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Performance of PCA3 and TMPRSS2:ERG urinary biomarkers in prediction of biopsy outcome in the Canary Prostate Active Surveillance Study (PASS)

Prostate Cancer and Prostatic Diseases volume 22, pages 438–445 (2019)Cite this article

Subjects

Abstract

Background

For men on active surveillance for prostate cancer, biomarkers may improve prediction of reclassification to higher grade or volume cancer. This study examined the association of urinary PCA3 and TMPRSS2:ERG (T2:ERG) with biopsy-based reclassification.

Methods

Urine was collected at baseline, 6, 12, and 24 months in the multi-institutional Canary Prostate Active Surveillance Study (PASS), and PCA3 and T2:ERG levels were quantitated. Reclassification was an increase in Gleason score or ratio of biopsy cores with cancer to ≥34%. The association of biomarker scores, adjusted for common clinical variables, with short- and long-term reclassification was evaluated. Discriminatory capacity of models with clinical variables alone or with biomarkers was assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA).

Results

Seven hundred and eighty-two men contributed 2069 urine specimens. After adjusting for PSA, prostate size, and ratio of biopsy cores with cancer, PCA3 but not T2:ERG was associated with short-term reclassification at the first surveillance biopsy (OR = 1.3; 95% CI 1.0–1.7, p = 0.02). The addition of PCA3 to a model with clinical variables improved area under the curve from 0.743 to 0.753 and increased net benefit minimally. After adjusting for clinical variables, neither marker nor marker kinetics was associated with time to reclassification in subsequent biopsies.

Conclusions

PCA3 but not T2:ERG was associated with cancer reclassification in the first surveillance biopsy but has negligible improvement over clinical variables alone in ROC or DCA analyses. Neither marker was associated with reclassification in subsequent biopsies.

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Acknowledgements

The authors would like to thank the large and dedicated PASS team, including the coordinators and coordinating center staff. We also thank Scott Tomlins and Jack Groskopf for helpful comments and the research team at Hologic GenProbe for running the biomarker assays. Importantly, the authors also thank all of the men who have participated in PASS.

Funding

This work was supported by the Department of Defense Prostate Cancer Research Program (Grants W81XWH1110489 and W81XWH1410595), National Institutes of Health R01 CA181605, and Canary Foundation, Institute for Prostate Cancer Research.

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Authors and Affiliations

  1. Cancer Prevention Program, Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Lisa F. Newcomb & Daniel W. Lin

  2. Department of Urology, University of Washington, Seattle, WA, USA

    Lisa F. Newcomb & Daniel W. Lin

  3. Biostatistics Program, Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Yingye Zheng, Anna V. Faino & Marshall D. Brown

  4. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Daniella Bianchi-Frias & Peter S. Nelson

  5. Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA

    Matthew R. Cooperberg & Peter R. Carroll

  6. Department of Epidemiology & Biostatistics, University of California, San Francisco, CA, USA

    Matthew R. Cooperberg

  7. Department of Urology, Stanford University, Stanford, CA, USA

    James D. Brooks

  8. Department of Urology, VA Puget Sound Health Care System, Seattle, WA, USA

    Atreya Dash

  9. Department of Urology, Eastern Virginia Medical School, Virginia Beach, VA, USA

    Michael D. Fabrizio

  10. Department of Urologic Sciences, University of British Columbia, Vancouver, BC, USA

    Martin E. Gleave

  11. Department of Urology, University of Texas Health Sciences Center, San Antonio, TX, USA

    Michael Liss

  12. Department of Urology, University of Michigan, Ann Arbor, MI, USA

    Todd M. Morgan

  13. CHRISTUS Medical Center Hospital, San Antonio, TX, USA

    Ian M. Thompson

  14. Division of Urology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Andrew A. Wagner

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  1. Lisa F. Newcomb
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Corresponding authors

Correspondence to Peter S. Nelson or Daniel W. Lin.

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Newcomb, L.F., Zheng, Y., Faino, A.V. et al. Performance of PCA3 and TMPRSS2:ERG urinary biomarkers in prediction of biopsy outcome in the Canary Prostate Active Surveillance Study (PASS). Prostate Cancer Prostatic Dis 22, 438–445 (2019). https://doi.org/10.1038/s41391-018-0124-z

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