Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia.
Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea.
Eur Urol Oncol. 2021 Dec;4(6):927-942. doi: 10.1016/j.euo.2021.10.003. Epub 2021 Nov 6.
During the past decade, several urinary biomarker tests (UBTs) for bladder cancer have been developed and made commercially available. However, none of these is recommended by international guidelines so far.
To assess the diagnostic estimates of novel commercially available UBTs for diagnosis and surveillance of non-muscle-invasive bladder cancer (NMIBC) using diagnostic test accuracy (DTA) and network meta-analysis (NMA).
PubMed, Web of Science, and Scopus were searched up to April 2021 to identify studies addressing the diagnostic values of UBTs: Xpert bladder cancer, Adxbladder, Bladder EpiCheck, Uromonitor and Cxbladder Monitor, and Triage and Detect. The primary endpoint was to assess the pooled diagnostic values for disease recurrence in NMIBC patients using a DTA meta-analysis and to compare them with cytology using an NMA. The secondary endpoints were the diagnostic values for high-grade (HG) recurrence as well as for the initial detection of bladder cancer.
Twenty-one studies, comprising 7330 patients, were included in the quantitative synthesis. In most of the studies, there was an unclear risk of bias. For NMIBC surveillance, novel UBTs demonstrated promising pooled diagnostic values with sensitivities up to 93%, specificities up to 84%, positive predictive values up to 67%, and negative predictive value up to 99%. Pooled estimates for the diagnosis of HG recurrence were similar to those for the diagnosis of any-grade recurrence. The analysis of the number of cystoscopies potentially avoided during the follow-up of 1000 patients showed that UBTs might be efficient in reducing the number of avoidable interventions with up to 740 cystoscopies. The NMA revealed that diagnostic values (except specificity) of the novel UBTs were significantly higher than those of cytology for the detection of NMIBC recurrence. There were too little data on UBTs in the primary diagnosis setting to allow a statistical analysis.
Our analyses support high diagnostic accuracy of the studied novel UBTs, supporting their utility in the NMIBC surveillance setting. All of these might potentially help prevent unnecessary cystoscopies safely. There are not enough data to reliably assess their use in the primary diagnostic setting. These results have to be confirmed in a larger cohort as well as in head-to-head comparative studies. Nevertheless, our study might help policymakers and stakeholders evaluate the clinical and social impact of the implementation of these tests into daily practice.
Novel urinary biomarker tests outperform cytology with the potential of improving routine clinical practice by preventing unnecessary cystoscopic examinations during the surveillance of non-muscle-invasive bladder cancer.
在过去的十年中，已经开发出几种用于膀胱癌的尿液生物标志物检测（UBT）并已商业化。然而，到目前为止，国际指南都没有推荐这些检测。
使用诊断准确性（DTA）和网络荟萃分析（NMA）评估新型商业 UBT 用于诊断和监测非肌层浸润性膀胱癌（NMIBC）的诊断评估。
截至 2021 年 4 月，在 PubMed、Web of Science 和 Scopus 上搜索了研究 UBT 诊断价值的文章：Xpert 膀胱癌、Adxbladder、Bladder EpiCheck、Uromonitor 和 Cxbladder Monitor，以及 Triage 和 Detect。主要终点是使用 DTA 荟萃分析评估 NMIBC 患者疾病复发的汇总诊断价值，并使用 NMA 将其与细胞学进行比较。次要终点是评估高危（HG）复发以及膀胱癌初始检测的诊断价值。
共有 21 项研究，涉及 7330 名患者，纳入了定量综合分析。在大多数研究中，存在不确定的偏倚风险。对于 NMIBC 监测，新型 UBT 具有有前景的汇总诊断价值，灵敏度高达 93%，特异性高达 84%，阳性预测值高达 67%，阴性预测值高达 99%。HG 复发的汇总估计值与任何等级复发的诊断值相似。对 1000 例患者随访期间潜在可避免的膀胱镜检查数量的分析表明，UBT 可能通过减少多达 740 例膀胱镜检查，从而提高效率。NMA 显示，新型 UBT 的诊断价值（特异性除外）明显高于细胞学用于检测 NMIBC 复发。关于新型 UBT 用于原发性诊断的研究数据太少，无法进行统计分析。
我们的分析支持所研究的新型 UBT 具有较高的诊断准确性，支持其在 NMIBC 监测中的实用性。所有这些都可能有助于安全地防止不必要的膀胱镜检查。关于原发性诊断的研究数据不足，无法可靠评估其使用情况。这些结果需要在更大的队列中以及头对头的比较研究中得到证实。尽管如此，我们的研究可能有助于决策者和利益相关者评估将这些检测纳入日常实践的临床和社会影响。
新型尿液生物标志物检测优于细胞学，通过在非肌层浸润性膀胱癌的监测期间预防不必要的膀胱镜检查，有可能改善常规临床实践。
