Cancer is the second-leading cause of death in developed countries. Prostate cancer is the second-leading cause of cancer death for American men. However, it's important to note that most men diagnosed with prostate cancer do not die from it. Early detection is the key to successful treatment.
Most people probably think of drugs, radiation therapy or surgery as forms of treatment. Medicine is moving beyond just those options, however. The research behind biomarkers and liquid biopsies for prostate cancer is quickly gaining ground.
"We are making tremendous progress as we start to understand the biology of the disease and find biomarkers that help clinicians to make better decisions," said Howard I. Scher, M.D., head of the Biomarker Development Program at Memorial Sloan Kettering Cancer Center in New York City. Scher is a board-certified medical oncologist with special expertise in treating men with advanced prostate cancer.
Drugs are important to treating cancer, but doing it successfully often requires more than medication. How do clinicians determine which treatments to use? Which test will give you and your treating physician the best chance for a better outcome? Once on a treatment path, how do you determine if it's working?
This is where biomarkers, biopsies and liquid biopsies come in.
Before delving into a discussion of liquid biopsies and prostate cancer, it's necessary to explain some terminology, starting with biomarkers.
A biomarker is a "biological molecule found in blood, other body fluids or tissues that is a sign of a normal or abnormal process, or a condition or disease," according to the National Cancer Institute. Biomarkers in oncology are usually markers that show cancer in the body or point to specific cancer features that might predict response to a treatment, or a prognosis.
Simply put, clinicians can use biomarkers to help diagnose and treat cancer.
To look at biomarkers, clinicians first must perform a biopsy. A traditional tissue biopsy is a procedure that removes a piece of tissue or a sample of cells from your body. Your healthcare provider can do this in several ways depending on the type of cancer suspected.
For example, the procedure might entail a needle being inserted into a breast lump to remove a sample of cells. In another case, an area of skin might be removed for a skin biopsy. In some cases, more extensive surgery may be needed to remove an area of tissue to biopsy.
However, a step forward in managing cancer in recent years has been the development of liquid biopsies. These are tests that identify biomarkers in blood or urine. Tissue biopsies have some limitations, and liquid biopsies have become a particular focus in cancer research, especially for prostate cancer.
The limitations of tissue biopsies
A 2022 review article published in the British Journal of Cancer discussed the limitations of using tissue biopsies of primary tumors or metastatic lesions when profiling prostate cancer and guiding a treatment plan.
Tissue biopsies remain the gold standard for cancer diagnosis, but they are only possible when a mass is detectable. It can also be difficult to get tissue from poorly accessible metastases, the parts of the body to which the cancer has spread. They can also be very invasive for patients.
"One of the other problems with prostate cancer and precision medicine is its pattern of spread is not like nodules or typical lymph node involvement," Scher said. "You may see lymph nodes in the pelvis, but then you may find some sites in bone. Getting enough tumor material to do any kind of profiling is tough."
That is where a liquid biopsy becomes useful. A blood test is a lot easier than trying to get a tissue sample from bone.
Prostate cancer that has spread to multiple locations can also be biologically different in each area, Scher explained. So you can take a tissue biopsy from lesion X, but lesion Y may differ.
"If you do a liquid biopsy via a blood test, for example, you increase the chance that you're going to get a sampling of more than one tumor," he said.
This is why there has been an increasing interest in blood-based biomarkers in recent research.
But how are liquid biopsies currently used in prostate cancer management?
Liquid biopsies for prostate cancer
A physical exam with a digital rectal exam, a PSA blood test, a prostate biopsy and a prostate MRI are the current keystones to the diagnosis of prostate cancer and its proper staging.
But clinicians now also use liquid biopsies in prostate cancer screening, said S. Adam Ramin, M.D., a urologic surgeon and the medical director of Urology Cancer Specialists in Los Angeles.
Ramin explained that liquid biopsies are used as a screening test to detect RNA strands in urine that are known to be functioning when prostate cancer is present. Ribonucleic acid (RNA) is a nucleic acid present in all living cells and has structural similarities to DNA.
"In prostate cancer, certain genes become active," Ramin said. "Those genes are transcribed into RNA strands. The RNA strands then code for certain proteins that are active in prostate cancer. [But] liquid biopsy tests do not definitively diagnose prostate cancer. A positive test triggers the need to do an actual tissue biopsy of the prostate."
The prostate-specific antigen (PSA) test is not always an accurate screening test for prostate cancer, Ramin explained. Not all patients with elevated PSA levels need to undergo an invasive prostate biopsy to determine the presence of prostate cancer.
"In patients with elevated or abnormal PSA tests, we can do additional testing to determine if an actual tissue biopsy is required," Ramin said. "One of the additional tests is a liquid biopsy. Another additional test is an MRI of the prostate."
Ramin advised that liquid biopsy tests are generally associated with detecting RNAs related to more aggressive types of prostate cancer.
"The less aggressive prostate cancers generally carry a very small risk spread," he said.
The future of liquid biopsies for prostate cancer
"At this time, liquid biopsy tests are not used for diagnosis and, therefore, are not used for determining the best modality of treatment," Ramin said.
But emerging studies show liquid biopsies could be used to guide the diagnosis and treatment of prostate cancer.
Circulating tumor cells (CTCs) present as valuable biomarkers. They are rare, though, and represent approximately one cell surrounded by a billion red blood cells in the bloodstream. A clinical study led by Scher showed that detecting CTCs through a liquid biopsy can help doctors determine which drugs are likely to work better in patients with disease that is resistant to initial treatments.
"This is what we call precision medicine," Scher said. "You can use liquid biopsies to help choose the drugs most likely to benefit the patient and avoid those that won't. And that's a big deal."
Liquid biopsies can provide a comprehensive, real-time assessment of tumor characteristics and offer insights into early diagnosis, prognosis and treatment efficacy in prostate cancer, according to a 2021 review published in the journal the Aging Male.
Still very much in the research stages, liquid biopsies in the near future may well be able to diagnose prostate cancer, assess if it requires treatment and guide the best treatment options for the individual.
"The opportunities are, I don't want to say limitless, but they are limitless," Scher said. "It's really a matter of designing the right scientific trials to ensure the tests are accurate."