Northwestern blood test detects pancreatic cancer risk missed by standard tests

Scientists at Northwestern Medicine have demonstrated that a highly sensitive blood test can detect traces of pancreatic cancer missed by standard testing, potentially helping physicians identify patients whose disease is more likely to return even when scans appear reassuring.

The sensitive blood test focuses on KRAS, a genetic mutation that drives more than 90% of pancreatic cancers. This discovery comes as a new revolutionary drug targeting KRAS is showing substantial survival benefits and nearing FDA review.

According to Dr. Akhil Chawla, clinical associate professor of surgery at Northwestern University Feinberg School of Medicine and complex surgical oncologist at Northwestern Medicine, the ability to track this specific mutation is becoming increasingly important as KRAS-targeted therapies emerge.

"That combination could fundamentally change how we identify high-risk patients, monitor microscopic disease, and potentially intervene earlier before recurrence becomes clinically visible, ultimately getting more patients to cure,"

Dr. Akhil Chawla, clinical associate professor of surgery at Northwestern University Feinberg School of Medicine and complex surgical oncologist at Northwestern Medicine, via news.northwestern.edu

Pancreatic cancer is one of the deadliest malignancies. Even when diagnosed before it has visibly spread, many patients undergo months of chemotherapy and surgery, yet their cancer often returns. Dr. Chawla noted that in these patients, circulating tumor DNA levels are often extremely low and difficult to detect.

Comparing Detection Methods

The study, published June 30 in Clinical Cancer Research, followed 106 Northwestern Medicine patients with localized pancreatic cancer from diagnosis through chemotherapy and surgery. The researchers compared two types of "liquid biopsies"—blood tests that search for traces of DNA shed by cancer cells into the bloodstream.

One method, next-generation sequencing (NGS), is more commonly utilized because it searches for large numbers of cancer-associated genes simultaneously. The other, digital droplet PCR (ddPCR), searches for one set of genes at a time. In this study, the Northwestern team used ddPCR to focus specifically on the same KRAS mutations that are targeted by emerging drugs moving closer to FDA approval.

The difference in detection rates was stark. At diagnosis, the sensitive test detected signs of cancer in 65% of patients, compared to 17% using the standard test. This represents nearly four times as many patients as conventional next-generation sequencing tests (NGS), which are more commonly utilized.

The sensitive test continued to uncover residual disease after treatment when other methods failed:

Dr. Chawla stated that this suggests physicians may currently be missing residual disease in most patients using currently available testing approaches.

Impact on Survival Prediction

The researchers found that better detection meant better prediction of survival outcomes. The study identified a previously hidden group of high-risk patients whose cancer was missed by standard NGS but detected by ddPCR. This specific group survived a median of 27 months after diagnosis. In contrast, patients who tested negative on both tests survived a median of 41 months.

Because these tests rely on a simple blood draw, they can be repeated over time without requiring invasive procedures, providing an early sign that cancer is present or may return.

Context and Next Steps

While this tool offers a new path for monitoring, there is no standard diagnostic tool or established early detection method for pancreatic cancer in the general population yet. Most pancreatic cancer patients are diagnosed at stage IV. While surgery is the best option for long-term survival of pancreatic cancer and can increase a patient’s survival by about ten-fold for eligible patients, many are told they are ineligible.

Current pancreatic cancer surveillance programs study people at high risk due to family history, an inherited genetic mutation, new onset diabetes or chronic pancreatitis using imaging tests, blood or pancreatic fluids. However, blood tests alone cannot lead to a definitive pancreatic cancer diagnosis; additional tests, like imaging and biopsies, are necessary to confirm the diagnosis.

The Northwestern scientists collected blood samples for this study between October 2020 and October 2024. Dr. Chawla indicated that the findings must be validated in larger multi-center studies before ddPCR can be used routinely in pancreatic cancer care.