HBF Spotlight: Randall E. Brand, MD

Meet Dr. Brand!

Dr. Brand is a gastroenterologist and Professor of Medicine at the University of Pittsburgh
School of Medicine in the Division of Gastroenterology, Hepatology and Nutrition.
He is the academic director for the GI Division at the University of Pittsburgh Medical Center (UPMC) Shadyside Hospital, directs UPMC's GI Malignancy Early Detection, Diagnosis, and Prevention Program, and leads UPMC’s Hereditary GI Tumor Clinic.
Dr. Brand is widely respected for his work in the early detection of pancreatic cancer, hereditary GI cancers, and pancreatic cystic lesions. He also serves as a principal investigator in the Early Detection Research Network and Pancreatic Cancer
Detection Consortium, while participating in NCI-, NIH-, and DoD-funded research projects focused on the early diagnosis of pancreatic cancer.

Why is early detection of pancreatic cancer so difficult compared to other cancers?
What are the main limitations of current screenings approaches?

Screening refers to evaluating an organ for cancer in the general population. However, pancreatic cancer is not common enough to justify screening everyone, unlike colon cancer. Doing so would result in a large number of tests with low yield, exposing patients to unnecessary risk and representing a poor use of healthcare resources.

Decades ago, it was recognized that screening the general population for pancreatic cancer was not effective, so the focus shifted to high-risk individuals. Typically, these are individuals with a lifetime risk of at least 5 to 10% for developing pancreatic cancer, compared to about 1.7% in the general population today.

In 2026, patients who are candidates for surveillance either have a genetic predisposition to pancreatic cancer or are members of what is termed a “familial pancreatic cancer kindred.” Genetic risk is associated with known pathogenic variants (mutations) in genes linked to increased pancreatic cancer risk, most commonly ATM and BRCA mutations. Familial pancreatic cancer kindred refers to families with multiple cases of pancreatic cancer, involving at least two directly related individuals. In these cases, candidates for surveillance are also directly related to an affected family member, in the absence of a known genetic mutation.

Another challenge is the location of the pancreas, as it’s in the middle of the abdomen and not easy to see, feel, or touch. By the time people develop symptoms and get diagnosed with pancreatic cancer, it’s usually later because of symptoms being nonspecific.

For these high-risk individuals, how effective is current surveillance and are there any limitations?

There are several challenges with surveillance for pancreatic cancer. The goal has been to detect cancer when it is small and confined to the pancreas, as it tends to spread early. To achieve this, annual imaging of the pancreas was recommended. CT scans are generally avoided due to repeated radiation exposure, which may increase long-term cancer risk. Instead, the two primary approaches used are endoscopic ultrasound and MRI.

Endoscopic ultrasound (EUS) involves sedation and the use of a specialized endoscope with an ultrasound probe, allowing detailed visualization of the pancreas from the stomach and small intestine. If an abnormality is identified, a biopsy can be performed. While generally safe, a biopsy carries a risk of pancreatitis.

MRI is an imaging test that is particularly useful for detecting pancreatic cysts. Advances in MRI technology over the past several decades, including improved machines, imaging, and sequencing, have enhanced its ability to visualize the pancreas, though the use of contrast is typically required with MRI scans. Additionally, many centers alternate between EUS and MRI on an annual basis.

Despite this established surveillance strategy, there are still important uncertainties regarding its effectiveness. The strategy was developed in the first place based on expert consensus, with the goal of detecting tumors earlier, but several factors remain unclear. One key question is whether this approach allows for earlier detection of the tumor, meaning identifying cancer when it is still confined to the pancreas. In the general population, only about 10 to 15% of pancreatic cancers are diagnosed at stage one, while over half are diagnosed at stage 4. Another important question is whether detecting cancer at stage one actually improves outcomes or leads to cure.

Because of these uncertainties, we recommended surveillance at specialized centers participating in research registries. These registries allow for tracking outcomes over time to determine whether early detection strategies are effective. Two of the most prominent registries include the CAPS Consortium, led by Johns Hopkins University with other participating universities including our center at the University of Pittsburgh, and the more recently established PRECEDE Consortium, which includes over 65 sites nationally and internationally.

Data from the CAPS Consortium helps illustrate both the potential and limitations of surveillance. In a study published by our consortium in 2022, 1,461 high-risk individuals with an estimated lifetime risk of at least 5% were followed from 2015 to 2021, most for the full six years with annual imaging. During this period, we were able to identify 13 pancreatic cancers, particularly 10 invasive and 3 high-grade dysplasia (non-invasive abnormal cells) cases. Although this number of cases seems small, it is higher than what would be expected if you randomly picked 1,461 people instead.

Most importantly, 75% of these 13 cases were detected at stage one or earlier, demonstrating a “stage shift,” compared to only 10 to 15% of pancreatic cancers diagnosed at stage one in the general population. However, even with earlier detection, patients still died from pancreatic cancer, though we did observe improved five-year survival rates. Overall, we have not been able to prove survival benefits. At this time, we don’t have enough patients using our strategy. Instead, surveillance provides more patients the opportunity for cure.

Ultimately, what we are finding earlier is only part of the picture. Our oncology and surgical oncology colleagues are also working on better treatments and approaches. In addition, with targeted therapies and personalized treatment approaches, particularly in hereditary patients with BRCA mutations or Lynch syndrome, there are targets that can make these cancers more susceptible. The issue isn’t that the stage one disease surgery wasn’t done well, rather the problem is that microscopic spread may already be present. Therefore, what we need are better treatments to address that microscopic spread.

It does make sense that if patients don’t present with significant weight loss or cancer that has visibly spread throughout the body, the immune system and these therapies will work better to mop up remaining cancer cells. We have seen this in other cancers, such as colon cancer, where improved treatments have led to better outcomes, even in more advanced stages. Continued progress will depend on developing more effective treatments, which are currently being studied for pancreatic cancer.

What are the most promising developments in early detection currently, particularly with respect to
blood-based biomarkers and your recent work in this area?

A lot of my career has focused on blood-based biomarkers. If we go back to the study involving 1,461 high-risk patients, it’s clear that we are over-screening this group. From a practical standpoint, over six years of follow-up, only 13 cases of pancreatic cancer were identified. This highlights the need for better ways to distinguish who is high-risk and low-risk within this group. I think that blood-based biomarkers will play an important role in that.

I also think we have to flip that data around from this study, as around 25% of the time, despite annual imaging, tumors were still found beyond stage one. So if we had a blood test used between annual surveillance, it might improve our chances of identifying cancer at an earlier stage, particularly stage one, rather than waiting the full year. On the other hand, if we had a test with a very strong negative predictive value, it may allow patients to go every other year for an invasive test and rely more on blood tests to follow them.

We also have to be realistic. It’s well recognized that at most, 10% of the patients who develop pancreatic cancer have a hereditary or genetic predisposition. We also know that about 15% will have cysts in their pancreas, but the majority of patients are not candidates for surveillance currently. I'm still not suggesting that the general population be screened, but people are using AI and other approaches to better identify individuals at higher risk and move them into that 5 to 10% lifetime risk group. We’re not going to be able to screen everyone initially with MRI or endoscopic ultrasound, so having other tests, like blood-based tests, may help enrich the population. Even though I do a lot of research in 6 this area, I’m not endorsing any of the current blood tests until we better understand how to apply them in clinical practice.

This is not unique to pancreatic cancer. Many of the blood tests being developed now are aimed at detecting multiple cancers, what we call multiple cancer early detection (MCED) approaches.

For the general public, what would you say is the most important message when it comes to pancreatic cancer and early detection? With that, have you come across any misconceptions that people have, particularly those without a medical background?

Firstly, we are dealing with a vulnerable patient population. The vast majority of patients have only seen their loved ones or friends die of pancreatic cancer. We need more survivors, which is why I’m in this field.

The second point is that, in truth, if you're going to do surveillance, it's not like a colonoscopy where you do one and then you wait five years, or follow a different interval depending on risk. It's really a commitment to annual imaging right now, in 2026, that gives you that opportunity for a cure.

I would encourage patients to go to centers that are at least participating in some form of research or registries, because we need to better refine our approaches and strategies to surveillance. This can only be done with patients giving us the gift of knowledge from getting their routine annual imaging, which is recommended regardless, but also participating in research studies, which would be of tremendous help.

So my most important message to the general person is just because you may be considered high risk, chances are you still won't develop pancreatic cancer. That risk is not zero as you are higher than average, but we don’t have a way of predicting which individual will develop it.

My biggest fear is that individuals may just show up to start screening. I review each case and I think anyone who does surveillance should be doing the same thing, going over the risks, benefits, and limitations so that people understand the misconception that a negative screening test means everything is great. I don’t know that and I have to always be honest. That’s why we’re watching patients annually. I think it’s great and we’re hoping this approach works, but it isn’t perfect, and we’re trying to make it better.

But I think that's a point that sometimes gets overlooked by the patient because they like to think everything is fine and I get that. We do not recommend screening most cancers in the general population, but for some cancers, like ovarian cancer in high-risk individuals, most commonly due to BRCA1 or BRCA2, we may recommend risk-reducing surgery at the appropriate age to remove the ovaries. You really can’t do that in the pancreas right now, because that would make you a brittle diabetic, and there’s a small risk of death from the surgery, even in the best hands.

So while the numbers are low as discussed, 13 cases out of 1,461 patients, it doesn’t mean that you’re going to develop pancreatic cancer, but we can’t tell which individual will. So right now, we need to follow people closely.

Are there any resources for patients that you would recommend?

To me, the three major sources that people could turn to are: the National Pancreas Foundation (NPF), Pancreatic Cancer Action Network (PanCAN), and the PRECEDE Consortium. The PRECEDE Consortium is particularly important for individuals who are concerned about whether they may be candidates for surveillance, as sites are located throughout the country and can help point patients in the right direction for one-on-one discussions.

Keep in mind, unlike other cancers in hereditary syndromes such as BRCA2, where you see early-onset breast or ovarian cancer, the age at which pancreatic cancer develops tends to be only a year or two younger than the average in the general population, which is the late 60s. Because of this, we don’t usually begin screening until around age 50, or 10 years younger than the youngest case of pancreatic cancer in the family for most syndromes. There are a few cases where we may start earlier, but in general this is the approach.

I think that patients shouldn’t be overly concerned about screening or surveillance in their 30s and 40s. At the same time, they should keep in mind that lifestyle factors matter. For example, they shouldn’t smoke, eat a healthy diet with fruits and vegetables, and maintain a healthy weight. The ultimate goal is to mitigate risk factors as much as possible

All of us at HBF thank Dr. Brand for his innovative and breakthrough approaches to solving the toughest cancer challenges. Importantly, his commitment and support of this Foundation’s mission of recognizing and supporting early career cancer researchers has been, and continues to be, truly appreciated.