Cancer of the bladder results in approximately 5000 deaths per year in the UK.

Worldwide, new cases and deaths in the year 2000 numbered 260,000 and 99,000 respectively. Risk rises steeply with age, with over half of all deaths occurring in patients aged 70 years or more. The incidence of bladder cancer is three to four times higher in men than women, and roughly twice as high in white men as black men. Cigarette smoking markedly increases the risk for bladder cancer - with nearly half of all new cases of bladder cancer occurring in current or former smokers. Occupational exposure to chemicals used in the dye, leather, tyre and rubber industries has also been associated with an increased risk of bladder cancer. Early detection and treatment may prevent progression to invasive disease or allow for more effective treatment of non-invasive tumours. Regular follow-up testing is required amongst patients treated for early stage bladder cancer because of the high risk of recurrent disease.

Haematuria, either gross or microscopic, is the most common sign of bladder cancer and traditionally has warranted a thorough investigation of the entire urinary tract. This usually comprises upper tract radiology, cystoscopy and urine cytology. Urine cytology is technically difficult, relatively expensive and has a low sensitivity for detecting small or low-grade tumours. Cystoscopy is painful, relatively expensive, and might fail to identify small tumour recurrences.

Limitations of traditional testing methods have lead researchers to investigate various markers in attempt to develop a simple, non-invasive, but precise, laboratory test.

NMP22 is a Nuclear Matrix Protein found in human epithelial cells. In the urine of healthy individuals, the protein is present in low levels (less 10 U/mL). Most patients with bladder cancer release large quantities of NMP22 into the urine. The NMP22 test quantifies levels of nuclear matrix protein called the nuclear mitotic apparatus protein (NuMA). Levels of NuMA in malignant tissue can be greater than 10 times the levels found in normal tissue. The NuMA antigen moiety detected by the NMP22 assay is referred to as NMP22.

NMP22 is the only bladder cancer marker with FDA approval (1996) as a monitoring tool to predict disease recurrence and was cleared in 2000 by the FDA for expanded use as a screening test for previously undiagnosed individuals who have symptoms of, or are at risk for, bladder cancer. It is also only the second tumour marker (in addition to prostate specific antigen (PSA) approved by the FDA and established in its laboratory format for screening and monitoring cancer patients. To date NMP22 is the most precise, has the most published studies and is the bladder cancer marker most widely used worldwide. It is approved for screening in Japan and China as well as the USA.

NMP22 is present in urine of healthy individuals at low levels. Patients with transitional cell carcinoma of the urinary tract have been shown to release greater levels of NMP22 into the urine than normal individuals. The quantitative values appear to be indicative of disease severity. Using a cut-off of 10 U/mL, NMP22 has a clinical sensitivity of approximately 70% for the detection of recurrent disease after surgical treatment. The negative predictive value has been shown to be greater than 80% in several studies.

False elevations may occur immediately after extreme exercise, in some benign urinary tract conditions and in patients undergoing systemic chemotherapy. Patients should not be tested with NMP22 if they have had a total cystectomy or if a cystoscopy has been undertaken within the last 5 days. An elevated result should not be interpreted as evidence of malignant disease in the urinary tract without confirmation using other diagnostic procedures.

In summary: Trials indicate that urinary NMP22 is a simple, non-invasive, cost-effective marker for the detection of bladder cancer. It will not replace cystoscopy but provides a more accurate diagnostic tool than cystoscopy and urine cytology.