本研究的目的是通过测量前列腺癌（PCa）可见多参数核磁共振成像（mpMRI）之外的癌变区附近肿瘤抑制基因的DNA甲基化水平，研究与索引病变相邻的癌化领域的程度，从而确定靶向治疗安全区的范围。共有272名患者参与了该研究，其中44名患者的组织样本被纳入癌变领域研究，272名尿液样本被纳入基于尿液的测试开发。利用mpMRI/超声图像融合系统进行了靶向活检。定量分析显示，与距离索引病变10mm的周围组织样本相比，RARB、RASSF1、GSTP1和APC基因的DNA甲基化水平在索引病变中显著增高（p<0.0001）。 值得注意的是，RARB、GSTP1和APC以及RARB、RASSF1、GSTP1和APC生物标志物组合在比较索引病变和距离非癌性前列腺组织20mm的程度的DNA甲基化时表现出最高的敏感性和特异性（AUC均为0.98；p<0.0001）。对潜在尿液生物标志物的分析显示，将所有四种DNA甲基化生物标志物与血清前列腺特异性抗原（PSA）或PSA密度（PSAD）相结合，可以显著提高对临床显著PCa的检测。将四种生物标志物测试与PSAD结合可以实现对临床显著PCa的≥90%敏感性和特异性识别。 因此，本研究建议对于区域靶向手术治疗，与索引病变的安全距离不少于10mm。非侵入性尿液DNA甲基化测试结合PSAD可用于患者的后续随访，但需要进行更大规模的前瞻性研究，并进行外部验证。 ©2023 Wiley Periodicals LLC.

This study aimed to investigate the extent of field cancerization adjacent to index lesions in prostate cancer (PCa) by measuring DNA methylation of selected tumor suppressor genes in the perifocal tissue of PCa not visible on multiparametric magnetic resonanse imaging (mpMRI) for the safe zone of focal therapy identification.A total of 272 patients were enrolled in this study, 44 patients' tissue biosamples were included in the field cancerization research, and 272 urine samples were included in the urine-based test development. Targeted biopsies were performed using the mpMRI/ultrasoundimage fusion system.Quantitative analysis revealed significantly higher DNA methylation levels of RARB, RASSF1, GSTP1 & APC genes in the index lesion compared with perifocal tissue samples 10 mm away from it (p < 0.0001). Notably, the RARB, GSTP1 & APC and RARB, RASSF1, GSTP1 & APC biomarker combinations exhibited the highest sensitivity and specificity comparing the extent of DNA methylation in index lesions and noncancerous prostate tissues 20 mm away (both area under the curve [AUC] = 0.98; p < 0.0001). The analysis of the potential urinary biomarkers showed that the combination of all four DNA methylation biomarkers with prostate-specific antigen (PSA) or PSA density (PSAD) in the blood significantly improves the detection of clinically significant PCa (csPCa). The combination of the four-biomarker test with PSAD allowed the identification of csPCa with ≥90% sensitivity and specificity.Thus, this study suggests that for focal therapy by region target hemi-ablation, the safe distance from the index lesion is no less than 10 mm. Noninvasive urine DNA methylation tests in combination with PSAD could be used for further follow-up of the patients, but larger prospective studies with external validation are needed.© 2023 Wiley Periodicals LLC.