Bladder tumor markers: from hematuria to molecular diagnostics--where do we stand?

Bladder cancer is a common malignancy in the USA. Currently, the detection of initial tumors and recurrent disease is based on evaluation of voided urinary specimens, often followed by cystoscopy. With the high rate of recurrence, cystoscopies are regularly repeated with the aim of halting progression of the disease. For patients, this process is fraught with anxiety, pain and high cost. As a result, intense work is being done in the field of bladder tumor markers with the goal of identifying bladder cancer earlier, both in the initial diagnosis and in recurrences of known tumor. The possibility of identifying a marker that could noninvasively differentiate benign and malignant causes of hematuria, and identify recurrences prior to their pathologic progression is the objective of this area of research. Currently, a large number of tumor markers exist, each scrutinized in both the laboratory and in clinical trials. Here we present many of the most widely used and tested markers. Background details are provided as to the mechanism of detection of malignant cells, the results of recent trials and future directions of study. Some novel modalities for tumor detection are also presented. The next few years will no doubt bring newer markers and lead to the elimination of others. Studies continue to refine the role of these markers in clinical practice, but their ultimate efficacy will need to be borne out in large-scale clinical trials in a multitude of settings.