Mammograms are used to detect breast cancer early. Colonoscopy is available to detect colon cancer early. But there is no standard test to detect early cases of pancreatic cancer, before the cancer cells have spread and when surgery is more likely to help.
Early detection of pancreatic cancer can increase a patient’s chances of survival. Although the pancreas is responsible for approximately 3% of all new cancer cases in the United States, it is the third leading cause of cancer deaths and is expected to become the second leading cause of cancer deaths by the end of this decade.
In the United States, research teams are exploring ways to detect cases early, with many turning to blood-based liquid biopsy tests.
“This term ‘liquid biopsy’ essentially tries to find markers in the blood that indicate a tumor is present – and there are many different ways to do that. There are many different characteristics of a tumor that can end up in the blood that you could use,” says Dr. Brian Wolpin, director of the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute., whose laboratory has done work in this area.
But many studies examining the potential of liquid biopsy tests for the early detection of pancreatic cancer are still in their early stages. And the U.S. Preventive Services Task Force recommends against screening for pancreatic cancer in adults who have no symptoms, mainly because there is no established method or test to detect this form of the disease early in the general population.
Although there is currently no single recommended blood test to detect early pancreatic cancer, “there is a large scientific community trying to change this and find a screening test that we can use in the clinic, but it’s quite difficult,” Wolpin said. . “There is still more work to be done to get there.”
One team presented its research Monday at an annual meeting of the American Association for Cancer Research, describing the development of a liquid biopsy test found to detect 97% of stage I and stage II pancreatic cancers in hundreds of volunteers. The researchers come from the City of Hope Comprehensive Cancer Center and other institutions around the world.
Their research, which has not been published in a peer-reviewed journal, included 984 people, some healthy and others with pancreatic cancer, based in Japan, the United States, South Korea and China.
The researchers collected blood samples from each person and tested the expression of a series of small genes, called microRNAs, in the blood and encapsulated in exosomes found in the blood. Exosomes are small vesicles secreted into the blood by both cancer cells and healthy cells.
“Cancer cells tend to release many, many more exosomes compared to our healthy cells, because our healthy cells do not multiply as quickly as cancer cells,” says Dr. Ajay Goel, senior author of the study and chairman of the Department of Molecular Diagnostics and Experimental Therapeutics at City of Hope. “And once these exosomes are released by the tumor cells, they circulate in our bloodstream.”
Goel and his colleagues identified eight microRNAs found in exosomes secreted by cancer cells in the pancreas and five microRNAs in the blood. They used those markers to develop an approach to determine whether a person’s exosomes are associated with pancreatic cancer.
The researchers found that their liquid biopsy approach detected 93% of pancreatic cancers among the US volunteers in their study, 91% of pancreatic cancers in the South Korean cohort, and 88% of pancreatic cancers in the Chinese cohort.
The researchers ran their tests again and this time not only used their exosome-based markers, but also tested for a key protein called CA19-9, which is known to be associated with pancreatic cancer. When they combined their approach with CA19-9 testing, they were able to accurately detect 97% of stage I and stage II pancreatic cancers in US volunteers.
“That’s what we’re excited about: that this test not only worked beautifully at all stages, but is also 97% accurate in finding those who have stage I or stage II disease,” Goel said.
He added that the test produced false-positive results for stage I and II pancreatic cancer at a rate of less than 5%, the study data showed.
“It is very important to diagnose the disease at the earliest possible stage, such as stage I or II, which means there is a greater chance that the cancer will be surgically operable,” Goel said. “The best cure for a pancreatic patient is not chemotherapy or drugs, but removal of the cancer.”
Surgeons can be “very reluctant” to operate if someone has stage III or IV pancreatic cancer, he said. This is sometimes due to the complexity of such a procedure, the long-term complications, and the likelihood that surgery at an advanced stage may not be enough to prevent the cancer from returning.
“That’s why it’s very important that this blood test is so good that in 97% of cases it can detect the cancers at the earliest possible stage, where we can intercept the cancer, where we can intervene and we can surgically remove it. cancer effectively,” Goel said.
‘We have to do something’
There are blood-based tests for pancreatic cancer used in medicine, but these are often used in people who have already been diagnosed with the disease. Doctors may repeat blood tests during and after treatment to determine how the cancer is responding. But there is no blood test that can detect pancreatic cancer at an early stage.
Goel and colleagues wrote in their abstract that their approach “may be further validated for clinical use in the near future,” specifically for the early detection of pancreatic cancer.
“We were generally excited about this particular data because the type of cancer we’re looking at here is extremely deadly,” Goel said.
“The number of people affected by this disease or cancer will continue to rise,” he said. “So we have to do something about it, and that’s why we were extremely excited to have a blood-based liquid biopsy for the early detection of pancreatic cancer with this high sensitivity.”
The liquid biopsy test research that Goel and his colleagues presented is “interesting,” Wolpin said, and describes one approach to potentially developing a test for early detection — where there is a great need.
The final diagnosis of someone with pancreatic cancer may include a series of scans, blood tests and biopsies, which are usually not done until a person has symptoms including jaundice or yellowing of the eyes and skin, weight loss, abdominal or back pain or fatigue. and weakness. But by then the cancer is probably already advanced.
“The vast majority of patients with pancreatic cancer have advanced disease at the time of diagnosis. So 80% or more of patients have advanced disease where we know at the time of their presentation that it is very unlikely that we can cure the cancer,” Wolpin said.
“That’s very different from many other major cancers, such as breast cancer or colorectal cancer, where the vast majority of patients actually get sick at an early stage,” he said. “The symptoms of pancreatic cancer are generally less specific, such as abdominal pain or sometimes weight loss – things that often don’t immediately prompt people to see their doctor.”
But some experts warn that mass testing of healthy, average-risk people who show no symptoms could lead to false-positive results, causing more harm than good.
‘The pancreas is a very strange organ’
City of Hope researchers are not the only scientists hoping to develop a reliable test to diagnose pancreatic cancer patients as early as possible.
In 2020, a study from the University of Pennsylvania found that a blood test to screen for certain biomarkers linked to pancreatic cancer was 92% accurate in its ability to detect disease.
In 2022, a pilot study by researchers at UC San Diego and other institutions found that a blood test to detect proteins associated with cancer cells could identify 95.5% of stage I pancreatic cancers among a sample of more than 300 volunteers, including 139 were cancer patients and 184 were healthy people.
Overall, the field of pancreatic cancer is one where there hasn’t been much progress when it comes to early-stage or advanced-stage disease, said Dr. Al Neugut, a medical oncologist at Columbia University’s Herbert Irving Comprehensive Cancer Center and professor of cancer sciences. in epidemiology at the Columbia University Mailman School of Public Health, who was not involved in any research on liquid biopsy testing.
“Pancreatic cancer is an example of cancers that we have not achieved anything yet,” Neugut said.
“The pancreas is a very strange organ, and it’s just different from any other organ in the body,” he said. ‘It’s behind the abdomen, so difficult to reach. It’s not easy for a surgeon. It is not easy for an oncologist. In fact, it makes it very difficult to get closer. You cannot physically examine it. It is difficult to reach radiologically. It’s hidden.”
Although pancreatic cancer is rare, people can lower their risk by eating a healthy diet, maintaining a healthy weight, getting regular exercise, avoiding alcohol, limiting exposure to carcinogens and not smoking.
“Smoking is the leading preventable risk factor for pancreatic cancer,” according to the American Cancer Society.
Still, having some form of test to detect pancreatic cancer early would “dramatically change the landscape for patients,” Wolpin said, adding that he hopes the medical field can succeed in developing such a tool.
“The more patients we can find early, the better chance we have of curing patients of pancreatic cancer and of being able to reverse some pretty difficult statistics: almost 90% of patients who get pancreatic cancer die from their cancer,” Wolpin said. “We really need to change those numbers, and finding the cancer earlier would be a dramatic way to do that.”
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