What are the urine tests for prostate cancer, specifically the PCA3 (Prostate Cancer Antigen 3) urine test?

Urine Tests for Prostate Cancer: PCA3 and Beyond

The PCA3 (Prostate Cancer Antigen 3) urine test is primarily recommended for men with previous negative prostate biopsies who have persistently elevated PSA levels, as it can help determine the need for repeat biopsies with high specificity. 1

PCA3 Test Overview

• PCA3 is a noncoding, prostate tissue-specific RNA that is significantly overexpressed in prostate cancer compared to normal prostate tissue or benign prostatic hyperplasia 1, 2
• The test involves collecting a urine sample after digital rectal examination (DRE) to quantify PCA3 overexpression 1
• FDA approval is specifically for men age 50 years or older with one or more previous negative prostate biopsies to help determine if a repeat biopsy is necessary 1

Clinical Performance of PCA3

• In the repeat biopsy setting, PCA3 has a negative predictive value (NPV) of 88% (95% CI, 81%-93%), meaning it could reduce unnecessary repeat biopsies by almost half 1
• Using a cutoff score of 35, PCA3 demonstrates a sensitivity of 52-67% and specificity of 64-87% for detecting prostate cancer 1, 3, 4
• PCA3 shows superior diagnostic accuracy compared to PSA alone, with area under the curve (AUC) values of 0.77 for PCA3 versus 0.57 for PSA in the same patient groups 4
• The risk of missing high-grade cancer with a low PCA3 score is approximately 3% in the repeat biopsy setting, but rises to 13% in the initial biopsy setting 1

Clinical Application Guidelines

• PCA3 is not recommended for initial prostate cancer screening due to the higher risk (13%) of missing high-grade disease in men without prior biopsy 1
• According to ESMO guidelines, in cases of elevated PSA and negative initial biopsies, a PCA3 test can be performed to determine whether re-biopsies are indicated 1
• The EGAPP Working Group found insufficient evidence to recommend PCA3 for determining if cancer is indolent or aggressive for treatment planning 1
• PCA3 scores correlate with cancer grade - patients with negative biopsies show lower PCA3 scores (mean=54.9) compared to patients with positive biopsies (mean=141.6) 5

Other Urine-Based Tests for Prostate Cancer

• The Prostate Health Index (phi) combines total PSA, free PSA, and proPSA to improve specificity in men with PSA between 4-10 ng/mL 1
• The 4Kscore test measures free and total PSA, human kallikrein 2, and intact PSA, along with clinical factors to predict high-grade cancer risk 1
• TMPRSS2:ERG fusion is another urine biomarker that has been studied for prostate cancer detection 1

Clinical Pitfalls and Considerations

• PCA3 should not be used as a standalone test but rather in conjunction with other clinical factors like DRE findings, prostate size, PSA levels, and prior biopsy history 1
• The most effective approach combines multiple biomarkers - a multivariable model containing PCA3, PSAD, PSA, DRE, and TRUS findings shows the highest diagnostic accuracy (AUC: 0.82) 3
• While PCA3 is useful for determining the need for repeat biopsies, it should not replace standard diagnostic procedures like prostate biopsy for definitive diagnosis 1
• The clinical utility of PCA3 is still evolving, with future applications potentially including its use in active surveillance protocols 6

Practical Implementation

• The PROGENSA PCA3 assay is the only FDA-approved test for PCA3 measurement 1
• The test reports a PCA3 score calculated as the ratio of PCA3 mRNA to PSA mRNA multiplied by 1000 5
• A PCA3 score cutoff of 35 is typically used to determine the need for repeat biopsy 1, 5
• The test has a high informative rate (99%) with valid score values obtainable in most patients 5