Elsevier

Urology

Volume 69, Issue 3, March 2007, Pages 532-535
Urology

Adult urology
PCA3 Molecular Urine Assay for Prostate Cancer in Men Undergoing Repeat Biopsy

This work was presented in part at the Annual Meeting of the American Urological Association, Atlanta, Georgia, May 2006.
https://doi.org/10.1016/j.urology.2006.12.014Get rights and content

Objectives

Men with elevated serum prostate-specific antigen (PSA) levels and negative prostate biopsy findings present a dilemma because of the lack of an accurate diagnostic test. We evaluated the potential utility of the investigational prostate cancer gene 3 (PCA3) urine assay to predict the repeat biopsy outcome.

Methods

Urine was collected after digital rectal examination (three strokes per lobe) from 233 men with serum PSA levels persistently 2.5 ng/mL or greater and at least one previous negative biopsy. The specimens were collected from April 2004 to January 2006. The PCA3 scores were determined using a highly sensitive quantitative assay with transcription-mediated amplification. The ability of the PCA3 score to predict the biopsy outcome was assessed and compared with the serum PSA levels.

Results

The RNA yield was adequate for analysis in the urine samples from 226 of 233 men (ie, the informative specimen rate was 97%). Repeat biopsy revealed prostate cancer in 60 (27%) of the of 226 remaining subjects. Receiver operating characteristic curve analysis yielded an area under the curve of 0.68 for the PCA3 score. In contrast, the area under the curve for serum PSA was 0.52. Using a PCA3 score cutoff of 35, the assay sensitivity was 58% and specificity 72%, with an odds ratio of 3.6. At PCA3 scores of less than 5, only 12% of men had prostate cancer on repeat biopsy; at PCA3 scores greater than 100, the risk of positive biopsy was 50%.

Conclusions

In men undergoing repeat prostate biopsy to rule out cancer, the urinary PCA3 score was superior to serum PSA determination for predicting the biopsy outcome. The high specificity and informative rate suggest that the PCA3 assay could have an important role in prostate cancer diagnosis.

Section snippets

Material and Methods

The urine samples were obtained from three North American sites: Laval University (Quebec City, Quebec, Canada), Urological Sciences Research Foundation (Los Angeles, Calif), and the University of Washington School of Medicine (Seattle, Wash). The respective institutional review boards approved the study protocol, and all study subjects provided written informed consent. The specimens were collected from April 2004 to January 2006.

The study population consisted of 233 consecutive men with serum

Results

For the subject group studied, 226 of 233 specimens yielded sufficient RNA for analysis, corresponding to an informative specimen rate of 97%. For the 226 subjects with informative specimens, 60 repeat biopsies were positive for CaP and 166 were negative. All CaP cases found were Gleason grade 6 (65%) or 7 (35%).

To assess the ability of the PCA3 assay to predict the prostate biopsy outcome, receiver operating characteristic (ROC) curve analysis was performed using the biopsy result as the

Comment

CaP will have been diagnosed in approximately 230,000 U.S. men during 2006.12 The great majority of these men will have undergone prostate biopsy because of an elevated serum PSA level. The positive predictive value of a serum PSA level of 4.0 ng/mL or more, the biopsy trigger currently recommended by the American Urological Association,13 is approximately 24% for men in their seventh decade.14 Thus, about 1 million U.S. men will have undergone a prostate biopsy in 2006 to detect CaP in one

Conclusions

PCA3 gene overexpression is detectable in urine, providing the basis for a specific CaP test. Improved PCA3 assay methods—applied in this study in 233 men with serum PSA levels greater than 2.5 ng/mL and previous negative biopsy findings—allowed for the prediction of CaP on repeat biopsy with a specificity of 72%, sensitivity of 58%, and an odds ratio of 3.6, using a PCA3 score cutpoint of 35 (copies of PCA3 per copy of PSA mRNA). The risk of positive biopsy findings correlated with the

Acknowledgment

To Seongjoon Koo, Art Weber, and James Tatlow for help in trial management and data analysis, and Dr. Robert Vessella for help and guidance with specimen collection, study design, and data analysis.

References (15)

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Cited by (0)

1

W. J. Ellis has served as a speaker, paid consultant, and study investigator for Gen-Probe.

2

Y. Fradet has served as a speaker, paid consultant, and study investigator for Gen-Probe and DiagnoCure.

3

L. S. Marks has served as a speaker, paid consultant, and study investigator for Gen-Probe and Beckman-Coulter, Inc.

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