Clinical performance of MRI & biomarkers for prostate cancer diagnosis in men at high genetic risk.

ObjectivesTo evaluate different scenarios for the management of early diagnosis of prostate cancer (PCa) in men at high genetic risk, using recently developed blood and urinary molecular biomarkers in combination with clinical information alongside multiparametric MRI (mpMRI).Patients and methodsThree hundred and twenty-two patients with a high genetic risk (familial or personal history of cancers or a predisposing germline variant) were included in this study. The primary outcome was the detection rates of PCa (positive biopsy) or clinically significant PCa (biopsy with ISUP>1). Clinical parameters included age, body mass index, ancestry, and germline mutational status. mpMRI, PSA density (PSAD), phi and urinary markers (PCA3™, SelectMdx™ and T2:ERG score) were assessed. Sensitivity and specificity for each marker at their recommended cut-off for clinical practice were calculated. Comparison between diagnoses accuracy of each procedure and scenario was computed using mutual information based and direct effect contribution using supervised Bayesian Network approach.ResultsmpMRI PI-RADS≥3 showed higher sensitivity (Se) than mpMRI PI-RADS≥4 for detection of PCa (82%, versus 61%) and for detection of ISUP>1 lesions (96% versus 80%). mpMRI PI-RADS≥3 performed better than PSA≥3ng/mL (Se 96%, Sp 53% versus Se 91%, Sp 8%) for detection of clinically significant PCa. In case of negative mpMRI results, the supervised Bayesian Network approach showed that urinary markers (with the same accuracy for all) and PSAD≥0.1ng/mL/cc were the most useful indicators of decision to biopsy.ConclusionsWe found that screening men at high genetic risk for PCa must be based on mpMRI without pre-screening based on PSA>3ng/mL, to avoid missing too much ISUP>1 tumours and to significantly reduce the number of unnecessary biopsies. However, urinary markers or PSAD≥0.1ng/mL/cc when mpMRI was negative increased the detection of ISUP>1 cancers. We suggest that a baseline mpMRI be discussed for men at high genetic risk from 40 years-old.