Combinations of urine-based tumour markers in bladder cancer surveillance

Horstmann, Marcus; Patschan, Oliver; Hennenlotter, Jörg; Senger, Erika; Feil, G.; Stenzl, Arnulf

doi:10.3109/00365590903296837

Cited by 47 publications

(27 citation statements)

References 21 publications

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“…After removal of reviews, meta-analyses, and redundant trials, 20 studies assessable for criteria concerning assay performance and comprising more than 5,000 individuals were identified, forming the basis for this assessment of assay performance [13,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114]. …”

Section: Cell-based Assaysmentioning

confidence: 99%

Molecular Markers for Bladder Cancer Screening, Early Diagnosis, and Surveillance: The WHO/ICUD Consensus

et al. 2014

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Due to the lack of disease-specific symptoms, diagnosis and follow-up of bladder cancer has remained a challenge to the urologic community. Cystoscopy, commonly accepted as a gold standard for the detection of bladder cancer, is invasive and relatively expensive, while urine cytology is of limited value specifically in low-grade disease. Over the last decades, numerous molecular assays for the diagnosis of urothelial cancer have been developed and investigated with regard to their clinical use. However, although all of these assays have been shown to have superior sensitivity as compared to urine cytology, none of them has been included in clinical guidelines. The key reason for this situation is that none of the assays has been included into clinical decision-making so far. We reviewed the current status and performance of modern molecular urine tests following systematic analysis of the value and limitations of commercially available assays. Despite considerable advances in recent years, the authors feel that at this stage the added value of molecular markers for the diagnosis of urothelial tumors has not yet been identified. Current data suggest that some of these markers may have the potential to play a role in screening and surveillance of bladder cancer. Well-designed protocols and prospective, controlled trials will be needed to provide the basis to determine whether integration of molecular markers into clinical decision-making will be of value in the future.

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Section: Cell-based Assaysmentioning

confidence: 99%

Molecular Markers for Bladder Cancer Screening, Early Diagnosis, and Surveillance: The WHO/ICUD Consensus

et al. 2014

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“…An alternative option may be to explore serial measurements of urinary NMP22 concentration and determine its role in detecting recurrence, much like serum PSA in patients with prostate cancer. Finally, combinations of NMP22 and other tumour markers have been shown to increase the sensitivity and the NPV of NMP22 in the detection of recurrence of superficial urothelial tumours [19,20]. This stepwise approach of tumour marker determination may be useful in the future to reduce the frequency of surveillance cystoscopies at a reasonable risk, particularly in patients with low-grade superficial tumours [19].…”

Section: Discussionmentioning

confidence: 97%

Comparison of the sensitivity and specificity of urine cytology, urinary nuclear matrix protein-22 and multitarget fluorescence in situ hybridization assay in the detection of bladder cancer

Kehinde

Al-Mulla

Kapila

et al. 2010

Scandinavian Journal of Urology and Nephrology

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Objective. This study aimed to compare the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of urine cytology, BladderChek Ò nuclear matrix protein-22 (NMP22) and UroVysionÔ fluorescence in situ hybridization (FISH) tests in patients with newly diagnosed bladder cancer, those with recurrent bladder cancer, and those with bladder cancer but in remission during surveillance. Material and methods. Voided urine samples obtained from 178 patients with suspected or known bladder cancer about to undergo diagnostic or surveillance cystoscopy and 25 control subjects without the disease were divided into four and used for urine culture and cytology, NMP22 BladderChek and UroVysion FISH tests. The sensitivity, specificity, PPV and NPV for each test were calculated. Comparison was made between the ability of each test to detect bladder cancer in the three category of patients listed. Results. Of the 178 patients with bladder cancer, 43 were newly diagnosed, 58 had recurrent disease and 77 were in remission. The sensitivity of each test in newly diagnosed patients was: urine cytology 28%, NMP22 88% and FISH 80%; and in patients with recurrent disease: urine cytology 33%, NMP22 57% and FISH 85%. The mean specificity for urine cytology, NMP22 and FISH was 95%, 67% and 48%, respectively. Conclusion. Of the tests used in the study for detection of bladder cancer, NMP22 appeared to be most costeffective and rapid, with relatively high sensitivity and specificity in all categories of patients. The NMP22 test may be considered a new gold standard for the assessment of patients with known or suspected bladder cancer.

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“…Biofluids and tissues are collected from a group of patients of different cancer stages and compared with a group of healthy persons. The effect of cancer stage on sensitivity of a single biomarker should be taken into consideration as was pointed out in a recent study using four different bladder cancer markers (Table 3) [16]. The table shows that sensitivity improved with increase in cancer stage.…”

Section: Selection Of Patients and Controlsmentioning

confidence: 96%

“…Does a combination of biomarkers give better sensitivity and specificity? The answer is yes, for example, Horstmann et al [16] studied the effect of using a combination of bladder cancer biomarkers on sensitivity and specificity. Although none of the combinations resulted in 100% sensitivity and specificity, as shown in Table 1, the sensitivity improved over using Cyt, NMP22, immunocytology (uCyt1), or fluorescence in situ hybridization (FISH) separately ( Table 2).…”

Section: The Current State Of Biomarker Discoverymentioning

confidence: 99%

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Cancer biomarker discovery: Opportunities and pitfalls in analytical methods

2011

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Many diseases result in specific and characteristic changes in the chemical and biochemical profiles of biological fluids and tissues prior to development of clinical symptoms. These changes are often useful diagnostic and prognostic biomarkers. Identifying biomarkers that can be used for the early detection of cancer will result in more efficient treatments, reduction in suffering, and lower mortality rates. An ideal screening test should be non-invasive with high sensitivity and specificity. Proteomic and metabolomic analyses of biological samples can reveal changes in abundance levels of metabolites and proteins that when validated and confirmed through clinical trials can function as clinical tests for early detection, diagnosis, monitoring disease progression, and predicting therapeutic response. While the past decade has seen great advancements in proteomics and metabolomics research producing potential biomarkers for cancer, most of the identified biomarkers have failed to replace existing clinical tests. To become a clinically approved test, a potential biomarker should be confirmed and validated using hundreds of specimens and should be reproducible, specific, and sensitive. A search of the scientific and medical literature indicates that many studies report the discovery of potential biomarkers without proper validation and/or they do not meet the above criteria. In this manuscript, we will discuss the successes and the pitfalls of biomarker research and comment on study and experimental design, which in most cases is lacking, resulting in suboptimal biomarkers.

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Combinations of urine-based tumour markers in bladder cancer surveillance

Abstract: Combinations of tumour markers increased the sensitivity and NPV in the detection of recurrence of NMI TCC. A stepwise approach of tumour marker determination may be used to reduce the frequency of follow-up cystoscopies at a reasonable risk.

Cited by 47 publications

References 21 publications

Molecular Markers for Bladder Cancer Screening, Early Diagnosis, and Surveillance: The WHO/ICUD Consensus

Molecular Markers for Bladder Cancer Screening, Early Diagnosis, and Surveillance: The WHO/ICUD Consensus

Comparison of the sensitivity and specificity of urine cytology, urinary nuclear matrix protein-22 and multitarget fluorescence in situ hybridization assay in the detection of bladder cancer

Cancer biomarker discovery: Opportunities and pitfalls in analytical methods

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