Young-Onset Diagnoses Continue to Rise in Pancreatic and Biliary Cancers


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Alok A. Khorana, MD, discusses on-the-rise pancreatic and biliary cancer rates in younger patients, plus the rationale of potential future research into the role of the gut microbiome in these patients.

Alok A. Khorana, MD

Alok A. Khorana, MD

Although rates of patients diagnosed with pancreatic cancer and biliary cancer continue to rise, a disproportionate increase has been seen in younger patients. Researchers postulate that this increased incidence may be due to lifestyle changes including lack of access to healthy food, obesity, and increased use of antibiotics, all of which can influence the gut microbiome, according to Alok A. Khorana, MD.

In data presented at the 2022 ASCO Annual Meeting from a retrospective cohort study of 360,764 patients diagnosed between 2004 and 2017, the number of patients with young-onset pancreatic or biliary cancer increased by 33.3% during the study period, and the risk for stage IV disease (6.4% of all patients) was higher than that of stage I-III disease (5.4% of all patients; odds ratio, 1.25; 95% CI, 1.21-1.29).

Rates of incidence in the young-onset population were more common in males, African American patients, and patients with lower income. Khorana explained that the root of the increase in young-onset pancreatic and biliary cancers still needs to be further explored.

“We need to drill down more into understanding risk factors, and the fact that many of these patients presented at a more advanced stage [is troubling],” Khorana said. “At this point, we still need to figure out what etiologic factors are driving this. In colorectal cancer [CRC], we’ve shown that the gut microbiome—the microorganisms that line the gastrointestinal tract—may be different in younger patients vs older patients, and we’re working to see if that’s also the case in pancreas and biliary cancers.”

In an interview with OncLive®, Khorana, a professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, the Sondra and Stephen Hardis Chair in Oncology Research, the vice-chair for Clinical Services of the Taussig Cancer Institute, and the director of the Gastrointestinal Malignancies Program at the Cleveland Clinic, discussed on-the-rise pancreatic and biliary cancer rates in younger patients, plus the rationale of potential future research into the role of the gut microbiome in these patients.

OncLive®: Could you expand on the rationale for investigating the rates of pancreatic and biliary cancers in younger patients?

Khorana: It’s well known that CRC is becoming more common in younger patients, but what we investigated in this specific project was whether pancreatic cancer and biliary cancer are also [becoming] more common in younger people than they used to be. We investigated a large national database of several thousand patients, looking to see if rates of young-onset pancreas and biliary cancer had changed over time. Unfortunately, what we’re finding is that the rates have gone up by about 30%.

What methods were used to conduct this research?

This was primarily a retrospective cohort study. We took data from the National Cancer database and analyzed it over a set period in the past decade. We examined rates of young-onset pancreas and biliary cancer by year, following trends. In general, pancreas and biliary cancers have increased, but the increase was [evident] in the younger population.

Unfortunately, that’s what we are seeing in our clinic these days. We see people who are in their 40s or mid 30s with a new diagnosis of pancreas and biliary cancer. This is a topic that deserves more attention.

What data were presented at the 2022 ASCO Annual Meeting?

We identified a 33% increase in the rate of young-onset pancreatic cancer and biliary cancer. This is in the context of a large increase in the incidence of pancreas and biliary cancers regardless of age. But the fact that rates are increasing in younger patients is troubling.

We don’t fully understand why. We did find that patients who are minorities, such as African American patients or Hispanic patients, had a disproportionately higher rate of increased incidence, but the majority of patients with [young-onset pancreatic or biliary cancer] are primarily White. Although [the increased rates] appear in patients who are African American or Hispanic, it’s still present across all races. We need to understand why that’s happening.

You mentioned some underrepresented populations have a higher likelihood of receiving a pancreatic or biliary cancer diagnosis. Why might this be?

We don’t quite know. It may be driven by gut microbiome, which is important for other types of young-onset cancers. It may be driven by lack of access to healthier food, fresh produce, and more balanced diets. For example, obesity rates are higher in some of these [underrepresented] populations. It may be related to obesity, lack of exercise, or more exposure to smoking and alcohol. We don’t fully understand these findings, but that’s what we need to work on to try to better figure out.

Why do you believe that we are seeing younger patients with cancers typically associated with older patients?

In general, there’s been a big change in lifestyle for all people over the past several decades. We see, especially in children that were born in the 1970s, 1980s, and 1990s, that there has been an increasing use of antibiotics in younger children and more obesity in younger people. There’s a lack of access to balanced diets among younger people. All these factors can influence the gut microbiome.

We think that’s how this is playing out, and as more emphasis [is placed] on plant-based diets, we hope that these trends will change. But for right now, every year that we examined had an increase in incidence in younger patients with pancreatic cancer. It is a worrisome trend, and we need to drill down further into why this is happening.

Could you expand on the importance of studying the gut microbiome in patients?

Microbiomics is the science of trying to understand the microorganisms that live in our body. We think of a body as ours but it’s actually made up of millions of microorganisms that happily live with us. They are good for us in terms of helping digest foods but also may alter our brain function, alter our gut function, and even reduce or increase our risk of cancer. This is a science that’s only been developed in the past decade or so.

The findings suggest that alterations in the gut microbiome can sometimes be bad for people in terms of increasing the risk of cancer. But that does not mean that there’s a certain microorganism that’s bad. [Rather, patients could have] a microbiomic profile that correlates with cancer. The biggest question is if we eat a better diet, have a better lifestyle, strive toward healthier living, and make these changes, will the microbiome profile revert to [lowering the risk] of cancer? Will that affect these increased young cancers that we’re seeing?

What are the next steps for research in this space?

We are funded to study the gut microbiome in patients with pancreas and biliary cancers. We’ve already shown that bile, the fluid that most people would consider sterile, does contain microorganisms. We are working hard to figure out if diet and lifestyle changes can influence the tumor microbiome of patients with pancreas and biliary cancers. Moreover, can these changes be reversed with interventions?

Why is it important to evaluate younger patients for these cancers?

Physicians should be much more aware of the possibility that younger people can develop cancers that we previously thought were for older people only. This can include CRC, pancreas cancer, or bladder cancer. All these cancers can occur in 30-, 40-, and 50-year-olds.

Sadly, many patients are turned away by their physicians because their symptoms are ascribed to something else, such as irritable bowel syndrome or inflammatory bowel disease, and they are not fully investigated because cancer is very low in the differential [diagnosis]. That may have been accurate a couple decades ago, but in this era, where we’re seeing this increasing emphasis on young-onset cancers, it’s important to ensure that younger people are evaluated for cancer, just as they would be if they were older.


Jayakrishnan T, Kamath SD, Nair KG, et al. Comparison of characteristics and outcomes of young onset versus average onset pancreatobiliary adenocarcinoma. J Clin Oncol. 2022;40(suppl 16):10522. doi:10.1200/JCO.2022.40.16_suppl.10522

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