Prostate-specific antigen (PSA) has long been the cornerstone biomarker for assessing prostatic disease, particularly prostate cancer. However, the limitations of PSA testing, including its lack of specificity and potential for overdiagnosis and overtreatment, have spurred the search for alternative laboratory tests to complement or supplement PSA in the evaluation of prostatic disease. 

1. Prostate Health Index (phi):

The Prostate Health Index (phi) is a blood test that combines three PSA isoforms—total PSA, free PSA, and [-2]proPSA—to improve the specificity of PSA testing. By calculating a phi score based on the ratio of these PSA isoforms, phi aims to distinguish between benign prostatic conditions and prostate cancer more accurately than PSA alone. Studies have shown that phi outperforms traditional PSA testing in discriminating between benign prostatic hyperplasia (BPH) and prostate cancer, as well as in predicting the presence of high-grade tumors.

2. 4Kscore Test:

The 4Kscore Test is a blood test that measures the levels of four kallikrein proteins—total PSA, free PSA, intact PSA, and human kallikrein-related peptidase 2 (hK2)—to assess the risk of aggressive prostate cancer. By combining these biomarkers with clinical information such as age, digital rectal examination findings, and prior prostate biopsy results, the 4Kscore Test provides a personalized risk assessment for aggressive prostate cancer. It helps clinicians identify patients who may benefit from further diagnostic evaluation, such as prostate biopsy, while sparing those at low risk from unnecessary invasive procedures.

3. SelectMDx Test:

The SelectMDx Test is a urine-based test that detects RNA biomarkers associated with prostate cancer aggressiveness. By analyzing the expression levels of these biomarkers, SelectMDx stratifies patients into low or high risk for clinically significant prostate cancer, helping to guide the decision-making process regarding prostate biopsy. Studies have shown that SelectMDx has high sensitivity for detecting aggressive prostate cancer, with a low false-positive rate, potentially reducing the number of unnecessary biopsies and associated complications.

4. PCA3 Test:

The Prostate Cancer Antigen 3 (PCA3) Test is a urine-based test that measures the expression of the PCA3 gene, which is overexpressed in prostate cancer cells. PCA3 testing aims to improve the specificity of prostate cancer detection compared to PSA by targeting a cancer-specific biomarker. While PCA3 testing has shown promise in distinguishing between benign and malignant prostate conditions, its role in clinical practice remains somewhat limited, and further research is needed to validate its utility as a standalone test or in combination with other biomarkers.