Can Blood Analysis Be Used to Detect Cancer?
- Liquid biopsies detect cancer signatures within the bloodstream. This can include tumor DNA, proteins, or intact tumor cells.
- These biopsies can detect early as well as late-stage cancers. However, they may not work for all cancer types.
- Standard biopsies (which sample a piece of tissue from the body) are still the mainstay of a cancer diagnosis. Liquid biopsies are a complementary technique.
- Future scientific studies are needed to show the benefit of liquid biopsies over more standard biopsies and procedures.
- Greater physician education is required to ensure the appropriate and judicious use of liquid biopsies.
Present methods of cancer detection rely on invasive and often uncomfortable tests that ultimately extract a portion of body tissue for analysis in a process called a biopsy. This tissue is analyzed in myriad ways before cancer is diagnosed or ruled out. Yet even this process is not foolproof.
Read MoreThe promise of liquid biopsies
Expanding blood testing to detect a great number of diseases, including cancer, is a hot topic in the medical world. If patients can conveniently have their blood tested for cancer at a local facility such as a Quest Diagnostics or LabCorp, the improvement in cancer care could be revolutionary. More people could get screened, more cancers could be detected, and more lives could be saved. Hence, academic centers and medical industry giants are devoting tremendous resources to accomplish this.“So I think that that’s going to require large, very large clinical trials to demonstrate the value of these sort of multi-cancer detection tests,” Dr. Craig Bunnell, the chief medical officer at the Dana-Farber Cancer Institute and associate professor of medicine at the Harvard Medical School, tells SurvivorNet.
“I think there’s tremendous promise in being able to do a blood test and pick up cancers very early or even in a pre-cancerous state in which we can actually prevent the development of those cancers,” said Dr. Bunnell.
But he warns the ability to actually find people with pre-cancerous conditions or who would qualify for these trials is a difficult task.
“There’s tremendous promise in that, at the same time, we have to know that administering those tests; what’s the sensitivity of those tests? What’s the specificity of those tests? A test isn’t good if it just picks it up, but you can’t intervene early enough. You have to make sure that those tests are really bringing value, adding improvements in survival, in quality of life, et cetera. And that’s going to require very large clinical trials to do that.”
Related: FDA Approves Blood Test Which May Let Some Cancer Patients Avoid Additional Biopsies
Current cancer screening methods can only detect a limited number of cancers, such as colon and breast cancers. Pancreatic, small bowel, and stomach cancers are among many cancers that are not covered by the current methods. A liquid biopsy has the potential to screen for these cancers too and could pick them up at earlier stages. This would give patients with these cancers a much better fighting chance for a cure.
"Ultimately, there is a chance that these biopsies can become cancer screening tests like the PSA, which is used to detect prostate cancer. However, we require a fair number of clinical studies before we get to that point," proclaims Dr. Jennifer Johnson, a medical oncologist and an associate professor at the Sidney Kimmel Cancer Center at Thomas Jefferson University. The research is currently being unveiled at distinguished cancer conferences around the world agrees.
The blood holds important clues
A liquid biopsy detects tumor cells or pieces thereof, including tumor DNA, in a blood sample. Traditionally, to be detected, cancer must be large enough to be seen by medical imaging and diagnostic procedures. A liquid biopsy skips this requirement. It uses microscopic technology to pick up cancers that are invisible to the eyes of humans or machines. Therefore, it can pick up cancers at early stages, before they get bigger and more resistant to treatments.
"Another obvious benefit of a liquid biopsy is when tissue used for traditional biopsy just isn't available. It could happen in tumors that do not have obvious lesions that we can sample or tumors that are very inaccessible," says Dr. Johnson. She relates a personal anecdote where she ordered a liquid biopsy for one of her patients after two attempts at a traditional tissue biopsy.
"Rather than subject him to a third attempt, which I did not think was going to be successful, I obtained a blood (liquid) biopsy and started them on the standard of care treatment,” she said.
Liquid biopsies could also paint a more complete picture of the kind of cancer afflicting patients.
Dr. Johnson emphasizes, "If there are multiple sites of disease, you can get a liquid biopsy that would more holistically represent the molecular profile of their cancer as opposed to getting a biopsy of just one spot of disease. Biopsying a single spot may not be representative of the tumors present elsewhere in the body." A more comprehensive picture of patients' cancers through liquid biopsies can help clinicians choose the best drugs for them, which can in turn lead to improved clinical outcomes.
Moreover, for people already living with cancer, tumor markers within the blood can indicate how well they are responding to their treatment. If a tumor continues to have a strong presence within the blood despite treatment, it clues the physicians in to try another, possibly more efficacious treatment. Conversely, if the tumor presence within the blood starts to decline after a certain treatment, it speaks to the effectiveness of that treatment.
For those who have won their battles against cancer, liquid biopsies can be used to monitor for signs of cancer returning. Should the cancer return, early detection can improve the quality of a patient's life in addition to extending it.
What evidence is there on these biopsies?
A recent study published in the highly acclaimed scientific journal Nature showed that assessing tumor indicators within the blood through high-definition liquid biopsies can very accurately detect people with early, late, or metastatic breast cancers and those without cancers.
The test used in the study detected oncosomes. These are small packets of signals derived from the cancer cells and released into the bloodstream. They contain small cargos that are unique to the tumor cells that secrete them. Characterizing these oncosomes, therefore, can reveal the specific cancer afflicting the patient. Most notably, even early-stage breast cancers express these oncosomes at detectable levels.
Beyond breast cancers, similar tests have been used to detect other types of cancer as well. A hot-off-the-press study measured tumor DNA within the blood of over 6,000 patients aged 50 or older without any history of cancer. Cancer DNA was detected in 1.4% of the patients. One year after testing, 38% of these patients had a confirmed diagnosis of cancer. In other words, the test had a positive predictive value (PPV) of nearly 40%. PPV describes the probability that someone who tests positive for a disease actually has that disease.
Are these biopsies available to the public?
Liquid biopsies, such as FoundationOne Liquid CDx and Guardant360 CDx, have been available on the market for some time. However, their use in day-to-day clinical medicine is limited for now.
What are the benefits for cancer patients?
For any test to have real-world utility, it must be connected to an improved patient outcome. This has yet to happen for liquid biopsies.
For these biopsies to improve patient care, they need to be incorporated into clinical trials that investigate the meaningful relationships between the biopsy results and measurable patient outcomes, such as quality of life, overall survival, and progression-free survival.
OS, the ultimate measure of a treatment's efficacy, is defined as the length of time patients are alive after their initial diagnosis of cancer. PFS represents the time a patient is alive without a worsening of their disease.
The data from the aforementioned studies and their likes are, however, very encouraging. Thus, it is only a matter of time before a clinical trial that incorporates liquid biopsies into its design will demonstrate a meaningful improvement in the lives of cancer patients. Once that happens, clinicians will start to incorporate these tests into their daily clinical decision-making regularly.
Implementing liquid biopsies in clinical trials
What are the down sides?
Experts express some concerns about the use of liquid biopsies. For one, they are concerned about over-treatment. Over-treatment is when treatment that would have no real impact on a patient’s well-being or life expectancy is used.
In the world of cancer, there are certain kinds of cancers that are extremely slow growing. A patient with such cancer is much more likely to pass away from another condition, such as a heart attack or complications from diabetes, than they are to ever suffer at the hands of their cancer. If this patient receives cancer treatment, they may suffer side effects that could negatively impact the quality of their life for little or no benefit.
"That is the story of PSA, (a molecule that is secreted by the normal prostate gland as well as prostate cancer cells). We run the risk of over-treatment should such biopsies be used like the PSA initially was. However, we have also learned lessons from our over-reliance on PSA to justify treatment," notes Dr. Johnson. Sometimes PSA tests detect prostate cancer, but it does not need to be actively treated.
The cancer cells tend to make higher levels of PSA, which can be detected through blood testing. During the initial fervor for using PSA to screen for prostate cancer, there was an uptick in the number of patients receiving treatment for very slow-growing prostate cancers. Such cancers would have had little to no effect on the patients' health or longevity. All cancer treatments are associated with toxicity, and no one should receive them unless there are clear benefits. For this reason, PSA levels are now sometimes used to wait and watch a cancer instead of starting immediate treatment.
This story about the judicious use of PSA may help guide the appropriate use of liquid biopsies. In cases of very early-stage cancers identified by these biopsies, physicians may use them to keep an eye on a patient's cancer unless it meaningfully presents a threat to the patient's health.
This also underscores an immense need for healthcare provider education regarding the benefits, risks, and scope of these biopsies. "I worry that unless there is proper physician education, the power of liquid biopsies may be misinterpreted, especially when it comes to their improper use as replacements for and not as supplements to standard biopsies," expresses Dr. Johnson. Any benefit of standalone liquid biopsies has not been demonstrated in clinical trials. Until such evidence comes to the fore, these biopsies should be used as complementary techniques and not a replacement for standard-of-care testing.
Looking To The Future
Liquid biopsies hold a lot of promise, but their full potential is unknown. When considering the role these biopsies may play in your care or the care of a loved one, there are a few things that you should keep in mind:
- Liquid biopsies detect cancer signatures within the bloodstream. This can include tumor DNA, proteins, or intact tumor cells.
- These biopsies can detect early as well as late-stage cancers. However, this may not be true for all cancers. For example, they are good at detecting early-stage breast cancer but not kidney cancer. This may soon change with advances in technology.
- Standard biopsies are still the mainstay of a cancer diagnosis. Liquid biopsies are used as a complementary technique and not in lieu of standard biopsies.
- These biopsies have not shown any benefit over more standard biopsies and procedures when it comes to clinical outcomes, such as quality of life, overall survival, or progression-free survival. Future scientific studies must demonstrate such benefits for these biopsies to become a justified part of cancer care.
- Physicians in the community may not be fully familiar with this technique’s legitimate scope and limitations. Greater physician education is required to ensure the appropriate and judicious use of liquid biopsies.
In the words of Dr. Bunnell, "from a clinical and an ethical standpoint, there’s a ways to go on the liquid prophylactic testing world."
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