The role of protein- and cell-based urinary biomarkers for bladder cancer detection and surveillance is controversial, and in 2017 these assays have yet to come into widespread use among urologists. Their uptake is expected to increase, however, considering that the American Urological Association/Society of Urologic Oncology “Guideline on Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer” (NMIBC) that was released in 2016 identifies situations for using urinary biomarkers, according to Badrinath R. Konety, MD.
According to the guideline, clinicians may use select urinary biomarkers to assess response to intravesical chemotherapy with bacillus Calmette-Guérin (UroVysion Bladder Cancer Kit) and to adjudicate equivocal cytology (UroVysion and ImmunoCyt). It also states, however, that urinary biomarkers should not be used in place of cystoscopic evaluation for surveillance of NMIBC. In addition, the guideline states that neither urinary biomarkers nor cytology should be routinely used during surveillance of a patient with a history of low-risk cancer and a normal cystoscopy.
Several urinary biomarkers have been approved by the FDA for use in bladder cancer detection and/or surveillance (table). These include fluorescence in situ hybridization (FISH [UroVysion]), nuclear matrix protein 22 (NMP22 [NMP22 and NMP22BladderChek]), bladder tumor antigen (BTA [BTA stat and BTA TRAK]), and fluorescent immunohistochemistry (ImmunoCyt/uCyt+).
Other urine-based tests marketed by clinical laboratories that meet Clinical Improvement Act standards include CertNDx and Cxbladder Triage, Cxbladder Detect, and Cxbladder Monitor. CertNDx assesses mutations in fibroblast growth factor receptor 3, which may be associated with lower grade bladder tumors that have a good prognosis, and is used in combination with cytology. The Cxbladder tests measure five genes (CDC2, HOXA13, MDK, AGFBP5, CXCR2). Cxbladder Triage also analyzes phenotypic and clinical risk factors and is intended for primary evaluation of patients with hematuria to reduce the need for an invasive workup in patients who have a low probability of having bladder cancer. Cxbladder Detect is intended for evaluation of patients presenting with hematuria as an adjunct to cystoscopy. Cxbladder Monitor combines the genomic biomarkers with patient-specific clinical factors and is used to monitor for bladder cancer recurrence.