The role of haematuria in bladder cancer screening among men with former occupational exposure to aromatic amines

Pesch, Beate; Nasterlack, Michael; Eberle, Friedhelm; Bonberg, Nadine; Taeger, Dirk; Leng, G.; Feil, G.; Johnen, Georg; Ickstadt, Katta; Kluckert, Mattias; Wellhäußer, Harald; Stenzl, A; Brüning, Thomas

doi:10.1111/j.1464-410x.2010.09971.x

Cited by 42 publications

(27 citation statements)

References 23 publications

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“…fire fighters, chemical workers, and workers in alloy smelters) [133,135,136] using NMP22, uCyt+, or a mix of different molecular markers demonstrated good sensitivity and specificity for the markers. However, due to the low prevalence of disease (≤1%) in the cohorts studied, the PPV of the assays remains unsatisfactory.…”

Section: Screeningmentioning

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: Screeningmentioning

confidence: 99%

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

et al. 2014

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“…In terms of confounding, survivin was less influenced than NMP22 and UroVysion by urine status [36], [37]. According to the GEE model, creatinine and leukocytes did not influence the test results for survivin.…”

Section: Discussionmentioning

confidence: 83%

“…They were examined between September 2003 and June 2010. Urine samples were collected for urine status, cytology, the determination of NMP22®, chromosomal aberrations (UroVysion™), and – if sufficient material was available – for survivin [36], [37]. For survivin measurements 5,716 urine samples could be obtained from 1,540 participants (Tables 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

“…UroScreen was a prospective cohort study with more than 1,500 chemical workers aimed to assess NMP22, UroVysion, and survivin as tumor markers [36], [37]. It was the first prospective study that investigated the performance of survivin in the early detection of bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

“…In all samples the urine status was determined in fresh urine (before centrifugation) as described previously [36]. Urinary creatinine was determined with the CREA plus® test (Roche Diagnostics, Mannheim, Germany).…”

Section: Methodsmentioning

confidence: 99%

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Performance of Survivin mRNA as a Biomarker for Bladder Cancer in the Prospective Study UroScreen

et al. 2012

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BackgroundUrinary biomarkers have the potential to improve the early detection of bladder cancer. Most of the various known markers, however, have only been evaluated in studies with cross-sectional design. For proper validation a longitudinal design would be preferable. We used the prospective study UroScreen to evaluate survivin, a potential biomarker that has multiple functions in carcinogenesis.Methods/ResultsSurvivin was analyzed in 5,716 urine samples from 1,540 chemical workers previously exposed to aromatic amines. The workers participated in a surveillance program with yearly examinations between 2003 and 2010. RNA was extracted from urinary cells and survivin was determined by Real-Time PCR. During the study, 19 bladder tumors were detected. Multivariate generalized estimation equation (GEE) models showed that β-actin, representing RNA yield and quality, had the strongest influence on survivin positivity. Inflammation, hematuria and smoking did not confound the results. Survivin had a sensitivity of 21.1% for all and 36.4% for high-grade tumors. Specificity was 97.5%, the positive predictive value (PPV) 9.5%, and the negative predictive value (NPV) 99.0%.ConclusionsIn this prospective and so far largest study on survivin, the marker showed a good NPV and specificity but a low PPV and sensitivity. This was partly due to the low number of cases, which limits the validity of the results. Compliance, urine quality, problems with the assay, and mRNA stability influenced the performance of survivin. However, most issues could be addressed with a more reliable assay in the future. One important finding is that survivin was not influenced by confounders like inflammation and exhibited a relatively low number of false-positives. Therefore, despite the low sensitivity, survivin may still be considered as a component of a multimarker panel.

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Noninvasive diagnosis of urothelial cancer in urine using DNA hypermethylation signatures—Gender matters

Köhler

Bonberg

Ahrens

et al. 2019

Intl Journal of Cancer

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Urothelial cancer (UCa) is the most predominant cancer of the urinary tract and noninvasive diagnosis using hypermethylation signatures in urinary cells is promising. Here, we assess gender differences in a newly identified set of methylation biomarkers. UCa‐associated hypermethylated sites were identified in urine of a male screening cohort (n = 24) applying Infinium‐450K‐methylation arrays and verified in two separate mixed‐gender study groups (n = 617 in total) using mass spectrometry as an independent technique. Additionally, tissue samples (n = 56) of mixed‐gender UCa and urological controls (UCt) were analyzed. The hypermethylation signature of UCa in urine was specific and sensitive across all stages and grades of UCa and independent on hematuria. Individual CpG sensitivities reached up to 81.3% at 95% specificity. Albeit similar methylation differences in tissue of both genders, differences were less pronounced in urine from women, most likely due to the frequent presence of squamous epithelial cells and leukocytes. Increased repression of methylation levels was observed at leukocyte counts ≥500/μl urine which was apparent in 30% of female and 7% of male UCa cases, further confirming the significance of the relative amounts of cancerous and noncancerous cells in urine. Our study shows that gender difference is a most relevant issue when evaluating the performance of urinary biomarkers in cancer diagnostics. In case of UCa, the clinical benefits of methylation signatures to male patients may outweigh those in females due to the general composition of women's urine. Accordingly, these markers offer a diagnostic option specifically in males to decrease the number of invasive cystoscopies.

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The role of haematuria in bladder cancer screening among men with former occupational exposure to aromatic amines

Cited by 42 publications

References 23 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

Performance of Survivin mRNA as a Biomarker for Bladder Cancer in the Prospective Study UroScreen

Noninvasive diagnosis of urothelial cancer in urine using DNA hypermethylation signatures—Gender matters

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