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One of the reasons that pancreatic cancer is such a challenging disease is that it is frequently diagnosed once it’s reached more advanced, aggressive stages. The best opportunity for a positive outcome is when pancreatic cancer is diagnosed early, when the patient might be eligible for surgery.
The following is a Q&A to better explain the current state of pancreatic cancer research focused on early detection, and the process by which a novel early detection tool needs to be tested and proven effective.
How is pancreatic cancer currently diagnosed?
There is no standard diagnostic test for pancreatic cancer; however, there are multiple imaging techniques that are used to detect the disease, including specialized types of ultrasound, CT scan, and MRI. In a process called a biopsy, a small piece of tumor tissue is removed and examined under a microscope to definitively diagnose pancreatic cancer.
Scientists are working to develop a simple blood or urine test that could be used to screen many people and identify those who should be further examined by these imaging techniques because they may have very early stages of pancreatic cancer. In order to achieve this, many studies are devoted to identifying compounds in the blood or urine, called biomarkers, that could be useful in the diagnosis of pancreatic cancer. One of the biggest challenges facing these scientists is to find people who have very early-stage pancreatic cancer to test if the biomarker works. Several groups of scientists are examining individuals who are at high risk for developing the disease, including those with a strong family history of pancreatic cancer, as a way of testing whether any of these biomarkers are useful for detecting pancreatic cancer at early stages.
What is a biomarker?
A biomarker is a substance found in the body that can be measured. The amount of a biomarker may vary between a healthy individual and someone with a disease, therefore potentially aiding in diagnosis of that disease. In addition, biomarkers can sometimes be used to predict a patient’s response to a specific treatment, or to monitor whether a treatment is effective in a particular patient.
A recent review article in a biomedical journal found that more than 2,000 studies have been published evaluating more than 2,000 genes as potential biomarkers for pancreatic cancer. However, the only biomarker currently approved by the Food and Drug Administration (FDA) for use in pancreatic cancer is called CA19-9 (serum carbohydrate antigen 19-9). But, large-scale studies have shown that measuring CA19-9 levels is not useful for screening high-risk individuals or diagnosing pancreatic cancer. Instead, in patients whose tumors express the CA19-9 biomarker, levels can be monitored and may indicate whether a patient is responding to a treatment and whether the disease has recurred.
How do you determine whether a biomarker will work?
In order to become an FDA-approved pancreatic cancer biomarker that can aid in the diagnosis of the disease, rigorous experimentation is necessary. First, scientists in a laboratory analyze samples (can be blood, tissue, urine, pancreatic juice, or others) from pancreatic cancer patients to determine if there are genes, proteins, or other markers that are expressed in these patients, but not healthy individuals. A candidate biomarker has to be consistently and accurately measurable and there has to be a statistically significant difference in expression levels between specimens from pancreatic cancer patients and healthy individuals. One gene or protein is not usually enough to be sufficiently accurate – some tests now involve using several biomarkers to reduce the chance of getting false negative or false positive results and improve the value of the test.
Next, it is necessary to validate the potential biomarker in a larger number of samples in a retrospective manner. Retrospective means that the researchers are looking at samples from people who have already been diagnosed with pancreatic cancer. Again, it’s important that the biomarker can be consistently measured and always shows a significant distinction between pancreatic cancer cases and healthy individuals.
Once the biomarker (or panel of several biomarkers) has shown success in retrospective analyses, it’s necessary to undergo prospective, or forward-looking, studies. In order to be considered a viable diagnostic biomarker, it would have to accurately identify disease at early or precancerous stages. This type of study would take place as a formal clinical trial. People eligible for the trial would be those considered at high risk for developing pancreatic cancer. These people would be monitored to see if they develop the disease. It would take a large number of participants to allow for a significant enough subset of people to go on to develop the disease. Therefore, people would have to be watched and monitored over the course of many years.
These types of studies are expensive and time-consuming. While other biomarkers have been validated for use in the diagnosis of other cancer types, the pancreatic cancer field is still searching for a biomarker (or biomarkers) that could identify people with early stages of the disease. There are studies underway at various steps in the process of validating biomarkers. One of the furthest along is the CAPS (cancer of the pancreas screening study) taking place primarily at Johns Hopkins University, that is partially funded by the Pancreatic Cancer Action Network Inaugural Research Acceleration Network (RAN) Grant in memory of Skip Viragh. Although progress has been made, it will still be several years before the biomarkers being evaluated in the CAPS study could be considered validated for pancreatic cancer, and eligible for FDA approval. Other biomarker studies are also progressing nicely towards becoming novel early detection methods for pancreatic cancer.
What’s next?
Overall, it is a complex process to discover biomarkers that can aid in the diagnosis of pancreatic cancer. After identifying candidate biomarker or biomarkers, researchers must make sure that they are consistently measurable and clearly differentiate pancreatic cancer cases from healthy individuals. Then they must test the biomarker(s)’ accuracy in a large group of people already diagnosed with pancreatic cancer, compared to healthy individuals. The final step of this process, a prospective clinical trial, is the most arduous and, unfortunately, where most candidate biomarkers do not succeed. Even the only FDA-approved biomarker for pancreatic cancer, CA19-9, has failed to be an accurate indicator of early disease. Brilliant scientists and clinicians across the US and the world are working tirelessly to identify and validate biomarkers that could aid in the earlier diagnosis of pancreatic cancer.
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