Urine-based tumor markers are not routinely used in the diagnosis and surveillance of bladder cancer. The main limitation of urinary markers has been a lack of clarity regarding clinical benefit.
To review the indications for urinary marker use, barriers to marker utilization, and clinical trial designs for markers available for detection (hematuria populations) and surveillance (bladder cancer populations). The study aim was to facilitate an optimal trial design that could change clinical practice.
A PubMed search was conducted on February 17, 2018, using the MeSH search terms "Urinary Bladder Neoplasms" [Mesh] AND "Biomarkers" [Mesh] AND "Urine" [Mesh] yielded 127 articles, of which only two also fulfilled the search term "Randomized Controlled Trial" [Publication Type]. Neither of these two articles examined clinical outcomes for patients but rather focused on the performance characteristics of the urinary marker. For the search terms "Hematuria" [Mesh] AND "Randomized Controlled Trial" [Publication Type] AND "Urinary Bladder Neoplasms" [Mesh] yielded 12 articles, none of which used randomization with the outcome of interest being a clinical endpoint.
Several potential designs for urinary marker trials were developed for detection and surveillance of bladder cancer. A marker-based approach compared to usual care for evaluation of hematuria in a primary care setting could reduce unnecessary cystoscopy in patients with low risk and expedite care in patients with higher risk. For bladder cancer surveillance, marker-based approaches could reduce cystoscopy for patients with low-grade disease and potentially improve detection for patients with high risk.
Urinary markers are not currently routinely used owing to the absence of level 1 evidence supporting incorporation of urinary markers into protocols for detection or surveillance of bladder cancer. This review provides practical designs for studies that could demonstrate superiority of marker-based approaches over current clinical care. The sample sizes required for these studies are no greater than many of those accrued for previous urinary marker studies, but the proposed trial concepts require planning and a willingness to risk failure of the marker to demonstrate the desired benefits.
In this review we discuss current limitations in the use of urinary markers for detection and surveillance of bladder cancer. We identify potential studies that could demonstrate a clinical benefit of the use of markers in improving detection of bladder cancer by reducing evaluation of patients unlikely to have cancer or expediting identification of cancer. For surveillance, a marker trial could improve identification of bladder cancer or reduce cystoscopy in patients with low risk.
European urology oncology. 2018 May 15 [Epub]
Yair Lotan, Peter C Black, Laura Caba, Sam S Chang, Michael S Cookson, Siamak Daneshmand, Ashish M Kamat, James M McKiernan, Raj S Pruthi, Chad R Ritch, Gary D Steinberg, Robert S Svatek, Ellen C Zwarthoff
Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA. Electronic address: ., Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada., MDxHealth Inc., Irvine, CA, USA., Vanderbilt University Medical Center, Nashville, TN, USA., Department of Urology, The University of Oklahoma Health Sciences Center and The Stephenson Cancer Center, Oklahoma City, OK, USA., USC Institute of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA., MD Anderson Cancer Center, Houston, TX, USA., Department of Urology, Columbia University Irving Medical Center, New York, NY, USA., Department of Urology, University of North Carolina at Chapel Hill, and Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA., Department of Urology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA., Department of Surgery, Section of Urology, The University of Chicago, Chicago, IL, USA., Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA., Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.