PCA3: A Molecular Urine Assay for Predicting Prostate Biopsy Outcome

Deras, Ina L.; Aubin, Sheila M.J.; Blase, Amy; Day, John R.; Koo, Seongjoon; Partin, Alan W.; Ellis, William J.; Marks, Leonard S.; Fradet, Yves; Rittenhouse, Harry; Groskopf, Jack

doi:10.1016/j.juro.2007.11.038

« Previous Next »The Journal of Urology
Volume 179, Issue 4 , Pages 1587-1592, April 2008

PCA3: A Molecular Urine Assay for Predicting Prostate Biopsy Outcome

Ina L. Deras
- Gen-Probe, Inc., San Diego, California
- Equal study contribution.
- Financial interest and/or other relationship with Gen-Probe.
Sheila M.J. Aubin
- Gen-Probe, Inc., San Diego, California
- Equal study contribution.
- Financial interest and/or other relationship with Gen-Probe.
Amy Blase
- Gen-Probe, Inc., San Diego, California
- Financial interest and/or other relationship with Gen-Probe.
John R. Day
- Gen-Probe, Inc., San Diego, California
- Financial interest and/or other relationship with Gen-Probe.
Seongjoon Koo
- Gen-Probe, Inc., San Diego, California
- Financial interest and/or other relationship with Gen-Probe.
Alan W. Partin
- The Johns Hopkins Medical Institutions, Baltimore, Maryland
- Financial interest and/or other relationship with Gen-Probe.
William J. Ellis
- University of Washington, Seattle, Washington
- Financial interest and/or other relationship with Amgen, Medtronic and Onconome.
Leonard S. Marks
- Urological Sciences Research Foundation, Los Angeles, California
- Financial interest and/or other relationship with Allergan, American Medical Systems, Astellas, Bayer, Beckman Coulter, Diagnostic Ultrasound, GTX, GlaxoSmithKline, Gen-Probe, Light Science Oncology, Lilly ICOS, Merck, Novartis, Onconome, Pfizer, Sanofi, Solfay, Watson, National Institutes of Health Early Detection Research Network, Prostate Cancer Foundation CapCURE, Pardee Foundation and Seder Foundation.
Yves Fradet
- Diagnocure Inc. and Université Laval, Quebec City, Quebec, Canada
- Financial interest and/or other relationship with DiagnoCure, AstraZeneca and GlaxoSmithKline.
Harry Rittenhouse
- Gen-Probe, Inc., San Diego, California
- Financial interest and/or other relationship with Gen-Probe.
Jack Groskopf
- Gen-Probe, Inc., San Diego, California
- Financial interest and/or other relationship with Gen-Probe.
- Correspondence: Gen-Probe Inc., 10210 Genetic Center Dr., San Diego, California 92121 (telephone: 858-410-8850; FAX: 858-410-8302).

Received 3 July 2007 published online 22 February 2008.

Purpose

A urinary assay for PCA3, an mRNA that is highly over expressed in prostate cancer cells, has shown usefulness as a diagnostic test for this common malignancy. We further characterized PCA3 performance in different groups of men and determined whether the PCA3 score could synergize with other clinical information to predict biopsy outcome.

Materials and Methods

Prospectively urine was collected following standardized digital rectal examination in 570 men immediately before prostate biopsy. Urinary PCA3 mRNA levels were quantified and then normalized to the amount of prostate derived RNA to generate a PCA3 score.

Results

The percent of biopsy positive men identified increased directly with the PCA3 score. PCA3 assay performance was equivalent in the first vs previous negative biopsy groups with an area under the ROC curve of 0.70 and 0.68, respectively. Unlike serum prostate specific antigen the PCA3 score did not increase with prostate volume. PCA3 assay sensitivity and specificity were equivalent at serum prostate specific antigen less than 4, 4 to 10 and more than 10 ng/ml. A logistic regression algorithm using PCA3, serum prostate specific antigen, prostate volume and digital rectal examination result increased the AUC from 0.69 for PCA3 alone to 0.75 (p = 0.0002).

Conclusions

PCA3 is independent of prostate volume, serum prostate specific antigen level and the number of prior biopsies. The quantitative PCA3 score correlated with the probability of positive biopsy. Logistic regression results suggest that the PCA3 score could be incorporated into a nomogram for improved prediction of biopsy outcome. The results of this study provide further evidence that PCA3 is a useful adjunct to current methods for prostate cancer diagnosis.

Key Words: prostate, prostatic neoplasms, prostate cancer antigen 3, human, tumor markers, biological, diagnosis

Abbreviations and Acronyms: ASAP, atypical small acinar proliferation, BPH, benign prostatic hyperplasia, CaP, prostate cancer, DRE, digital rectal examination, LR, logistic regression, PCA3, prostate cancer gene 3, PIN, prostatic intraepithelial neoplasia, PSA, prostate specific antigen, PV, prostate volume