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. Cancer Epidemiol Biomarkers Prev; 19(5); 1193–200. ©2010 AACR.

©2010 American Association for Cancer Research.
2010
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