Value of Germline Genetic Testing for All Patients With Gastrointestinal Cancers Irrespective of Tumor Origin

At Great Debates and Updates in Gastrointestinal Malignancies in New York, New York, Michael Hall, MD, MS, Fox Chase Cancer Center, Philadelphia, Pennsylvania, discussed limitations to performing germline genetic testing on all patients with gastrointestinal cancers. 

Transcript: 

My name is Dr Michael Hall, I'm a gastrointestinal oncologist from Philadelphia, Pennsylvania.I work at Fox Chase Cancer Center where I am the chairman of the department of clinical genetics, I practice within the GI oncology group, and I'm the co-lead of our cancer center program known as cancer prevention and control. I'm really thrilled to be here at Great Debates 2024 for GI cancers in New York City. I was part of a debate today with Dr Zsofia Stadler from Memorial Sloan Kettering and we were debating the value of germline testing in all GI oncology patients rather than using criteria-based testing. We were talking about whether you should just test everyone. I was in opposition to that plan, I was the person arguing that we should not be doing that and I outlined a number of arguments that I think are relevant in this setting.

I made the point that frankly no matter how much we've learned about how many patients will be positive when we test them for germline genetic mutations and that positive rate we know is going to be about 10 to 15 percent, that means that basically 85 percent of people who get testing are going to be negative. I think when we let criteria down and we just test everyone we're going to generate a lot of negative information that's frankly not going to be particularly useful and is going to be expensive. When we think about 355,000 new GI cancer cases a year in this country, and we ask the cost of germline testing at even a low rate of about 250 to 500 dollars a test, that's going to mean we're spending anywhere from 90 to 180 million dollars a year on testing individuals, most of whom are going to be negative. If you expand that testing even further and think about people who have survived colon cancer and are still living or patients who are living longer with colon cancer, that's going to give us upward of 1.5 million prevalent cases of colon cancer in the country. When you think about the costs of testing those individuals, we're going to be somewhere in the 500 million dollar range in terms of how much we're paying. So is this really a good investment for a lot of negative information? I think a corollary to that argument is that many of those results even though they are technically positive, they're actually positive for findings that have relatively minimal if no immediate implications for the patient sitting in front of you getting the testing. These are low-risk results, common polymorphisms, also recessive findings in genes that don’t actually have a meaning unless you have 2 copies. All of these things, even though in the papers that are written, tout these as being positive results, when you scratch beneath the surface, you find that these positive results don't actually necessarily always have that much clinical meaning. Just to sort of make a gross generalization based on the data, about half those results that you find, half of those 10% to 15%, are going to be findings that are not necessarily that relevant to the patient immediately. 

Another point, is testing someone with a new GI cancer at the time of diagnosis, is this really the right time to do this? I think we have to think for those who are not seeing GI cancer patients every day, these tend to be older patients, they tend to be very sick at the time of diagnosis, most are gonna die of their diseases within 3 to 5 years. This is a group that they're very focused on the time that they're getting this testing, they're focused on their treatment, they're focused on surviving and here we are introducing this additional level of testing that many probably don't even really want at that time but someone is just telling them "you should do this testing because it's part of your care.” I think that what we're ultimately doing is we're doing testing at our own convenience and we're giving information back to patients who don't necessarily want it at that time. Ultimately, the value of the hereditary genetic information is primarily not about guiding the patient’s care so much as it's really about having an impact on their family members and them being able to use this information to potentially go out and get testing and guide their own care. Frankly, that testing could be done at any time, it could be done even after the patient passes away, there are some theoretical advantages of doing it first, but I think the point being that it is a suboptimal time for a sick cancer patient to get testing, and I think that we're sometimes rushing people into having information generated that they really don't have good informed consent and information about. The research has shown that the group that actually is most disadvantaged by that approach are actually underserved patients, patients who have relatively modest genetic knowledge, who may not have great awareness of genetic tests, who are underserved, who are racial, ethnic minorities, so it's like the group that we should really be focusing the most attention on to take care of them and make sure they're really understanding what's going on, we're actually doing the poorest job and that's not great. 

Another point that was a corollary to that is that this argument that “well if you test the patient and you generate that positive result then family members are going to testing too,” in this model that's called cascade testing, meaning family members here that Auntie Jean has a mutation and so they're gonna go out and rush out and get tested for it. The reality is that's an utter myth, even though there are models that show that there's advantages to that and it's cheaper for society to do that, data from Memorial Sloan Kettering and a researcher that was published just in the past couple years show that actually the number of family members that get tested based on a positive result is really pretty modest and it's most modest and it's lowest again, in those underserved families because the information, the understanding that there's that that's where the advantage is is the poorest. We like to make this assumption that discovering this genetic risk is actually gonna sort of change the course of cancer risk in these families, but there is not a lot of data to support that that actually happens. 

Finally, the point that I think is really most important, that builds off that is that our goal in testing patients for hereditary risk should not be in generating a percentage to say, " we tested 100 patients and we found 15% of people are carrier and that's amazing we found 15%,” because that's really just an intermediate goal. Just telling someone they have a risk doesn't shift the needle of people dying from cancer in this country. What shifts the needle is actually making sure that that result number one, translates into potentially testing for family members or even anyone, more people getting tested understanding these risks are out there, but it actually translates into cancer prevention outcomes to the patient or their family members being able to better access, whether it's colonoscopy,mammography, MRI for the breast, patients adopting healthier behaviors, giving up cigarettes, smoking, things like that, that will ultimately have been proven to help people live longer. Just telling someone they have a mutation hasn't changed anything and frankly, what we see is a lot of people get this information and they don't actually do anything with it. We actually have to focus our energies less on the diagnosis and more on the effectiveness, which is kind of another word for making sure that information translates into a cancer prevention outcome.

Source: 

Hall M. Debate: Germline testing for gastrointestinal tumors for all irrespective of tumor origin: Yes vs no. Presented at Great Debates and Updates in Gastrointestinal Malignancies. May 17-18, 2024. New York, NY.