A Prospective, Multicenter, National Cancer Institute Early Detection Research Network Study of [−2]proPSA: Improving Prostate Cancer Detection and Correlating with Cancer Aggressiveness

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 19; no. 5; pp. 1193 - 1200
• Main Authors: Sokoll, Lori J., Sanda, Martin G., Feng, Ziding, Kagan, Jacob, Mizrahi, Isaac A., Broyles, Dennis L., Partin, Alan W., Srivastava, Sudhir, Thompson, Ian M., Wei, John T., Zhang, Zhen, Chan, Daniel W.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.05.2010
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Humans; Male; Medical sciences; Middle Aged; National Cancer Institute (U.S.); Neoplasm Staging; Nephrology. Urinary tract diseases; Prospective Studies; Prostate-Specific Antigen - blood; Prostatic Neoplasms - blood; Prostatic Neoplasms - diagnosis; ROC Curve; Tumors; Tumors of the urinary system; United States; Urinary tract. Prostate gland; United States; Urinary system disease; Prostate disease; Multicenter study; Malignancy; Malignant tumor; Prospective; Improvement; Cancerology; Scientific research; Network; Diagnosis; Detection; Male genital diseases; Prostate cancer; Cancer; Aggressiveness
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-10-0007

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.