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How Liquid Biopsies Could Transform Insurance Medicine

Liquid Biopsy long

It sounds like the stuff of science fiction. 

Cancerous tumors shed whole cells or tiny bits of DNA and other genetic material into the bloodstream and other bodily fluids. This allows clinicians to potentially analyze blood samples to detect a tumor's unique mutations and offer a personalized treatment regimen, all without an invasive tissue biopsy. 


Science fiction is swiftly becoming reality according to Dr. Daniel Zimmerman, Senior Vice President and Chief Medical Director, Global Support Team for RGA. With a background in molecular biology and medical microbiology, Dr. Zimmerman is board-certified in internal medicine and pediatrics and has more than a decade of experience in insurance medicine. He makes the case in the interview below that liquid biopsies have the potential to transform clinical and insurance medicine by enhancing risk selection and potentially improving mortality and morbidity.

This post is the second in a two-part interview with Dr. Zimmerman based on his webinar “Epigenetics and Liquid Biopsies: Fact, Fiction or Both.” Read Part I and view the webinar here. 


First, define “liquid biopsy.”

Liquid biopsies are noninvasive tests to detect and classify cancers by identifying the small amounts of genetic material that tumors shed into the bloodstream or other bodily fluids. 

Start with a traditional biopsy. As underwriters or claims adjudicators know, the traditional diagnosis of cancer relies on a histopathological specimen. How is that obtained? First, a doctor has to physically perform a biopsy of a suspected tumor, either via needle or an open procedure.  The specimen is then sent to a laboratory. Technicians there make many thin slices of this biopsied material, which are placed on a glass slide, stained, and viewed under the microscope by a pathologist.

In contrast, a liquid biopsy involves no surgery or invasive procedures, usually only a blood draw. There are two basic types. One tests for circulating tumor cells that break away or get separated from the main tumor mass. The second type detects DNA, RNA, or other materials that enter the bloodstream when a tumor cell breaks open and spills these contents.

Why is there so much buzz around liquid biopsies right now?

Performing a traditional biopsy involves surgery or an invasive procedure and therefore can have complications. For example, a lung biopsy could result in a collapsed lung or bleeding.

Science is always looking for a better way to screen, diagnose, and manage disease, and there is essentially little to no risk associated with a liquid biopsy. Also, liquid biopsies can be performed when there's not enough tissue available or that tissue is hard to reach.

So liquid biopsies are safer.

There are other advantages, too. Traditional biopsies present a one-time opportunity because they are so invasive: Rarely do doctors go back in and re-biopsy a tumor. In contrast, a liquid biopsy can be performed multiple times. Why is this important? Liquid biopsies address the problem of inadequate sampling size error. There are times when a physician biopsies a mass or tumor and only later determines that there were insufficient tumor tissues for a diagnosis.

Tumors also change over time, and so liquid biopsies allow physicians to monitor that evolution. Currently, for example, a cancer patient undergoes surveillance after treatment to look for recurrence; this may take the form of scans or other tests. If you could detect the DNA or other genetic products earlier from a recurrence or changes in a cancer as part of regular liquid biopsy tests, physicians could change or initiate treatment faster.

Liquid biopsies also address the problem of intra-tumor heterogeneity and assessing metastatic lesions. Basically, a tumor is a mass of cells, but all those cells are not the same; different cells can have quite different genetic variations. A single tissue sample collected for a traditional biopsy could miss important mutations with very different prognostic implications just millimeters away. By contrast, a liquid biopsy should reflect all the variation present.  Similarly, metastatic lesions also have genetic differences and these can also be detected, theoretically, by liquid biopsies.   

No wonder so many people are enthralled by the promise of liquid biopsies. What is hype and what is reality?

It’s important to keep a sense of balance. To evaluate any of these new tests, large groups of individuals will need to be evaluated through clinical studies. That’s going to take some time.

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Having said that, we already have something similar to liquid biopsies in wide use. Underwriters  are very familiar with the PSA, CEA, and the AFP (alpha fetal protein) tests performed on blood samples. These are tests for biomarkers of tumors.  They don’t actually identify tumors directly, but they do detect certain biochemical changes that signal a tumor could be present. We know from experience that these tests are quite imperfect.

We must also recognize something called lead time bias. For example, say a screening test picks up breast cancer months or even years before the patient might actually feel a lump. This “lead time” allows doctors to identify and treat the cancer earlier, but this extra time may or may not confer an actual survival advantage. I don’t want to imply that earlier detection of cancer is not of value.  Often times it is very beneficial, but we need to be careful to make sure that we don’t identify tumors that may have no impact on life expectancy and “over treat” the patient. 

Finally, clinicians must differentiate between “driver” versus “passenger” genetic variations   detected by liquid biopsies.  A driver mutation is the root cause or explains why a tumor is growing. A passenger genetic variation may have nothing to do with tumor growth. This adds an extra layer of complexity when it comes to interpreting liquid biopsies.

This all seems very complex and qualified. How should insurers evaluate these tests?
Like any test, insurers should rely on three criteria to assess the use of liquid biopsies in insurance medicine: analytical validity, clinical validity, and clinical utility. When we look at any test result, we need to determine if the test is reproducible and reliable. That’s analytical validity: If I send a sample to three different laboratories, will I get the same result back?  Then, there’s clinical validity: Does the result have value in determining whether someone will or will not develop an impairment or does it provide prognostic value

Then, there is clinical utility: Is the test result actionable? Can test results be applied to improve patient outcomes, inform behavior or influence treatment decisions?

Last, insurers need to consider local regulation regarding use of genomic information in insurance.  Most, but not all, liquid biopsies would likely be considered genetic tests and thus may be subject to regulation. 

Put liquid biopsies in an insurance context. How will these potentially impact our industry?

Historically, medical advances which have led to improvements in morbidity and mortality have generally benefited the insurance industry as well as the general population. Having said that, certain advances can be very challenging. Anti-selection is always a risk. Also existing critical illness product definitions can pose problems.

For example, when the clinical definition of myocardial infarction changed, interpreting certain critical illness definitions of myocardial infarction became quite difficult and changed what we had calculated as the expected incidence rates. Liquid biopsies might likewise change the basis of cancer diagnosis and incidence rates, and impact product pricing. Consider the critical illness products on the market today. Any pathologist testing a tumor is looking for the same factors that insurers have incorporated into a standard cancer definition of most critical illness policies: histological confirmation characterized by the uncontrolled growth of malignant cells with invasion and destruction of normal tissue. This traditional diagnosis of cancer is based on a traditional biopsy, not a liquid biopsy. Early, multi-pay, staged, and even high-severity types of products could be affected by definitional changes.

Time will tell if early detection and more focused treatment of tumors might lead to improved outcomes and less time off work, reducing claims for disability or income protection products. Then there is health cover: We might see lower initial costs for liquid biopsies compared to traditional biopsies and liquid biopsies could lead to more focused or more personalized care that actually could increase costs in the short term due to expensive new therapies.  But in the long term we may see improved mortality and possibly eventual reduction in treatment costs depending on the marketplace.  

So what is the bottom line on liquid biopsies?

Bottom line: Liquid biopsies will almost certainly impact the insurance industry in the years to come, but to what extent has yet to be determined. Vigilance in keeping up with the latest research and discoveries will be essential in successfully navigating this evolving issue.



This post is the second in a two-part interview with Dr. Zimmerman based on his webinar “Epigenetics and Liquid Biopsies: Fact, Fiction or Both.” Read Part I and view the webinar hereRGA's medical team has also published an in-depth white paper on liquid biopsies, available for viewing and download here

RGA’s team of doctors, located in offices around the world, is dedicated to sharing the latest medical information and expertise in order to meet our clients’ needs and move the industry forward.

The Author

  • Dr. Daniel D. Zimmerman
    Senior Vice President and
    Chief Medical Director
    Global Support Team
    RGA
    Send email >

Summary

Cancerous tumors shed whole cells or tiny bits of DNA and other genetic material into the bloodstream and other bodily fluids. This allows clinicians to potentially analyze blood samples to detect a tumor's unique mutations and offer a personalized treatment regimen, all without an invasive tissue biopsy. 

This post is the second in a two-part interview with Dr. Zimmerman based on his webinar “Epigenetics and Liquid Biopsies: Fact, Fiction or Both.” Read Part I and view the webinar here. RGA's medical team has also published an in-depth white paper on liquid biopsies, available for viewing and download here



  • antiselection
  • anti-selection
  • Biomarker
  • biopsy
  • blood test
  • cancer
  • DNA
  • epigenetic
  • genetic
  • genome
  • Global Support Team
  • innovation
  • insurance medicine
  • liquid biopsy
  • medical innovation
  • medical underwriting
  • Quantified Self
  • ReFlection
  • ReFlections
  • RNA
  • webinar
  • Zimmerman