Biomarkers In Prostate Cancer

Biomarker tests continue to impact the world of prostate cancer from early detection through diagnosis, by helping men to better understand their risk of having the disease and identifying the aggressiveness of the disease if present. A few of the most exciting biomarker tests for prostate cancer include:

• 4Kscore:The 4Kscore Test is a blood test that provides a patient-specific probability for finding a aggressive (Gleason score 7 or higher) prostate cancer upon biopsy. The information can be used by the Urologist to have an informed discussion with the patient about whether or not to have a prostate biopsy. The 4Kscore Test measures four prostate-specific kallikreins in the blood: Total PSA, Free PSA, Intact PSA, and Human Kallikrein 2 (hK2). The blood test results are combined in an algorithm with patient age, digital rectal exam (nodule, no nodule), and prior negative biopsy (yes, no). The 4Kscore Test then provides a % probability on a scales from <1% to >95% for the patient having aggressive prostate cancer.
• ProgensaPCA3: A FDA-approved urine test that detects the over-expression of a the PCA3 gene, which is specific to prostate cancer and an accurate predictor of whether cancer may be present.  The PCA3 score is used to determine if a repeat biopsy is needed in men who are used to determine a man’s PCA3 score, which indicates the need for biopsy. Research is underway looking at PCA3 as prostate cancer screening population as well.
• ERG Protein Tissue Marker:  Development of an ERG protein assays to be utilized on prostate cancer biopsy tissue is also underway.  Presence of the ERG protein in tissue helps to identify patients who have prostate cancer.  Additionally, the presence of ERG in high grade PIN (pre-cancerous lesion) is indicative of a patient more likely to be diagnosed with cancer upon the next biopsy.

Biomarkers will be increasingly valuable for patients and physicians in the decision making process.   Biomarkers in prostate cancer will one day help determine the best treatment option upon diagnosis. Prostate cancer comes in varying aggression levels, on which effective treatment is dependent. Emerging biomarkers include: 

TMPRSS2:ERG: This urine test under development helps to identify a subset of aggressive prostate cancers with high specificity and may play a role in monitoring the response to hormonal or other therapies in an individual patient. TMPRSS2:ERG gene fusions are prostate cancer specific DNA arrangements found in half of prostate cancers.

ERG Gene Tissue Marker: Development of ERG gene assays, which measures the fusion of TMPRSS2 to ERG, to be utilized on prostate cancer biopsy tissues is also underway.  This tissue assay will also help to identify prostate cancer aggressiveness and may lead to personalization of treatment options.   ERG rearrangement in prostate cancer at the time of diagnosis, are markers for predicting subsequent tumor behavior and can help in better predicting the clinical outcome.

ConfirmMDx: By analyzing genes associated with prostate cancer, this test helps to prevent prostate-cancer-free men, who have already received a biopsy, from undergoing an unnecessary repeat biopsy. The analysis is performed on remaining prostate tissues from a previously negative biopsy. It also helps to identify high-risk patients for further tests or treatment. 

InformMDx: This molecular prognostic test is still in its development phase, but will serve as a tool to distinguish between aggressive and non-aggressive tumors.

NADiA ProsVue: Used in conjunction with a clinical evaluation, the test can help identify patients at risk for recurrence of prostate cancer within an eight-year period following a prostatectomy. The test is an in-vitro diagnostic tool (takes place in a test tube), that determines the rate of change of serum tPSA (total PSA) over a period of time for further analysis.

Prostate Health Index (PHI): A simple blood test that is nearly 3 times more specific in detecting prostate cancer than PSA (prostate-specific antigen).  This test will help patients and physicians distinguish prostate cancer from benign conditions and help to prevent unnecessary prostate biopsies.

OncoType testing for prostate:  Currently under development, this biopsy-based, genomic assay is being researched to refine and individualize the risk assessment and treatment decision-making for men with localized prostate cancer.  This test is being evaluated to determine if a multi-gene test for patients with early stage prostate cancer can distinguish a more aggressive tumor, requiring immediate intervention, such as surgery or radiation, from a less aggressive disease that may be managed more conservatively with active surveillance.

Prolaris Diagnostic Test: This test predicts the survival rate of a man with prostate cancer within a 10-year period, based on RNA expression, and may help determine the best treatment approach for prostate cancer patients.

Phosphatase and tensin homolog (PTEN): Research on the PTEN gene is aimed at helping to reduce the likelihood of false-positive tests by distinguishing between localized prostate cancer and non-cancerous enlargement of the prostate. The PTEN gene is a four-protein signature that is commonly altered in men with prostate cancer. 

Emerging Biomarkers: RAF, BRAF, SPOP, EZH2, and Spink1 are biomarkers under analysis that provide great promise for future prostate cancer diagnosis, risk, aggressiveness and individualized treatment options.