHI dosages and DRE) was proposed to all men who tested positive. If PSA and/or PHI values were out of range (>4ng/mg and >20, respectively) we proceeded with a multiparametric Magnetic Resonance Imaging (mpMRI) and fusion biopsy of suspected lesions. RESULTS: From June 2008 to October 2018 610 breast/ovarian cancer patients underwent BRCA1/2 test: 35 (5.7%) tested positive for BRCA1 pathogenic mutation, 32 (5.2%) for BRCA2 pathogenic mutation. From October 2017 90 relatives were checked for the familial mutation, 23 (26%) (12 women and 11 men) tested positive for BRCA2 pathogenic mutation. All the 11 men (median age 48 yr, IQR 44 to 60) accepted to join our screening program. During the first year all men had negative DRE. Median PSA was 0.54 (IQR 0.43 to 0.98), median PHI was 15.93 (IQR 12.00 to 24.06). One man had PHI out of range and had an mpMRI that resulted negative. During the second year 4 men underwent screening: they had negative DRE. Median PSA was 0.57 (IQR 0.38-0.77), median PHI was 16.88 (IQR 11.87-21.90). Two men had PHI out of range and underwent mpMRI. Both of them were postive for lesions PIRADS IV and underwent fusion biopsy; one was positive for prostate adenocarcinoma Greason 4+3. CONCLUSIONS: An accurate evaluation of the genealogical trees of breast/ovarian cancer BRCA2 mutated patients allows to identify male relatives potentially carriers of the same mutation. These patients have a high lifetime risk of PCa and require an appropriate screening, currently absent. Our approach may be leveraged as proof of concept of selection and subsequent screening program in carriers of BRCA2 mutations.