为评估使用最近开发的血液和尿液分子生物标记物与临床信息以及多参数磁共振成像（mpMRI）相结合的方法来管理高遗传风险男性早期诊断癌症（PCa）的不同情景。此研究纳入了322名高遗传风险患者（家族或个人癌症史或易感性生殖细胞突变），主要结果是PCa检测率（阳性活检）或临床意义明显的PCa检测率（具有国际泌尿学病理学协会[ISUP]级别>1的活检）。临床参数包括年龄，体重指数，血统和生殖细胞突变状态，评估了mpMRI，前列腺特异性抗原密度（PSAD），前列腺健康指数和尿标记物（前列腺癌相关3，SelectMdx™和T2:ERG分数）。计算了每个标记物在临床实践中推荐的截断值的敏感性（Se）和特异性（Sp）。使用基于互信息的监督贝叶斯网络方法计算了每个过程和情景的诊断准确性比较和直接影响贡献。mpMRI前列腺成像-报告和数据系统（PI-RADS）评分≥3的检测PCa（82% vs 61%）和检测ISUP级别>1病变（96% vs 80%）的Se高于mpMRI PI-RADS评分≥4。 mpMRI PI-RADS评分≥3对于检测临床意义明显的PCa而言比PSA水平≥3 ng / mL（Se 96％，Sp 53％ vs Se 91％，Sp 8％）表现更好。如果mpMRI结果为阴性，则监督贝叶斯网络方法显示尿标记物（准确率相同）和PSAD≥0.10 ng / mL/mL是决定活检的最有用的指标。我们发现，筛查高遗传风险PCa的男性必须基于mpMRI，而不是基于PSA水平> 3 ng/mL的预筛选，以避免错过太多ISUP级别>1的肿瘤并显着减少不必要的活检数量。然而，当mpMRI为阴性时，尿标记物或PSAD≥0.10 ng/mL/mL可以增加ISUP级别>1癌症的检出率。我们建议从40岁开始为高遗传风险的男性进行基线mpMRI。 © 2023年BJU International。

To evaluate different scenarios for the management of early diagnosis of cancer (PCa) in men at high genetic risk, using recently developed blood and urinary molecular biomarkers in combination with clinical information alongside multiparametric magnetic resonance imaging (mpMRI).A total of 322 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 International Society of Urological Pathology [ISUP] grade >1). Clinical parameters included age, body mass index, ancestry, and germline mutational status, mpMRI, prostate-specific antigen density (PSAD), Prostate Health Index and urinary markers (Prostate Cancer Associated 3, SelectMdx™ and T2:ERG score) were assessed. Sensitivity (Se) and specificity (Sp) 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 a supervised Bayesian network approach.A mpMRI Prostate Imaging-Reporting and Data System (PI-RADS) score ≥3 showed higher Se than mpMRI PI-RADS score ≥4 for detection of PCa (82% vs 61%) and for the detection of ISUP grade >1 lesions (96% vs 80%). mpMRI PI-RADS score ≥3 performed better than a PSA level of ≥3 ng/mL (Se 96%, Sp 53% vs 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 of ≥0.10 ng/mL/mL were the most useful indicators of decision to biopsy.We found that screening men at high genetic risk of PCa must be based on mpMRI without pre-screening based on a PSA level of >3 ng/mL, to avoid missing too many ISUP grade >1 tumours and to significantly reduce the number of unnecessary biopsies. However, urinary markers or a PSAD of ≥0.10 ng/mL/mL when mpMRI was negative increased the detection of ISUP grade >1 cancers. We suggest that a baseline mpMRI be discussed for men at high genetic risk from the age of 40 years.© 2023 BJU International.