Prostate Cancer Biomarkers

Biomarkers are measurable indicators of cancer risk, diagnosis, prognosis or targeted therapies (theranostics). This may involve detecting changes in your genetic material or that of the tumor, in proteins or other biomolecules that can be tested for in your blood or bodily fluids. (e.g. saliva, urine or stool). Generally speaking, biomarkers can be used for cancer screening, diagnosis, therapeutic strategy, as well as predicting and monitoring treatment responses.

Ideally, prostate cancer biomarkers for early diagnosis or screening will detect cases of prostate cancer easily (high sensitivity), and have minimal risk of false positives (high specificity).

While the most used biomarker test, the prostate-specific antigen (PSA) test, is highly sensitive in detecting prostate cancer — it still has a high risk of false positives. For some patients, doctors may still wish to use other tests before recommending a prostate biopsy, the final step necessary for a confirmatory diagnosis.

New medical imaging techniques such as multiparametric magnetic resonance imaging (mpMRI) have now been shown to be effective in helping to decide whether a biopsy is necessary if the PSA test suspects prostate cancer.

But in around 30% of cases, mpMRI is still unable to rule out or confirm the suspicion of prostate cancer. Subsequently, researchers set out to find reliable, affordable methods that would be easy to use in the clinic and would enable highly suspicious cases of prostate cancer to be accurately identified and selected for prostate biopsy.

If successful, these new biomarkers can serve as a preliminary alternative to prostate biopsy when mpMRI is insufficient to make a decision. They can help to reduce anxiety, bleeding and risk of hospitalization associated with unnecessary prostate biopsies.

According to the US National Comprehensive Cancer Network (NCCN), the chances of intermediate to high-risk prostate cancer (e.g. Gleason score with majority of grade 4 or higher) can be better established by blood tests such as the Prostate Health Index (PHI), 4Kscore or urine tests such as SelectMDx and ExoDx Prostate Test.

• Prostate Health Index (PHI)

The PHI test is an FDA-approved test that predicts how useful a biopsy would be for you, by predicting how likely it would be to find prostate cancer.

The test relies on measuring three different forms of PSA in your blood: p2PSA (an inactive and shortened precursor of PSA), free PSA (PSA that floats freely in your blood), and total PSA (includes free PSA and PSA bound to other proteins in your blood).

Currently, it is the most affordable (estimated at USD $80) of available alternative biomarker tests, beyond the usual PSA test.

• 4Kscore

The 4Kscore is another FDA-approved test that can help predict the risk of aggressive prostate cancer. It does so by identifying four kallikreins, a family of proteins which include the PSA (kallikrein-3) commonly associated with prostate cancer.

These bring together different forms of the PSA: total PSA, free PSA, intact PSA (an unsplit, inactive form of PSA) and the human kallikrein 2 (hK2). It can be used in combination with findings from the digital rectal exam, age, and your history of previous prostate biopsies. However, the cost of this test has been estimated to be around USD $500.

Apart from blood tests based on kallikreins (PSA, Phi and 4Kscore), advances in genomic and proteomic techniques have found other potential genomic markers detectable in the first stream of urine. However, urine tests for prostate cancer are expensive and are not used routinely, particularly after the introduction of pre-biopsy mpMRI.

• SelectMDx test

The SelectMDx test measures the urine's levels of messenger RNA (mRNA), a form of genetic material, of the HOXC6 and DLX1 genes, after a physical examination by prostate massage. These are found in excessive amounts in aggressive prostate cancer, and measuring them can help predict the aggressiveness of prostate cancer (e.g. Gleason score with majority of grade 4 or higher).

• ExoDx Prostate Intelliscore

The ExoDx test is another urine-based test that measures messenger RNA levels of target genes, ERG, PCA3 and SPDEF, which are found in high levels in clinically significant prostate cancer.

The unique feature of this test is that it relies on studying exosomes, small protective sacs which break off from tumor cells and carry cellular proteins and genetic material. They are useful for predictive tests as they protect genetic material, making them a rich source of information for risk assessment.

Beyond that, the test scoring algorithm also does not require a physical examination (by prostate massage) to determine your risk.