Early Detection Test Options for Pancreatic Cancer

Kristie L. Kahl: What are the current early detection methods that we have available?

Diane Simeone: Early detection for pancreatic cancer is really a holy grail we have in the field. As a surgeon, I can tell you that I think that the early detection of pancreatic cancer is really critical for us to really push to have improved survival. It's very tough when patients come in with advanced disease and surgical treatment isn't really even on the table. We really put a big effort in place and in partnership with the National Pancrease Foundation to try to get information about what are the early detection tests that are out there.

Now, we currently don't have a perfect early detection test for pancreatic cancer. There are a lot of people that are working on developing and validating an early detection blood test for pancreatic cancer. I do think, based on the number and the high level of those efforts, that we're likely to have such a test in the next five years. There are different tests that are looking at circulating tumor cells in the blood, DNA from tumor circulating in the blood. There's another test that's being validated looking at an immune protein signature in the blood. And it might be that one of these tests comes forward as the best test. Alternatively, it might be a combination of these tests put together that work the best. And that is all now being evaluated with collaborative efforts of research institutions around the country in partnership with a number of foundations and the National Cancer Institute.

Importantly, if we develop an early detection blood test where we can pick up a pancreatic cancer, for example, that's a millimeter or two in size, we need to be able to find that tumor. And as a surgeon, if I see a patient who comes with a blood test and says, aha, there's a pancreatic cancer somewhere, but we can't see it on imaging, then our only recourse would be to remove the entire pancreas. So, when parallel to developing an early detection blood test, we need to develop more advanced and sophisticated modalities to image the pancreas, to be able to pick up that little tiny pancreas cancer. These are all things that are an evolution. But, you know, it requires coordination and obviously research funding to help propel those areas of research forward.

Kristie L. Kahl: What do surveillance programs consist of?

Diane Simeone: An important way to detect pancreatic cancer is to figure out who is at elevated risk and have sufficient elevated risk that they should be enrolled in a screening program. One of the important things that has been an advance is we've been able to develop guidelines that all patients with pancreatic cancer should get germline testing.

There's two points of value with that. One, is we know now that if someone has a pancreatic cancer that's associated with certain germline mutations and a BRCA mutation, they would be a perfect example. That actually changes how we treat that patient. It will drive us to give that patient a different set of therapies than we otherwise would.

Second, it helps us identify patients, family members, who should also get tested or should be put in a screening program. So really first making sure anybody who's got pancreatic cancer gets tested and we can identify family members at risk. We need doctors, when they see patients in the clinic as part of the routine physical exam, to do a thorough family history of cancer, and if that person has a family history of pancreatic cancer, to get them plugged in at a center that has expertise to really make sure that the appropriate patients get screened.

Kristie L. Kahl: What are the current costs of early detection screenings?

Diane Simeone: Screening carried out in the appropriate patient population, the cost will be much lower than the cost of identifying patients with advanced disease. A typical screening program is getting imaging of the pancreas annually. That'soften done with MRI, alternating on a yearly basis with a kind of test called an endoscopic ultrasound. The two tests are slightly different ways to look at the pancreas but are complimentary. If someone is in a screening program, we'll get a test once a year, or we can look at the pancreas in a detailed manner. And importantly, we encourage all patients who have family histories of pancreas cancer to be seen at centers that have expertise and that also do research in this area. Te only way we're going to push advances and understand better definitions of who's at risk is to do better risk modeling to identify new pancreatic cancer susceptibility genes for individuals at elevated risk to be seen at centers where that kind of activity is taking place.

Kristie L. Kahl: Can you also discuss germline testing and its role in early detection?

Diane Simeone: Germline testing is a critical part of screening and testing for individuals at high risk. It's surprising that germline testing is underutilized for patients at high risk. I see it all the time. I see individuals who have multiple family members with pancreas cancer that are seen by their doctor and no one has recommended that they get germline testing.

Germline testing is a simple blood test that is performed where DNA is isolated from the blood, and you can test for a battery of cancer susceptibility genes. Right now, we've identified about 15 genes that are associated with increased pancreatic cancer risk, and there are more to be found. The cost of these germline tests is relatively low. A high quality test can be done for as cheaply currently as $250. I'm sure that price will continue to drop. With the cost so low, we advocate that anyone who has a family history of pancreas cancer, please seek an expert opinion about whether a germline test should be done.

There are a couple of state projects that are offering germline testing routinely to the general population to look for cancer susceptibility genes. I do think that in the future, from a societal perspective, germline testing will be offered, potentially to all adults if they wish as part of their routine health care. If you find a cancer susceptibility gene like a BRCA gene or mismatch repair gene that can result in that person going on a screening program, that could change their survival. With screening, a lot of this can be preventable.

Kristie L. Kahl: Why are screening methods for those at an increased risk important to know about?

Diane Simeone: It's important to know if you're at an increased risk and should be screened because now we have good data that if you were to develop a pancreatic cancer, if you're in a screening program, the cancer will be found at a much smaller size. So, the ability for us to resect it surgically is much higher, such that most patients who are in a screening program that do develop a pancreatic cancer, over 90% of patients can have that tumor surgically resected. And that compares to the average patient who comes into a pancreatic cancer clinic, where only 15% of patients who present with a pancreatic cancer can have it resected. So that's a big game changer. We now have data that if you're in a screening program, the ability for us to remove that tumor with surgery is many fold higher. We are assembling the data now. That screening saves lives and that's where we want to go. And we want to make sure that everybody around the country that is at elevated risk knows what that risk is and is informed about whether they should be involved in the screening program.

Kristie L. Kahl: Should we be screening individuals who might be considered average risk?

Diane Simeone: It's important to realize that we're not advocating that everyone get their pancreas screened. We're not advocating screening of the general population. In general, we're advocating screening for people that have two or more family members with pancreas cancer; screening of people that have had a mother and father diagnosed with pancreatic cancer; and screening of folks who have a mutation that increases their risk of pancreatic cancer, in particular if they have had any family members with pancreas cancer. Individuals who have BRCA1 or BRCA2 mutation, or ATM mutations, or have other cancers like breast cancer, colon cancer and melanoma, your risk of pancreas cancer is higher. Wee want to make sure people know about those associations, and they get plugged in at the right place so that they're properly screened.

Kristie L. Kahl: If someone is not at risk for pancreatic cancer, is there any kind of early testing available right now?

Diane Simeone: There is not a universal early detection blood test for pancreatic cancer that's available. There are a number of groups and companies around the country and around the world that are trying to develop an early detection test for pancreatic cancer and cancer in general. Those research efforts are not mature enough that there's a test that should be used for the general population. But I expect in the next three to five years that these tests will become available. And obviously, depending on how the test performs – how sensitive and specific it is – that will determine how it should be rolled out as a testing tool.

Kristie L. Kahl: Since we don't currently have an early detection test for individuals who are not at risk, what can they still do to make sure that they understand their risk?

Diane Simeone: For all my patients, we talk about what are the modifiable risk factors for pancreatic cancer, and these are really important to know about. Smoking is probably the biggest risk factor for pancreatic cancer. Also, no heavy drinking. Light social drinking isn't associated with pancreatic cancer risk but heavy duty drinking, which is somewhere between two to three drinks a day can increase one's pancreatic cancer risk. We really want people to be very careful about alcohol intake, obesity and diabetes. These are pretty tightly linked with pancreatic cancer risk. In fact, if you look at the rise in pancreatic cancer over the last decade and look at the rise in type 2 diabetes and obesity, you can almost overlay those curves across the United States.

We really encourage patients to keep the extra weight off and make sure that you get your hemoglobin A1C checked every year by your physician to make sure that you don't develop new onset diabetes. There are other things that we talk to patients about, which I think there's some emerging data. Exercise, there's new data that really shows that exercise in general is helpful to mitigate cancer risk, not just pancreatic cancer, but frankly most cancers, and eating a healthy diet. These are things that are just, in general, good for your health, but good for your pancreatic health.

Kristie L. Kahl: What are the next steps in early detection testing?

Diane Simeone: We're at the cusp of developing an early detection blood test. I fully expect that that will be something available in the clinic in the next five years. Whether it's a sensitive or specific enough test to be used for the general population or more refined population at risk still remains to be determined. We are really pushing for improved imaging modalities to find small pancreatic cancers. Also, trying to better understand the link between diabetes in who has a new pancreatic cancer is important. About two-thirds of patients with pancreatic cancer will present with new onset diabetes. And we don't have a test that helps differentiate everybody that presents with diabetes, which is a large number of patients versus those who selectively present with a new pancreatic cancer. So, if we can develop a test and differentiate those two, all of these things are going to be game changers to improve survival for pancreatic cancer.