Many urine markers have been evaluated and also FDA-approved in the context of surveillance for recurrent bladder cancer. However, while they exhibit excellent sensitivity, particularly for lower grade tumors, their specificity is still lower than that of urine cytology, and although cytology’s sensitivity for intermediate- and high-risk cancer may approach 80%, its level is low in detecting low-risk cancer (approximately 20%).111, 130 Thus, this low sensitivity renders cytology of little use in this context.131 While ImmunoCyt™ appears to have the highest sensitivity and specificity in the context of surveillance, the specificity still falls short of urine cytology. Since recurrent bladder tumors detected during surveillance tend to be smaller than primary tumors, the amount of protein expressed by these small tumors is also less. This has led to the suggestion that lower cutoff levels need to be utilized for protein-based markers, such as NMP22®, in order to enhance sensitivity for detecting small recurrent bladder tumors. However, at least one prospective randomized study reported that when a clinician knows the marker result, they detect and biopsy more tumors,132 and it remains unknown if this results in any clinical benefit or harm. Among other things, the new urine markers were aimed at specifically overcoming the low detection rate of urine cytology for low-grade tumors but this came at the expense of specificity. The previously discussed CxBladder Monitor™ was designed to detect recurrent bladder cancer in NMIBC patients on surveillance. Although this biomarker performed well for intermediate- and high-risk NMIBC patients in a large cohort study, its sensitivity was only 53% in a small subset of patients with an EORTC risk score of 0, which is equivalent to AUA low-risk.117 As such, there is currently insufficient evidence to recommend CxBladder Monitor™ during surveillance for low-risk patients. With the overall lack of combined effective specificity and sensitivity for low-risk patients, the Panel believes that current urinary biomarkers and cytology should not be routinely used for surveillance in these patients.