Data from: Distinct longitudinal patterns of urine tumor DNA in patients undergoing surveillance for bladder cancer

Abstract: Cystoscopy is the gold standard for surveillance of non-muscle invasive bladder cancer (NMIBC), but is invasive and has suboptimal accuracy. The aim of this study was to investigate the potential of urine tumor DNA (utDNA) to replace cystoscopy for surveillance of bladder cancer recurrences. In this longitudinal, prospective and observational study, 47 patients were followed for recurrence for two years, involving droplet digital PCR (ddPCR) analysis of utDNA using the BladMetrix DNA methylation biomarker test at each cystoscopy control. utDNA was detected in 21/23 recurrences (91% sensitivity), including 5/5 T1, T2 and CIS tumors (100%) and 10/12 Ta tumors (83%), with <1% false negative test results. Importantly, utDNA analysis showed potential to reduce the number of cystoscopies by 55%, benefitting 79% of the patients. Eleven of 23 recurrences (48%) were detected earlier with utDNA than with cystoscopy, and distinct patterns of residual utDNA post-surgery indicated minimal residual disease (MRD) or field effect in 6% and 15% of the patients, respectively. In conclusion, utDNA analysis shows high sensitivity to detect tumor recurrence, potential to reduce the number of cystoscopies, and promise to guide patient-specific surveillance regimes.摘要： 膀胱镜检查是非肌层浸润性膀胱癌（non-muscle invasive bladder cancer, NMIBC）监测的金标准，但具有侵入性且准确性欠佳。本研究旨在探究尿液肿瘤DNA（urine tumor DNA, utDNA）替代膀胱镜检查用于膀胱癌复发监测的潜力。本项纵向前瞻性观察研究共纳入47例患者，随访两年以监测肿瘤复发情况，每次膀胱镜检查随访时均采用BladMetrix DNA甲基化生物标志物检测试剂盒，通过液滴数字PCR（droplet digital PCR, ddPCR）对尿液肿瘤DNA进行分析。结果显示，23例复发患者中检出尿液肿瘤DNA共21例（灵敏度91%），其中T1、T2期及原位癌（carcinoma in situ, CIS）肿瘤共5例全部检出（灵敏度100%），Ta期肿瘤12例中检出10例（灵敏度83%），假阴性率低于1%。值得注意的是，尿液肿瘤DNA分析有望减少55%的膀胱镜检查次数，使79%的患者获益。23例复发患者中有11例（48%）经尿液肿瘤DNA检测早于膀胱镜检查被发现；术后残留尿液肿瘤DNA的不同模式分别提示6%和15%的患者存在微小残留病灶（minimal residual disease, MRD）或肿瘤场效应。综上，尿液肿瘤DNA分析在检测肿瘤复发方面灵敏度较高，具备减少膀胱镜检查次数的潜力，并有望指导个体化的患者监测方案。