Case Studies

Prostate Cancer Gene 3 (PCA3) Assay

Making Better (Repeat) Prostate Biopsy Decisions

The Clinical Challenge

Prostate cancer (PCa) is one of the most common male cancers in the Western world.1 Currently, early detection of PCa relies primarily on an abnormal digital rectal examination (DRE) and an elevated prostate-specific antigen (PSA) level leading to a prostate biopsy. However, because of low positive predictive values, up to 75% of men with PSA values in the 2.5-10 ng/ml range and/or suspicious DRE have a negative first biopsy. Further, 10-35% of these men have PCa detected on repeat biopsy.2-3 In men with a negative first biopsy but persistent suspicion of PCa, a repeat biopsy is generally recommended. However, in approximately 80% of men, these repeat biopsies are negative. Not only economic aspects but also anxiety, discomfort, and sometimes severe complications are associated with prostate biopsies.2-3 Thus, there is a need for additional tests to increase the probability of detecting PCa at repeat biopsy and reduce the number of unnecessary biopsies. In this respect, the Prostate Cancer Gene 3 (PCA3) assay, a new PCa gene-based marker, has shown promising results.

Case Study

Patient History

Richard W., a 51-year-old executive was encouraged to have a screening prostate specific antigen (PSA) test by his brother who had been diagnosed with prostate cancer at the age of 46. Initial PSA determination revealed a level of 4.7 ng/mL. He was referred to a urologist who repeated the PSA which returned 4.9 ng/mL confirming the first measurement. Digital rectal examination showed moderate prostate enlargement without tenderness or palpable nodules. Transrectal ultrasound revealed a prostate volume of 42 cm3. Sextant biopsy demonstrated benign prostatic hyperplasia (BPH) without evidence of cancer.

Over the ensuing eight years, his PSA increased from 4.7 ng/mL to 12.1 ng/mL, while prostate volume increased from 42 cm3 to 58 cm3. During this period, abnormalities were noted in age-adjusted PSA, PSA density, and PSA velocity. Percentage free PSA remained in a mid-range throughout. He underwent 4 biopsies over the eight year period because of PSA abnormalities. Each biopsy demonstrated BPH, with no evidence of cancer. Late in the course of his surveillance, the PCA3 assay became available. The score was below the cut-off 35 (i.e., 10.1 and 5.0) on 2 separate occasions. Had the test been available early on, repeated biopsies might have been avoided and a degree of reassurance provided to the patient.

Patient Longitudinal Graph

Patient Longitudinal Graph

Value of PCA3 in the Prostate Biopsy Decision Process

The Prostate Cancer gene 3 (PCA3) assay is a new gene-based test. It is not a replacement for prostate specific antigen (PSA). It is an additional tool to help decide if in men suspected of having prostate cancer (PCa), e.g., those with a PSA between 2.5 and 10 ng/mL, prostate biopsy is really needed to diagnose PCa. PCA3 is, unlike PSA, prostate cancer specific. This means that it is only produced by PCa cells and not affected by prostate size. It discriminates better than PSA between PCa and benign/non-cancerous prostate diseases such as benign prostatic hyperplasia (BPH, i.e., prostate enlargement) or prostatitis (infection of the prostate). Therefore, PCA3 gives very useful information, in addition to PSA, in deciding if biopsy is really needed.

A high PCA3 Score indicates an increased likelihood of a positive biopsy, i.e., presence of cancer cells in the prostate. A low PCA3 score indicates a decreased likelihood of a positive biopsy. The greatest diagnostic utility occurs at a cut-off of 35.4


  1. Jemal A, Siegel R, Ward E, Murray T, Xu J and Thun MJ: Cancer statistics, 2007. CA Cancer J Clin. 57: 43-66, 2007.
  2. Seitz C, Palermo S and Djavan B: Prostate biopsy. Minerva Urol Nefrol. 55: 205-18, 2003.
  3. Raja J, Ramachandran N, Munneke G and Patel U: Current status of transrectal ultrasound-guided prostate biopsy in the diagnosis of prostate cancer. Clin Radiol. 61: 142-53, 2006.
  4. Deras IL, Aubin SM, Blase A, Day JR, Koo S, Partin AW, Ellis WJ, Marks LS, Fradet Y, Rittenhouse H et al.: PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol. 179: 1587-92, 2008.