Advancements in Testicular Cancer Biomarkers

Found in blood, other body fluids or tissues, a biomarker is a biological molecule that acts as a sign of normal or abnormal processes, or of a condition or a disease, according to the National Cancer Institute. Some biomarkers are general, and some are very specific to a certain type of cancer, and researchers are discovering more constantly, leading to very advanced detection and individually targeted treatments.

Fortunately, even though it is rarer than other cancers, testicular cancer has a few known biomarkers that can aid in early detection and treatment, and research is ongoing.

Testicular cancer usually affects men ages 15 to 34, but it is not as common as some forms of cancer. About 1 in 250 men will develop testicular cancer in their lifetime. Oncologists can often treat this type of cancer successfully, which means the risk of dying from testicular cancer is low.

Testicular germ cell tumors are very different when compared to other solid cancers. They are unique in the way they present, grow and respond to treatment. Because of this uniqueness, the hunt for new and effective biomarkers is essential in pursuing targeted therapy.

Clinicians are currently using biomarkers to treat testicular cancer, which is exciting, but the future has medical experts even more excited.

Justin Houman, M.D., a urologist and men's health specialist at Tower Urology in Los Angeles, explained that the main biomarkers for testicular cancer are:

• Alpha-fetoprotein (AFP)
• Lactate dehydrogenase (LDH)
• Human chorionic gonadotropin (hCG)

When high levels of these tumor markers—they can all be used for diagnosing, staging and guiding treatment—are found in the blood, it suggests a testicular tumor is present. However, the use of AFP, LDH and hCG in managing testicular cancer is limited, because nearly 50 percent of testicular cancers do not show any elevation in these three biomarkers.

The use of novel molecular biomarkers has significantly advanced treatment of many other solid cancers. For testicular cancer, however, reports on novel biomarkers have been few since the introduction of the above biomarkers more than three decades ago.

"These have been used for decades as biomarkers in diagnosing testicular cancer," Houman said. "Although much research has gone into finding newer biomarkers for testicular cancer, so far, none have a proven validated clinical role."

However, biomarkers are very beneficial in the treatment of advanced testicular cancer.

"Although the main blood biomarkers for testicular cancer haven't changed over the years, if you have metastatic testicular cancer, oncologists can do tests to look at the biomarkers within the genes of cancer itself," said Jennifer Linehan, M.D., a urologist and an associate professor of urologic oncology at the Saint John's Cancer Institute at Providence Saint John's Health Center in Santa Monica, California. "This helps your clinician decipher which treatments you are a candidate for."

"Usually, when an oncologist diagnoses testicular cancer, it needs to be treated right away," Linehan explained. "With testicular cancer, you very rarely put a patient on a surveillance protocol where they are not actively treated. Therefore, you don't need the layers of biomarkers that you find in other cancers, like prostate cancer."

However, she explained, tissue biomarkers—looking at the genetics and receptors of the tissue—have helped patients with advanced cases of the disease.

"This is because the medical oncologist can use them to pick out specific treatments that will work with their particular type of cancer," Linehan said. "Before using these biomarkers, there was a one-treatment-fits-all approach that was often unsuccessful. Biomarkers have changed the drugs that we can now offer patients with metastatic and complex cancers."

There is a need for new biomarkers in testicular cancer care. The current serum biomarkers—AFP, LDH and hCG—will continue to be part of routine care, but there is room for improvement.

Ribonucleic acid (RNA) is a molecule similar to DNA (deoxyribonucleic), but it is single-stranded rather than double-stranded. MicroRNAs are another type of tumor marker showing promising potential. They are small RNAs secreted by testicular tumor cells. You can measure them in body fluids, such as those collected during a liquid biopsy.

Liquid biopsies are at the forefront of cancer research and could play a valuable role in diagnosing testicular cancer. A liquid biopsy analyzes bits of tumor material—including microRNAs—found in bodily fluids, such as blood and urine.

Unlike many cases involving other solid cancers, if doctors find a mass in your testicle, the testicle and not just the mass is generally removed without a tissue biopsy.

"You would rarely do a tissue biopsy of a testicular mass, as there is a risk that it can cause cancer to spread," Linehan said.

Rather than just presumptively removing the lump/testicle without knowing whether it is cancerous, a liquid biopsy could help diagnose testicular cancer without the need for a tissue biopsy.

There is a highlighted need to diagnose testicular tumors noninvasively. However, there are still many unanswered questions regarding liquid biopsies in testicular cancer, and further research is needed.

"These novel biomarkers will help us to reduce morbidity associated with treatment," Houman said. "They can help us to accurately identify the difference between those who need to be treated and those who just need to be observed."