Advancements in Prostate Cancer Biomarkers

Second only to skin cancer, prostate cancer is the cancer American men are most likely to contract and is also the second-leading cause of cancer death following lung cancer. Affecting 1 in 8 men, it is a prevalent disease. However, most men diagnosed with prostate cancer do not die from the condition.

Researchers are continuously progressing diagnostic and treatment methods for prostate cancer. A lot of this research is focused on biomarkers.

"Essentially, a biomarker is a molecule found in the body, whether in blood, tissues or body fluid, that is indicative of a normal or abnormal biological process," said Justin Houman, M.D., a urologist and men's health specialist at Tower Urology in Los Angeles.

Oncologists use biomarkers to diagnose, predict prognosis and guide treatment of cancers. However, biomarker tests vary significantly from cancer to cancer. So let's take a quick look at the use of biomarkers in prostate cancer detection and treatment.

"In prostate cancer, biomarkers are initially used for screening," said Jennifer Linehan, M.D., a urologist and associate professor of urologic oncology at the Saint John's Cancer Institute at Providence Saint John's Health Center in Santa Monica, California. "[They're used] to decipher if a person is either at risk of prostate cancer or has prostate cancer and, if so, to establish if further tests, like a biopsy, are needed."

In addition to screening, doctors know of many levels of biomarkers that can be used in prostate cancer care. Linehan explained that biomarkers in prostate cancer could be used for the following:

• Pre-diagnosis: Initial screening and determining if further tests are needed (diagnostic biomarkers)
• Post-diagnosis: Deciphering the grade of prostate cancer and how aggressive it is (prognostic biomarkers)
• Post-treatment: To establish the probability of prostate cancer returning (prognostic biomarkers)
• Post-treatment: To determine the best further treatment options for advanced prostate cancer that has spread (stratification biomarkers)

"There are biomarkers that can be used at every stage of prostate cancer, but that is not the case for most cancers," Linehan said. "For example, there are only simple biomarker blood tests for pancreatic cancer that can be used for screening or to see if treatment is working."

Biomarkers for prostate cancer can be measured in blood, urine, prostatic fluid or prostate tissue.

"As with every disease, we are learning more and more about prostate cancer," Houman said. "PSA [prostate-specific antigen] has been a longstanding screening test for prostate cancer. However, new biomarker tests are providing more insight into prostate cancer screening, diagnosis and treatment."

Houman discussed other types of biomarkers and the newer tests that look for them. Building on the success of the PSA test, the Prostate Health Index (PHI) is a simple, inexpensive blood test that uses three PSA measurements to improve prostate cancer screening and reduce the number of invasive biopsies required.

Another area of interest to biomarker researchers is what are called exosomes, or extracellular vesicles. One company has a urine-based exosome test that helps medical folks assess high-grade prostate cancer risk.

Another urine-based test is used for risk assessment of high-grade prostate cancer. It measures the mitochondrial RNA expression levels of two biomarkers, HOXC6 and DLX1, and combines those results with clinical risk factors, such as age, race and family history, to identify men who should undergo magnetic resonance imaging (MRI) and/or a prostate biopsy.

Finally, PCA3 is a protein biomarker made by normal prostate cells. People with prostate cancer make more of this protein than usual, and it can be found in urine. While the PCA3 test, a genetic test to detect PCA3, can't diagnose cancer on its own, it can help doctors decide whether you need a biopsy.

These are just a few of the biomarker tests available in prostate cancer.

"No single biomarker alone has perfect performance characteristics," Houman said. "Various biomarker tests together should be part of the multivariable approach to appropriate screening, diagnosis and treatment of prostate cancer."

"With prostate cancer, treatment is not always necessary straight away," Linehan said. "That is why there are so many levels of biomarkers—because there are so many different levels of treatment for prostate cancer."

Linehan acknowledged that biomarkers in prostate cancer can be confusing and seem to many patients like a lot of extra testing. Given that biomarkers can help clarify what is going on, those extra tests should be reassuring.

"Where biomarkers become incredibly important is in the treatment of metastatic cancer," she said.

Linehan explained that in cases of advanced prostate cancer, where a patient has stopped responding to treatment, biomarkers could identify what treatment option would work best for that individual.

"It has changed what drugs we can offer to these patients, which has really helped progress treatment options," she said.

"The future question is whether we will be able to diagnose cancer purely from a liquid biopsy from the blood or urine," Linehan said, adding that liquid biopsies are quickly gaining ground as a method.

The aim is for liquid biopsies to be able to:

• Identify the presence of cancer
• Pinpoint the location of cancer in the body
• Assess if cancer requires treatment
• Guide the best treatment options for that cancer and individual

"This is likely coming in time, and it will help diagnose cancer sooner, before there are visible signs," Linehan said.

However, she added that this development raises questions regarding what to do if microscopic cancer cells are found in the blood or urine, but all other tests are clear. What is the best course of action? How early is too early to treat? At worst, clinicians could use this information to pinpoint patients who need screening more often.

"The most significant benefit of biomarker research is understanding genetic mutations," Linehan continued. "The more we know about genetic mutations, the more we can understand targeted treatment and prognosis."

Houman said that as biotechnology continues to advance, next-generation biomarkers will not only help identify who has prostate cancer, but also who needs treatment.

"Based on the next-generation biomarkers, we will be able to reduce any morbidity associated with treatment by identifying who actually needs treatment versus being observed," he said.