Abstract IA07: Potential benefits of and obstacles to use of urine-based tumor markers
Authors: Yair Lotan
Journal: Clinical Cancer Research (2020)

Abstract There are many potential uses of urine-based tumor markers in improving detection and surveillance of bladder cancer. Prior to incorporation of urine markers into clinical care, it is important to demonstrate improved efficacy over standard clinical tools. The main areas where urine markers may improve care is in triaging patients with hematuria who need evaluation, reducing frequency of cystoscopy in patients with low-grade disease, improving detection of high-grade patients, and improving prediction of outcomes in patients with bladder cancer. There are currently limitations in white light cystoscopy, especially in detection of carcinoma in situ (CIS). Also, the most widely used urine marker, cytology, has low sensitivity for detecting low-grade cancer and can miss up to 40% of high-grade bladder cancer. Most urine markers have improved sensitivity over urine cytology but reduced specificity. The prevalence of disease impacts the positive and negative predictive values of these tests. For hematuria, the prevalence of cancer is very low in microhematuria patients; as such, the positive predictive value of urine markers is low. Clinicians need markers to provide clinically useful information by either having a high positive predictive value or high negative predictive value (NPV). In the context of microhematuria, many patients are not adequately evaluated and this can result in delays in diagnosis. A urine marker with a high NPV could reduce need for cystoscopy for low-risk patients and enrich the cohort of patients more likely to have cancer. For surveillance, the sensitivity of urine markers has not been sufficient to replace cystoscopy. It is possible that replacing some cystoscopy procedures by alternating a marker with cystoscopy for patients with low-grade disease may be possible, but trials are needed to demonstrate the safety and efficacy of this approach. In high-grade patients, there is need for improved detection of recurrent tumors, especially CIS, since white light cystoscopy has been shown to miss tumors compared to enhanced cystoscopy. A high-performing urine marker could improve detection, but appropriate studies need to be performed to demonstrate sufficient PPV to justify modifying clinical care. There is also a potential role for using markers to improve management of patients with atypical cytology or cystoscopic findings. They could also improve prediction of outcomes in patients with high-grade disease, especially in those patients treated with intravesical therapies. In order for urine markers to be incorporated into guidelines, it is important to develop appropriate trials to validate their utility. There is also a need to consider overall cost of care and patient perspectives. Citation Format: Yair Lotan. Potential benefits of and obstacles to use of urine-based tumor markers [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA07.