Urine-based biomarkers for the early detection and surveillance of non-muscle invasive bladder cancer.

Bladder cancer has a very high frequency of recurrence and therefore requires lifelong surveillance, traditionally consisting of serial cystoscopy and cytology. These tests are both invasive and expensive, with considerable inter-user and inter-institutional variability. In addition, the sensitivity of cytology in detecting low-grade tumors is low. Therefore, there has been active investigation into urinary biomarkers that can either supplement or supplant these tests. At this point there are only six urine-based tests that are FDA-approved in bladder cancer surveillance, but a wide variety of other biomarkers are being studied. In this review, we examine the natural history of bladder cancer as well as the rationale and performance of an ideal urinary biomarker. The authors describe the FDA-approved biomarkers such as Bladder Tumor Antigen, ImmunoCyt, Nuclear Matrix Protein-22, and Fluorescent In Situ Hybridization, as well as the most promising investigational tests (i.e., Urinary bladder cancer test, BLCA-1, BLCA-4, hyaluronic acid, hyaluronidase, Lewis X antigen, microsatellite analysis, Quanticyt, soluble Fas, Survivin, and telomerase). The biological foundation, methodologies, and diagnostic performance of the biomarkers are discussed. The characteristics of the biomarkers are compared to urine cytology. At this time, urine biomarkers are utilized in a variety of clinical situations but their role is not well defined. The goal of identifying an optimal marker that will replace cystoscopy and/or cytology is still ongoing.

Screening for bladder cancer using urine-based tumor markers.

Bladder cancer screening differs from routine detection of bladder cancer in patients with symptoms, such as hematuria, or a history of bladder cancer. The ultimate goal of cancer screening is to decrease cancer-related mortality by detecting disease prior to the time that the disease would normally prompt evaluation from symptoms. There are several features of urothelial carcinoma of the bladder which make screening for this disease an attractive alternative to the current approach to this disease. The disease targets a defined population and survival for patients with this disease is strongly associated with disease stage at presentation. In addition, quick, easy, and painless screening tests are theoretically possible using tumor-related markers because of the direct exposure of cancer cells to urine. Indeed, recent insights into the biology of bladder cancer initiation and progression have resulted in the identification of several urine-based markers which have promise for detecting the presence of bladder cancer. Nevertheless, adoption of screening programs prior to establishing evidence of effectiveness and large-scale financial considerations has substantial damaging consequences. This article reviews the current literature regarding screening for bladder cancer using urine-based markers.