What to Ask About Molecular Testing for Lung Cancer
- Molecular testing in lung cancer is a complex, and rapidly evolving topic.
- A variety of molecular tests may be used in non-small cell lung cancer, including PD-L1, testing for specific DNA mutations, and next generation sequencing
- These tests are performed to help doctors determine which medications will be the most effective at targeting and killing the lung cancer.
- The costs of these tests can vary based on several factors. Dr. Chul Kim, a medical oncologist at MedStar Health in Washington, D.C., explained that the tests will frequently be covered by insurance if they are ordered based on “standard guidelines.”
It can be difficult to understand all of your options and potential therapies, which is why it is important to be in constant communication with your healthcare team regarding what is the best choice for you and your cancer.Read More
What is molecular testing?Molecular testing is a broad term that uses detection of individual molecules or pieces of cancer cells to better characterize a cancer, its behavior, and potential targeted (and more effective) treatment options. Molecular testing can also be used to test pieces of a cell, such as DNA, to identify hereditary cancers (Germline mutations) or mutations in the cancer DNA (Somatic Mutations).
What type of molecular testing is available for lung cancer?
There are a variety of molecular tests that are available for lung cancer. Common tests include PD-L1 testing, specific genetic testing, and next generation sequencing.
What is PD-L1 testing?
PD-L1 testing takes tumor cells gathered from a biopsy and identifies the level of expression of a protein called PD-L1, which is used to turn down the immune response. The higher the expression of PD-L1 on tumor cells, the more it turns down the immune response by your own body.
This helps doctors determine how effective treating the cancer with immunotherapy would be. The PD-L1 score is typically reported as a percentage, with <1% being no PD-L1 expression, and a higher percentages showing more expression.
What is specific genetic testing?
There are certain mutations in the DNA that are more common — such as EGFR, KRAS, and ALK — that can be tested for by using a piece of tissue from a biopsy. These are commonly done in the work up for lung cancer of early and locally advanced lung cancer.
What is next generation sequencing?
Next generation sequencing (NGS), typically done via a tissue biopsy, analyzes multiple portions of the tumor DNA to identify several potential markers or DNA mutations that can be targeted for treatment.
Next generation sequencing can be done via tissue biopsy which tests a piece of the tumor, but if there is a need for repeat biopsy and an additional biopsy procedure is not feasible or unsafe, NGS can also be performed with a liquid biopsy.
How is molecular testing done?
A liquid biopsy, which collects a sample of your blood and analyzes pieces of cancer cells that are in the blood stream called circulating tumor DNA or ctDNA, may be used. This sample can then be tested using NGS to determine targetable mutations.
Why use a liquid biopsy?
Tissue biopsy is the gold standard for biopsy and testing for NGS. However, if tissue biopsy is unfeasible and repeated NGS is needed to test for ongoing changes in the cancer DNA, liquid biopsy can be a less invasive and repeatable alternative to tissue biopsy.
When is molecular testing used in lung cancer?
Different molecular tests will be employed depending on the stage and type of lung cancer, as well as response to prior therapies.
When discussing lung cancer there are two main types, small cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is where a majority of molecular testing is performed. In early and locally advanced NSCLC, a workup is performed with history and physical exam, lab tests, imaging, and biopsy.
Additional molecular testing performed on the biopsy typically includes PD-L1 testing and genetic testing for common mutations known to cause lung cancer such as EGFR, KRAS, and ALK.
In metastatic (advanced) disease, next generation sequencing is also performed — and it looks a multitude of potential DNA mutations that could be targeted by systemic therapy. Sometimes multiple molecular tests can be run in patients with metastatic disease to test for development of new mutations when the disease has progressed or stopped responding to the current systemic therapy. In this case, liquid biopsy can be used to reduce morbidity of repeat tissue biopsy.
How can molecular testing change treatment?
Dr. Chul Kim, a medical oncologist specializing in lung cancer and thoracic tumors at MedStar Health in Washington, D.C., explained that the terminology associated with molecular testing can be confusing for a lot of patients, but the results of these tests are very important.
“There are various terms that you will hear from the doctors — biomarkers, mutations, genomic alterations, genomic changes — and these sometimes can be used interchangeably and can be confusing because you hear different terms. But these mean most of the time the same thing,” Dr. Kim explained. “So the reason why we talk about molecular testing is to understand the cancer’s biology and behavior and to find right treatment.”
In early stage and locally advanced NSCLC, molecular testing can provide valuable information such as how effective immunotherapy may be, as well as potential targeted therapy options than can be used in conjunction with chemotherapy, radiation, or surgery.
The exact order and combination of therapies depends on several factors including stage, tumor location, overall health, lung cancer type, and treatment goals to name a few.
In metastatic disease, systemic therapy is the mainstay of treatment (this means therapy that treats the whole body rather than targets one specific area). Next generation sequencing is performed to evaluate a multitude of potential targetable DNA mutations. Depending on the specific DNA mutation, there can be several targeted therapies which can be used and change throughout the course of your disease based on response to therapy and disease progression.
How much do these tests costs?
The costs of the molecular testing can vary based on the complexity of the test and the type of the test, typically with next generation sequencing costing more than straightforward molecular testing — which only looks at a few molecular markers.
Next generation sequencing is a relatively new technology, but the price has continued to decrease for several reasons over the past decade, including continued technological advancements, market competition, economic scalability.
Dr. Kim explained, “It is important to understand the type and stage of the cancer in order to know whether that will be covered. I can reassure you that most insurance plans cover the tests if the test was ordered based on the standard guidelines.”
If you have further questions regarding testing and the financial implications, you should discuss further with your healthcare team.
What are specific genes examined in molecular testing?
DNA mutations that are commonly examined with molecular testing include:
- METex14 skipping
- ERBB2 (HER2)
The future of molecular testing
As research continues with molecular testing in lung cancer, there continues to be more targetable DNA mutations identified, with further personalization of therapy.
Additionally, targeted therapy continues to become more active and better tolerated.
“We are realizing more and more the importance of germline testing based on certain studies. So we may see a greater value of germline testing in lung cancer in the future”, Dr. Kim noted. This means testing for inherited DNA mutations for lung cancer is something we might see in the future.
What else should I ask my doctor?
How much are these tests going to cost me?
Costs can vary based on your insurance provider and test obtained. This can be discussed further with your healthcare team.
What should I expect to go through with each test?
Biopsy of the lung or metastatic site is often required for molecular testing and is a procedure which can cause some pain and discomfort following. If a liquid biopsy can be performed, it involves collecting blood, like a routine blood work.
Are clinical trials available?
Clinical trial availability will vary based on your specific disease and the site where you are receiving treatment.
Check out SurvivorNet’s simple Clinical Trial Finder.