Mayo Clinic Researchers Identify a Measurable Genetic Mutation as a Significant Predictor of Metastasis and Survival in Pancreatic Cancer

A new study by Mayo Clinic Comprehensive Cancer Center researchers found that the presence of a specific genetic mutation — KRAS circulating tumor DNA (ctDNA) — strongly indicates a higher risk of cancer spread and worse survival rates for patients with pancreatic ductal adenocarcinoma (PDAC). The mutation was identified using a readily available and clinically approved blood and abdominal fluid test.

PDAC is an aggressive form of cancer that is often difficult to diagnose. Most patients already have cancer spread to other parts of their body when initially diagnosed, and current tests often miss this hidden spread. This makes it challenging to determine the best treatment strategy. The findings, published in the Annals of Surgical Oncology, may help identify patients who are more likely to have cancer spread to other parts of the body, therefore providing doctors and patients with the right information to make informed decisions about treatment.

"This is a major advancement for pancreatic ductal adenocarcinoma," says Mark Truty, M.D., hepatobiliary and pancreatic surgical oncologist within Mayo Clinic's Department of Surgery. Dr. Truty is senior author of the study. "We've had this genetic testing available for a number of years, however, we did not know the significance of the results or how to interpret them. Having the KRAS status will allow the patient and their provider to make better decisions about their individual cancer treatment."

The prospective cohort study, involving nearly 800 patients — the largest patient series to date in the literature using ctDNA — found that 20%-30% of patients with PDAC have detectable mutant KRAS ctDNA in the blood and/or peritoneum, and that those without any previous treatment, such as chemotherapy, had the highest incidence. Thus, the study suggests that ctDNA assays should be performed prior to treatment to have the highest yield.

The researchers examined data between 2018 and 2022. Blood sample tests revealed that 104 patients (14%) had KRAS ctDNA mutation. These patients were more likely to develop advanced, spreading cancer and had a lower survival rate. Further testing of fluid from around the abdominal cavity in 419 patients showed similar results: 123 (29%) had the marker, and these patients also experienced worse outcomes. The presence of this marker, whether in blood or abdominal fluid, indicated a poorer prognosis.

The study highlights that while surgery is the only known cure, most patients experience cancer spread after surgery. The test helps identify patients less likely to benefit from surgery alone, guiding treatment decisions towards chemotherapy and/or radiation before surgery. For patients without the KRAS mutation (approximately 10% of cases), the test is less conclusive and other tests are needed.

"Historically, we've known that KRAS mutations are associated with a more biologically aggressive pancreatic cancer," says Jennifer Leiting, M.D., hepatobiliary and pancreatic surgeon within Mayo Clinic's Department of Surgery. Dr. Leiting is first author of the study. "But this large study gives us a much clearer understanding of how to interpret the test results and use them to improve patient care. It allows for more accurate staging at diagnosis, leading to better treatment decisions."

The researchers suggest that this test should become a standard part of the initial diagnosis for PDAC, enabling more personalized risk stratification and effective treatment plans.

"This improved diagnostic capability offers hope for patients and their families facing this challenging disease," says Dr. Truty. "It's optimistic to see how advances in genetic testing are directly helping our patients."

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Designated as a comprehensive cancer center by the National Cancer Institute, Mayo Clinic Comprehensive Cancer Center is defining the cancer center of the future, focused on delivering the world's most exceptional patient-centered cancer care for everyone. At Mayo Clinic Comprehensive Cancer Center, a culture of innovation and collaboration is driving research breakthroughs in cancer detection, prevention and treatment to change lives.