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Bladder Cancer
Advances in the Understanding of the Early Detection of Bladder Cancer
a report by
Levent N Türkeri
1
and Ilker Tinay
2
1. Professor of Urology; 2. Consultant, Department of Urology, Marmara University School of Medicine
Bladder cancer is a major health problem across the world, mainly due Nuclear Matrix Protein Assay
to its association with tobacco abuse. A final diagnosis is achieved The NMP22
®
test uses nuclear matrix protein (NMP22), a specific nuclear
through cystoscopy and resection of tumours for pathological protein that is responsible for the chromatid regulation and cell separation
examination. Detection of recurrent disease is based on cystoscopic during replication in voided urine.
9
Two NMP22 tests are available for daily
follow-up as well as urine-related examinations. As the risk of disease practice. The original NMP22 bladder cancer test (BCT) is a quantitative
recurrence requires quite frequent endoscopic surveillance, follow-up immunoassay and the NMP22 BladderCheck is a qualitative point-of-care
is hampered by patient anxiety and discomfort, accompanied by a high test cartridge containing the NMP22 detecting and reporter antibodies.
number of cystoscopies either at the office or in the hospital;
furthermore, cost is a factor. Therefore, the high number of Ponsky et al. identified conditions associated with false-positive NMP22
endoscopic interventions makes bladder cancer one of the most costly results and concluded that benign inflammatory or infectious conditions,
of all tumours in both the US and Europe.
1–3
Thus, the availability of a presence of renal or bladder calculi, history of foreign body in the urinary
tumour marker that may help to discover the presence of a tumour in tract, any bowel interposition segment, another genito-urinary cancer and
the bladder either initially or during follow-up would be extremely an instrumented urinary sample should be applied as exclusion criteria to
useful. Currently, many markers are under evaluation; the following increase the positive predictive value (PPV) and specificity of the NMP22
article focuses on some of the most relevant. assay.
10
In a recent review, sensitivity ranges for the NMP22 BCT and
BladderCheck assays were reported as 34.6–100% and 49.5–65% and
Blood Tumour Antigen Assays specificity as 60–95% and 40–89.8%, respectively.
8
The area under the
The original Bard
®
bladder tumour antigen (BTA) test is a latex receiver operating characteristic (AUROC) curve for bladder transitional cell
agglutination assay that detects basement membrane degradation carcinoma (TCC) detection was 0.735 (95% confidence interval [CI]
complexes. Various BTA tests, i.e. the Bard BTA, BTA-stat and BTA- 0.715–0.755, range across various institutions 0.676–0.889). The
TRAK, are available for clinical practice.
4
Of the two derivatives of the manufacturer-recommended cut-off of 10U/ml detected 57% of cases with
BTA test, the BTA-stat is a qualitative assay that can be performed in a a 19% false-positive rate. Area under the curve (AUC) for grade III and stage
few minutes, even before cystoscopy, and the BTA-TRAK is a T2 or greater disease was 0.806 (95% CI 0.780–831) and 0.864 (95% CI
quantitative two-step enzyme-linked immunosorbent assay (ELISA). 0.839–0.890), respectively. For each NMP22 cut-off, NMP22 had higher
They both measure the human complement factor-H-related protein in sensitivity for detecting grade III and stage T2 or greater bladder transitional
urine. The Finnbladder Group reported conditions that may cause cell carcinoma than for detecting any cancer. No optimal cut-offs for
false-positive BTA-stat results as previous or ongoing bladder detecting any or aggressive bladder transitional cell carcinoma could be
instillation treatment, urinary infection and urinary tract stone derived based on NMP22 values.
11
More recently, 94 consecutive urine
disease.
5
These reasons may give false-positive results in over 25% of cytology samples of bladder urothelial cancer, NMP22 testing and
cases.
6
A comparison study between these two BTA tests has shown a cystoscopy with surgical biopsy were obtained in a study to determine the
slightly superior sensitivity rate (77.6 versus 65.3%) for the BTA-TRAK efficacy and utility of NMP22 in follow-up of bladder urothelial carcinoma
test.
7
In a recent review, sensitivity ranges for the BTA-stat and BTA- (UC) and to compare NMP22 as a single evaluating test versus combination
TRAK were reported as 52.5–78% and 51–100% and specificity with cytology.
12
NMP22 specificity was 100%, sensitivity 45%, PPV 100%
ranges as 69–87.1% and 73–92.5%, respectively.
8
and negative predictive value (NPV) 87%. NMP22 showed lower sensitivity
for high-grade lesions and higher for low-grade lesions. When regarded as
positive, cytology resulted in 75% sensitivity, 58% specificity, 33% PPV and
Levent N Türkeri is a Professor of Urology in the
Department of Urology at Marmara University School of
89% NPV. NMP22 correctly classified 60% of false-negative cases
Medicine and Director of the Ergun Özalp Basic Research
diagnosed by cytology with low-grade UC and clarified 27 inconclusive
Laboratory at the same university. He serves as a Board
cytological diagnoses. Combined interpretation showed 90% sensitivity,
Member of the European Society of Oncological Urology
(ESOU), and is a member of the International Urological
92% specificity, 75% PPV and 98% NPV. Thus, it was concluded that
Society (SIU), the American Urological Association (AUA),
combined interpretation of NMP22 and cytology shows promise as an
the European Association of Urology (EAU), the Society
for Basic Urological Research (SBUR) and the European
effective, non-invasive method for surveillance of UC.
School of Urology (ESU), among others. Professor Türkeri has earned numerous awards,
including the Prize of the President from the XIII Congress of European Association of
Bladder Tumour Antigen and Nuclear Matrix Protein
Urology for Outstanding Contribution to Urological Oncology in 1994.
Assays Compared with Cytology
E:
turkeri@marmara.edu.tr
Compared with the other urine markers, the BTA-stat and the NMP22
tests have been extensively studied and compared with cytology. For pTa
28 © TOUCH BRIEFINGS 2008
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