A prospective, multicenter, national cancer institute early detection research network study of [-2]proPSA: Improving prostate cancer detection and correlating with cancer aggressiveness

Lori J. Sokoll, Martin G. Sanda, Ziding Feng, Jacob Kagan, Isaac A. Mizrahi, Dennis L. Broyles, Alan W. Partin, Sudhir Srivastava, Ian M. Thompson, John T. Wei, Zhen Zhang, Daniel W. Chan

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

Abstract

Background: The free prostate-specific antigen (PSA) isoform, [-2]proPSA, has been shown to be associated with prostate cancer. The study objective was to characterize the clinical utility of serum [-2]proPSA for prostate cancer detection and assess its association with aggressive disease. Methods: From among 669 subjects in a prospective prostate cancer detection study at four National Cancer Institute Early Detection Research Network clinical validation centers, 566 were eligible. Serum PSA, free PSA, and [-2]proPSA were measured (Beckman Coulter Access 2 Analyzer). Results: Two hundred and forty-five (43%) of the 566 participants had prostate cancer on biopsy. At 70% specificity, the sensitivity of %[-2]proPSA ([-2]proPSA/fPSA) was 54% [95% confidence interval (CI), 48-61%; null hypothesis, 40%]. Including %[-2]proPSA in a multivariate prediction model incorporating PSA and %fPSA improved the performance (P < 0.01). In the 2 to 4 ng/mL PSA range, %[-2]proPSA outperformed %fPSA (receiver operator characteristic-areas under the curve, 0.73 versus 0.61; P = 0.01). At 80% sensitivity, %[-2]proPSA had significantly higher specificity (51.6%; 95% CI, 41.2-61.8%) than PSA (29.9%; 95% CI, 21.0-40.0%) and %fPSA (28.9%; 95% CI, 20.1-39.0%). In the 2 to 10 ng/mL PSA range, a multivariate model had significant improvement (area under the curve, 0.76) over individual PSA forms (P < 0.01 to <0.0001). At 80% sensitivity, the specificity of %[-2]proPSA (44.9%; 95% CI, 38.4-51.5%) was significantly higher than PSA (30.8%; 95% CI, 24.9-37.1%) and relatively higher than %fPSA (34.6%; 95% CI, 28.5-41.4%). %[-2]proPSA increased with increasing Gleason score (P < 0.001) and was higher in aggressive cancers (P = 0.03). Conclusions: In this prospective study, %[-2]proPSA showed potential clinical utility for improving prostate cancer detection and was related to the risk of aggressive disease. Impact: The addition of %[-2]proPSA could affect the early detection of prostate cancer.

Original languageEnglish (US)
Pages (from-to)1193-1200
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume19
Issue number5
DOIs
StatePublished - May 2010

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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