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Screening for bladder cancer with urinary tumor markers in chemical workers with exposure to aromatic amines

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Abstract

Purpose

To validate urinary markers for the early detection of bladder cancer (BC) in chemical workers.

Methods

UroScreen was conducted as a validation study for tumor markers within the frame of a health surveillance program of the German Social Accident Insurance for active or retired workers with former exposure to aromatic amines. From 2003 to 2010, 1,609 men took part in voluntary annual screens. Cytology, the quantitative NMP22® assay, and UroVysion™ were applied to 7,091 urine samples.

Results

Fifteen out of 21 tumors were detected following test positivity. The UroVysion/NMP22 panel detected 14 out of 21 tumors versus 8 tumors with cytology alone (sensitivity 66.7 vs. 44.4 %, specificity 94.5 vs. 98.5 %). The sensitivity of the panel increased to 85.7 % in samples collected ≤12 months before diagnosis and when papillomas were excluded, compared to 58.3 % with cytology. About 3 % of NMP22 tests were false-positive. UroVysion results overlapped with cytology due to the preselection of atypical cells. NMP22 was less and UroVysion more frequently positive in diluted urine samples. Leukocytes confounded NMP22 but not UroVysion. The low incidence of BC in this study population yielded low positive predictive values of the markers and high costs per tumor detected with screening.

Conclusions

UroVysion in combination with NMP22 detected more cases than cytology alone, at the expense of a lower specificity. High costs per detected case resulted from a lower BC incidence than in the past when levels of occupational exposure to aromatic amines were higher. Currently, it cannot be recommended to apply these markers for screening in asymptomatic workers. The increase in sensitivity is not balanced by the high costs of UroVysion and the false-positive tests of NMP22.

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Acknowledgments

We thank Friedhelm Eberle for the careful execution and documentation of the urinalyses. This unique database allowed the exploration of the influence of the urine status on the tumor tests.

Conflict of interest

The study received a Grant (FB093) from the German Social Accident Insurance (DGUV), Sankt Augustin, Germany. A.S. received free assay kits from Abbott Laboratories and Matritech/Alere Ltd. G.J. received free assay reagents from Fujirebio Diagnostics, Inc. M.K. and H.W. are employees of the sponsor. Y.L. does research with Abbott Laboratories and Matritech/Alere Ltd.

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Authors and Affiliations

  1. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Buerkle-de-la-Camp-Platz 1, 44789, Bochum, Germany

    Beate Pesch, Dirk Taeger, Georg Johnen, Katarzyna Gawrych, Nadine Bonberg, Matthias Kluckert & Thomas Brüning

  2. Protein Research Unit Ruhr within Europe (PURE), Ruhr University of Bochum, Bochum, Germany

    Nadine Bonberg

  3. Institute of Urology, Eberhard Karls University, Tübingen, Germany

    Christian Schwentner & Arnulf Stenzl

  4. German Social Accident Insurance’s Institution for the Raw Materials and Chemical Industry (BG RCI), Heidelberg, Germany

    Harald Wellhäußer & Matthias Kluckert

  5. Department of Health Protection and Occupational Safety, Currenta GmbH & Co. OHG, Leverkusen, Germany

    Gabriele Leng

  6. Occupational Medicine and Health Protection, BASF SE, Ludwigshafen, Germany

    Michael Nasterlack

  7. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Yair Lotan

Authors
  1. Beate Pesch
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  2. Dirk Taeger
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the UroScreen Study Group

Corresponding author

Correspondence to Beate Pesch.

Additional information

Beate Pesch and Dirk Taeger have equally contributed to this article.

Please refer the “Appendix” section for UroScreen Study Group.

Appendix

Appendix

UroScreen Study Group

BASF SE, Department of Occupational Medicine and Health Protection, Ludwigshafen: Bernd Scheuermann, Friedhelm Eberle, Thomas Mayer, Michael Nasterlack.

BG RCI, Bereich Prävention, Heidelberg: Harald Wellhäußer, Matthias Kluckert; Organisationsdienst für nachgehende Untersuchungen (ODIN): Reinhard Detzner.

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of Ruhr-Universität Bochum (IPA), Bochum: Dirk Taeger, Beate Pesch, Katarzyna Gawrych, Heike Bontrup, Georg Johnen, Nadine Bonberg, Judith Delbanco, Evelyn Heinze, Thomas Brüning.

Protein Research Unit Ruhr within Europe (PURE), Ruhr University of Bochum: Nadine Bonberg.

Currenta GmbH & Co. OHG, Safety—Health Protection, Leverkusen: Gabriele Leng.

Institute of Urology, Eberhard Karls University, Tübingen: Gerhard Feil, Karl-Dietrich Sievert, Séverine Banek, Christian Schwentner, Margarete Geiger, Erika Senger, Valentina Gerber, Andrea Hohneder, Gundi Beger, Ursula Kuehs, Jörg Hennenlotter, Arnulf Stenzl.

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Pesch, B., Taeger, D., Johnen, G. et al. Screening for bladder cancer with urinary tumor markers in chemical workers with exposure to aromatic amines. Int Arch Occup Environ Health 87, 715–724 (2014). https://doi.org/10.1007/s00420-013-0916-3

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  • DOI: https://doi.org/10.1007/s00420-013-0916-3

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