How Biomarkers Can Inform Prostate Cancer Decisions

By Dr. Dan Sperling

What are biomarkers?

Scientific research continues to find new keys that unlock the mysteries of prostate cancer (PCa).

One of those mysteries is understanding the specific nature of each patient’s disease. We now know that not all PCa cells are identical because each patient’s genetic makeup is unique. Thankfully, there are ways to test for genetic variants or mutations that indicate the danger level of a man’s PCa. We call these variants biomarkers because they are measurable biological substances that can be found in blood, urine or tissue and act as a kind of PCa cell line signature, or marker.

Identifying a patient’s biomarkers before prostate biopsy or treatment can help determine the best decision for him. If we know how mild or aggressive his disease is, we can strategize the best course of action. It’s like tailoring a man’s suit to his exact measurements. The better the fit, the more successful he looks. Similarly, the better a treatment fits a patient’s cancer, the more successful the treatment is likely to be.

Another way to think of biomarkers is like a color vs. black-and-white photo of a person. Color brings out extra information. In black and white, you usually can’t tell hair or eye color, whether their skin tone has a warm or cool shade to it, and how well the palette of their clothes enhances their natural coloring. Analyzing a PCa patient’s biomarkers brings out details that enhance the probability of successful treatment.

Types of liquid biomarkers

There are several different types of PCa biomarker tests that add useful information. Blood and urine samples can be analyzed before a prostate biopsy to help determine if whether a needle biopsy is necessary. In addition, once a biopsy is done the tissue samples that contain prostate cancer can provide actual PCa cells for further analysis.

Here are some liquid biomarker tests (blood, urine) that are currently available:

• Prostate Health Index (PHI) is a blood test done before a biopsy to help decide if a biopsy is right for the patient. Most men know about the PSA (prostate specific antigen) screening test, but the PHI test uses a more complex analysis of PSA than the basic test.
• 4K Score test is also a blood test prior to a biopsy. The results of the blood test are combined with additional factors (age, digital rectal exam, prior biopsy if done) to generate a personal risk score. The greater the risk, the higher the probability that the cancer is aggressive and requires appropriately aggressive treatment.
• PCA3 Score is a urine test that measures a specific type of protein (PCA3) that is present when abnormal prostate cells, usually cancer, are growing in the prostate. It is generally recommended only after a previous negative biopsy has already been done. A high concentration of PCA3 strongly suggests cancer is present, though it may also indicate a precancerous condition called high grade PIN).
• Circulating tumor cells (CTCs) are PCa cells that are shed into the bloodstream and can be counted or subject to further genomic analysis from a blood sample. A high number of CTCs is associated with aggressive PCa tumors, and possibly with tumor spread (metastasis). However, this tool is not yet in common clinical use.

Types of tissue biomarkers

Tissue samples obtained by biopsy needles allow genomic analysis of the prostate cancer cells they contain. Here are tests that are currently available:

• Decipher Genomic Classifier analyzes biopsy tissue for 22 known gene variants. It is considered the most validated gene test for doctors and patients to assist with treatment decisions.
• Prolaris tests for the presence of 31 cell cycle progression genes that cause PCa cells to proliferate. Combined with a patient’s Gleason score and PSA, Prolaris calculates the probability of metastasis and PCa-specific mortality 10 years after treatment.
• Confirm MDx analyzes biopsy tissue for the biochemical effect that cancer development has on neighboring normal cells. Evidence of a “field effect” on healthy cells may point to the existence of cancer even if a current or previous biopsy was negative for cancer but PSA is persistently high. It has a high negative value (if it says there’s no cancer, there’s probably no cancer) but doesn’t distinguish aggressive from indolent PCa.
• Oncotype DX tests biopsy samples for 17 genes. The specific cancer genes have a distinct fingerprint linked with the onset, growth and proliferation of PCa tumors. Results are presented as a Genomic Prostate Score (GPS) with higher scores indicating more dangerous cancer.

Biomarkers plus imaging

When the use of biomarkers is integrated with multiparametric MRI (mpMRI) of the prostate, it revolutionizes the detection and diagnosis of each patient’s individual disease portrait. Given the growing availability of powerful 3T (3 Tesla) magnets, and the number of experienced radiological readers, imaging is able to rule biopsy in or out; mpMRI has demonstrated the ability to detect the size, shape and location of significant cancer. If a biopsy proves necessary, mpMRI can guide a precise targeted biopsy to capture tissue for genomic analysis. Biomarkers add information at the cellular level to characterize the nature and behavior of the PCa cells. Thus, the combination of mpMRI plus biomarkers is today’s ideal diagnostic pathway, offering the richest aggregate of clinical information for decision-making.

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