CA19-9 Plus Liquid Biopsy Represents Diagnostic Biomarker of Interest for Early-Stage Pancreatic Cancer Detection

CA19-9 in combination with an exosome-based liquid biopsy has shown potential as a diagnostic biomarker for early-stage pancreatic cancer, prompting investigators to further examine it in the ongoing prospective PANXEON study (NCT06388967), according to Ajay Goel, PhD, AGAF.1

During the 2025 Gastrointestinal Cancers Symposium Goel presented data from a prior multicenter cohort study published in Gastroenterology which demonstrated that CA19-9 alone yielded an under the curve (AUC) of 0.88 with respect to disease detection in patients with any-stage pancreatic ductal adenocarcinoma (PDAC) and 0.86 in stage I and II PDAC.1,2 When combined with the exosome-based liquid biopsy, these AUC values rose to 0.99 and 0.99, respectively. These data led to the initiation of PANXEON, which is aiming to further validate the approach in an international prospective trial.

“Pancreatic cancer is a very lethal [disease], but the incidence is not very high, so we don’t typically screen for it in the general community,” Goel said in an interview with OncLive®. “Most patients who are initially diagnosed with pancreatic cancer have disease which is already advanced, which means they cannot be surgically treated. If you can’t surgically remove the cancer, the prognosis is not very good. If we can find it early, we can surgically treat it, save some of these lives, and help [a portion] of these patients live longer. That’s where the need for noninvasive diagnostics comes in.”

Goel is a professor in and the chair of the Department of Molecular Diagnostics and Experimental Therapeutics at City of Hope in Duarte, California.

In the interview, Goel discussed the current landscape of biomarker testing for early-stage pancreatic cancer, the potential of CA19-9 in this area, and the next steps for the development of a CA19-9-based test.

OncLive: What are the limitations of the current biomarkers in pancreatic cancer and have any shown potential for early detection?

Goel: The best biomarker we currently use in the clinic is CA19-9; it’s a marker which we use for most patients with pancreatic cancer. That marker is best for prognosticating patients or monitoring response to certain treatments, but it’s not a very good diagnostic marker because it lacks adequate sensitivity and specificity.

There are several commercial tests which are currently in different phases of study. But most of them have the same challenge in that they work fairly well, but only in patients with stage III or IV disease. But if the goal is finding early-stage cancers, meaning stage I or II disease, there’s no good marker out there. That’s what the focus of our work has been, to develop markers which can find this disease as early as possible. We’re very excited that we now potentially have a blood test which can help us achieve that goal.

What are the most important characteristics for noninvasive biomarkers to have in order to improve early detection of pancreatic cancer?

[Pancreatic cancer] is not very common and the test has to have a very high degree of sensitivity and specificity. If the test is not very sensitive, we are going to miss the disease. Pancreatic cancer surgery is very complex. We can’t put [noneligible] patients through pancreatic surgery to remove their pancreas, because they could potentially have other metabolic disorders once they lose their pancreas.

The biggest barrier [to an effective test] is [that it needs] to have a very high degree of sensitivity, more than 95%, and 95% or above specificity to be sure that the patient we are going to treat, whether surgically or with other alternatives, has pancreatic cancer before we put them on an operating table.

What is the design of the PANXEON study and have any data been reported using the CA19-9 plus liquid biopsy approach?

We [are performing] a multi-institutional, multinational case-controlled study which includes [approximately] 1500 patients and healthy subjects [who] were enrolled at 7 sites in the US, 2 in [South] Korea, 2 in Japan, and 1 in China. We have this large cohort where we have tested the performance of the assay to see how well it can discriminate between people without disease and those who have [PDAC].

We have found that the blood test on its own can [identify] 91% of cases that are stage I or II PDAC. But when we combine this assay along with CA19-9, the accuracy of the test goes up to 97% for stage I/II disease, which is quite exciting. We are looking forward to continuing to build upon this evidence.

What are the future directions for this research?

We are actively licensing this technology to biotech and pharmaceutical companies, and they will do independent clinical trials to truly validate the performance of this test in a general, high-risk population. Since pancreatic cancer is not very common, we cannot run it on the [whole] population. It has to be run on patients [who are] high risk, meaning those who have either family history, a certain mutational risk, chronic pancreatitis, or new onset diabetes. These are all the high-risk groups we need to test, which we have not done yet. If we can show that this blood test works as well as we think, then we hope in the next few years it will probably be available in the market [for use in] high-risk individuals.

References

1. Goel A. Noninvasive biomarkers for the early detection of pancreatic cancer. Presented at: Gastrointestinal Cancers Symposium; January 23-25, 2025; San Francisco, CA. Presentation 3.
2. Nakamura K, Zhu Z, Roy S, et al. An exosome-based transcriptomic signature for noninvasive, early detection of patients with pancreatic ductal adenocarcinoma: a multicenter cohort study. Gastroenterology. 2022;163(5):1252-1266.e2. doi:10.1053/j.gastro.2022.06.090