May 06, 2025
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and challenging cancers to diagnose and treat. More than 90% of pancreatic adenocarcinomas have KRAS mutations, one of the known initial drivers for cancer development. Mayo Clinic Hepatobiliary and Pancreas Surgery researchers recently shed light on the significance of mutant KRAS circulating tumor DNA (ctDNA) as a predictor of metastasis and survival in patients with PDAC.
The study, published in March 2025 in Annals of Surgical Oncology, involved nearly 800 patients, making it the largest study to date using ctDNA.
Sample analysis reveals advanced cancer risk
Researchers found that 20% to 30% of the patients with PDAC had mutant KRAS ctDNA detectable in their blood, peritoneum or both. Notably, patients without prior treatment exhibited the highest incidence of this mutation, suggesting that for optimal yield, ctDNA assays should be performed before any treatment.
Between 2018 and 2022, blood samples from 104 patients were analyzed, revealing that 14% KRAS ctDNA mutation. These patients were more likely to develop advanced, spreading cancer and had lower survival rates. Further testing of fluid from around the abdominal cavity in 419 patients showed similar results: 123 patients (29%) had the marker, correlating with worse outcomes.
The presence of this marker, whether in blood or abdominal fluid, indicated a poorer prognosis.
KRAS ctDNA testing enhances treatment precision and patient outcomes
These findings highlight the importance of incorporating KRAS ctDNA testing into the initial diagnostic process for PDAC. This test helps identify patients less likely to benefit from surgery alone, guiding treatment decisions toward chemotherapy or radiation before surgical intervention. For the approximately 10% of patients without KRAS mutation, the test is less conclusive, necessitating additional diagnostic measures.
"Historically, it’s been known that KRAS mutations are associated with more biologically aggressive pancreatic cancer," says Jennifer L. Leiting, M.D., a hepatobiliary and pancreas surgeon at Mayo Clinic in Rochester, Minnesota, and the study's first author. "This large study provides a clearer understanding of how to interpret test results and use them to improve patient care. It allows for more-accurate staging at diagnosis, leading to better treatment decisions."
The study underscores the potential of KRAS ctDNA testing to improve patient outcomes by enabling personalized risk stratification and effective treatment planning. "This improved diagnostic capability offers hope for patients and their families facing this challenging disease," says Mark J. Truty, M.D., M.S., a hepatobiliary and pancreatic surgical oncologist at Mayo Clinic in Rochester, Minnesota. Dr. Truty is a senior author on the study. "Our team is optimistic to see how advances in genetic testing are directly benefiting our patients," he says.
As pancreatic cancer experts continue to seek better ways to diagnose and treat PDAC, the incorporation of KRAS ctDNA testing represents a significant step forward. By identifying patients at higher risk of metastasis, this test can guide more-informed treatment strategies, ultimately improving patient outcomes.
For more information
Leiting JL, et al. Molecular KRAS ctDNA predicts metastases and survival in pancreatic cancer: A prospective cohort study. Annals of Surgical Oncology. In press.
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