ImportanceAn accurate noninvasive biomarker test is needed for the early diagnosis of bladder cancer.ObjectiveTo evaluate the performance of a urinary DNA methylation test (PENK methylation) and compare its diagnostic accuracy with that of the nuclear matrix protein 22 (NMP22) test or urine cytology test.Design, Setting, and ParticipantsIn this prospective multicenter study at 10 sites in the Republic of Korea, individuals 40 years and older with hematuria undergoing cystoscopy within 3 months between March 11, 2022, and May 30, 2024, participated. The study participants were evaluated for bladder cancer using a urinary DNA methylation test.ExposureUrinary DNA methylation test, NMP22 test, and urine cytology test.Main Outcomes and MeasuresThe primary outcomes were the sensitivity and specificity of the urinary DNA methylation test for high-grade or invasive bladder cancer. Secondary objectives included the accuracy of the test for overall bladder cancer (all stages and grades) and the comparison of sensitivities and specificities for bladder cancer between the urinary DNA methylation test and the NMP22 test or urine cytology test.ResultsAmong the 1099 participants, 614 (55.9%) were male; participants had a mean (SD) age of 65 (10) years. Of the 1099 participants, 219 and 176 participants had bladder cancer and high-grade or invasive bladder cancer, respectively. The urinary DNA methylation test had sensitivity and specificity for high-grade or invasive bladder cancer of 89.2% (95% CI, 84.6%-93.8%) and 87.8% (95% CI, 85.6%-89.9%), respectively. Sensitivity and specificity for overall bladder cancer were 78.1% (95% CI, 72.6%-83.6%) and 88.8% (95% CI, 86.7%-90.8%), respectively. The positive predictive value for high-grade or invasive bladder cancer was 61.3% (95% CI, 55.4%-67.3%), and the negative predictive value was 97.6% (95% CI, 96.6%-98.7%). In comparison with the NMP22 test or urine cytology test, the urinary DNA methylation test showed significantly superior sensitivity for high-grade or invasive bladder cancer and overall bladder cancer.Conclusions and RelevanceIn this prospective multicenter study of individuals with hematuria, the urinary DNA methylation test showed 89% sensitivity for detecting high-grade or invasive bladder cancer, outperforming the NMP22 test or urine cytology test with high specificity. While this test had an excellent negative predictive value, its positive predictive value was suboptimal.

中文翻译：

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用于膀胱癌诊断的尿 DNA 甲基化检测


重要性膀胱癌的早期诊断需要准确的无创生物标志物测试。目的评价尿 DNA 甲基化试验 （PENK 甲基化） 的性能，并将其诊断准确性与核基质蛋白 22 （NMP22） 或尿液细胞学检测进行比较。设计、设置和参与者在大韩民国 10 个地点进行的这项前瞻性多中心研究中，40 岁及以上的血尿患者在 2022 年 3 月 11 日至 2024 年 5 月 30 日期间的 3 个月内接受了膀胱镜检查。使用尿液 DNA 甲基化测试评估研究参与者是否患有膀胱癌。暴露尿液 DNA 甲基化测试、NMP22 测试和尿液细胞学测试。主要结局和测量主要结局是尿 DNA 甲基化试验对高级别或浸润性膀胱癌的敏感性和特异性。次要目标包括总体膀胱癌 （所有分期和等级） 检测的准确性以及尿 DNA 甲基化检测与 NMP22 检测或尿液细胞学检测之间对膀胱癌的敏感性和特异性的比较。结果在 1099 名参与者中，男性 614 名 （55.9%）;参与者的平均 （SD） 年龄为 65 （10） 岁。在 1099 名参与者中，分别有 219 名和 176 名参与者患有膀胱癌和高级别或浸润性膀胱癌。尿 DNA 甲基化试验对高级别或浸润性膀胱癌的敏感性和特异性分别为 89.2% （95% CI，84.6%-93.8%） 和 87.8% （95% CI，85.6%-89.9%）。对总体膀胱癌的敏感性和特异性分别为 78.1% （95% CI， 72.6%-83.6%） 和 88.8% （95% CI， 86.7%-90.8%）。高级别或浸润性膀胱癌的阳性预测值为 61.3% （95% CI， 55.4%-67.3%），阴性预测值为 97.6% （95% CI，96.6%-98.7%）。与 NMP22 检测或尿液细胞学检测相比，尿 DNA 甲基化检测对高级别或浸润性膀胱癌和整体膀胱癌的敏感性显著优越。结论和相关性在这项针对血尿患者的前瞻性多中心研究中，尿 DNA 甲基化检测显示检测高级别或浸润性膀胱癌的敏感性为 89%，优于 NMP22 检测或尿液细胞学检测，特异性高。虽然该测试具有出色的阴性预测值，但其阳性预测值并不理想。