Bladder cancer is the sixth most common malignancy in Canada, and represents a significant diagnostic and management challenge. The incidence of bladder cancer is three times higher in men than in women and two times greater in Caucasian men than in Afro-American men. Smoking is a known risk factor.
At diagnosis, about 80% of bladder cancers are characterized as superficial tumors. Of these, transitional cell carcinoma (TCC) is the most common and has a high frequency of local recurrence and disease progression. The progression rate of TCC from superficial to muscle-invasive disease or metastasis ranges from 5% to 30%.

Since recurrence rates may be up to 70% at 5 years, surveillance and treatment of bladder cancer requires extensive and prolonged follow-up investigations.

Diagnosis
Current diagnosis and evaluation of bladder cancer is dependent upon use of cystoscopy and assessment of urine cytology. Direct visualization of the bladder mucosa by cystoscopy is the most efficient method for detecting primary and recurrent TCC of the bladder. However, it is invasive and has poor sensitivity in detection of low-grade tumors.

Cytological examination of urine has a high specificity for high grade bladder cancer but a low sensitivity for low grade tumours or dysplasia (11-17%). High-grade urothelial dysplasias are however, relatively easily detected.

Typically, both cystoscopy and cytology are used together with biopsy, when necessary, to optimize diagnostic sensitivity. Unfortunately, neither test alone nor combined is sufficient for early detection, assessment of recurrence or disease progression of bladder cancer.

More sensitive and non-invasive technologies are of particular interest to clinicians and patients. Methods based on the detection of soluble antigens shed by the tumors and voided in the urine are now commercially available.

NMP-22
The nuclear matrix proteins (NMP) play an important role in the structural framework of the nucleus and in DNA replication and gene expression. Significantly increased concentrations of NMP's have been found with neoplastic transformation and disease progression in carcinomas of the breast, colon and bladder. Soluble NMP's can be detected in the urine from bladder cancers using antibodies directed against select epitopes of NMP (NMP-22).

The specificity of NMP-22 for grade 1 TCC is 52% compared to 17% specificity for urine cytology and is therefore a more effective test to rule out low-grade TCC. The specificity for both urine cytology and NMP-22 in high grade tumours is excellent rendering both useful in the evaluation of these dysplasias. The sensitivity of NMP-22 has been noted to be generally higher than with cytology.

Risk stratification may also be possible using NMP-22: patients with a negative NMP-22 after tumor resection can be designated as low risk and may undergo a less rigorous protocol of cystoscopic surveillance.

Together with other clinically accepted tests and procedures, NMP-22 offers earlier detection in facilitating the diagnosis and management of bladder cancer.

Interpretation
Reference interval < 10 U/mL.

Indications for Testing
Post surgical monitoring and risk stratification in patients diagnosed with adjunct bladder cancer.
Adjunct tool for assessment of symptoms consistent with bladder cancer.
Advantages
Noninvasive.
Increased sensitivity for low-grade tumors.
Testing can be done as early as 5 days post-TURP surgery or cystoscopy.
Limitations
False positive results are associated with benign conditions such as interstitial cystitis and urinary tract infections.
Elevated NMP-22 levels may be observed immediately after rigorous exercise.
Catheterization may result in elevated values.
Test Availability
NMP-22 is currently available in Ontario and Alberta and will be available in Quebec as of April 2000. This test may not be insured by your provincial health plan but it may be covered by a patient's insurance plan.
Patient Preparation

Urine specimens may be collected at any time. No appointment is necessary.
Specimens must be stabilized immediately to avoid degradation by endogenous interference.
References
Miyanaga, N. et al. Eur. Urol. 31:163-168 (1997)
Zippe, C. et al. J. Urol. 161: 61-65 (1999)
Landman, J. et al. Urology 52 (3): 398-402 (1998)