Pancreatic cancer is not a disease that reveals itself easily, at least not initially. The pancreas is tucked deep in the abdomen, behind the stomach, so tumours aren’t easy to see or feel. A person might experience gastrointestinal distress, nausea, back pain, weight loss or fatigue — all symptoms that can be caused by a variety of conditions, most of which are much more common than pancreatic cancer.
By the time an individual develops symptoms that are worrisome enough to prompt a visit to a physician, such as dark urine or pale stools, the cancer has often spread. In four out of five people diagnosed with the disease, the cancer has spread beyond the pancreas and surgery is no longer an option. Once the disease has metastasized, it is almost always deadly. The five-year survival for people with stage four pancreatic cancer is just 3%.
Nature Outlook: Pancreatic cancer
Catching pancreatic cancer early is paramount — and can save lives. In one study1, individuals at high risk of developing the cancer received yearly computed tomography (CT) imaging, endoscopic ultrasound or magnetic resonance imaging (MRI), to look for the disease. Over 23 years, 26 of around 1,700 people in the cohort that underwent surveillance developed pancreatic cancer. Compared with about 1,500 people in a cancer database, those in the surveillance group were more likely to be diagnosed at an early stage and have smaller tumours — 39% had stage one cancer, compared with just 10% in the control group. At the earliest stages, pancreatic cancer can be surgically removed, improving outcomes. The five-year-survival rate was also much higher for the group that underwent yearly surveillance (50% compared with 9% for the control group).
Screening for pancreatic cancer, however, is tricky. Beyond the vague nature of early symptoms, the disease itself is much rarer than many other cancers — the lifetime risk is between 1% and 2%, so screening everyone isn’t feasible. “You can have universal screening for breast cancer and colon cancer,” says Michael Goggins, a gastroenterologist at Johns Hopkins University in Baltimore, Maryland. For pancreatic cancer, however, “the numbers don’t add up”, he says. Routine imaging is recommended for some people with an elevated risk, including those with a family history of the disease, with certain genetic variants that make them more susceptible or with some types of pancreatic cyst. But those individuals account for only about 10–15% of pancreatic cancer cases. To catch the other 85% early, researchers first need to find a way to identify more people with a high enough risk of the disease that they would benefit from screening. But even for people with risk factors, identifying the disease is like finding a needle in a haystack. The aim is to bring it down to “a very small haystack before you start looking”, says Suresh Chari, a gastroenterologist at MD Anderson Cancer Center in Houston, Texas.
At the same time, researchers need easier ways of detecting pancreatic cancer. The gold-standard imaging tools physicians currently use to spot the disease — MRI and endoscopic ultrasound — are costly and not widely available. So, they are working to identify signatures in the blood called biomarkers that can signal the presence of early-stage cancer.
It’s a daunting problem, and an urgent one. Models suggest that by 2030, pancreatic cancer will become the second leading cause of cancer deaths in the United States, surpassing colorectal cancer, and the third leading cause of cancer deaths in Europe. “We’re trying to give more patients the opportunity for cure,” says Randall Brand, a gastroenterologist at the University of Pittsburgh, Pennsylvania.
Shrinking the haystack
Risk factors for pancreatic cancer include old age, obesity, smoking, alcohol and diabetes. But even for people at risk, the disease is rare. People with type 2 diabetes, for example, have about a twofold increased risk, but this still doesn’t amount to many people — certainly not enough to screen the tens of millions of people living with diabetes in the United States. “From an early-detection standpoint, it wasn’t very helpful,” Chari says.
In the 2000s, Chari sifted through the literature and came across something he hadn’t seen before: in some cases, diabetes might be not just a risk factor, but also a symptom of pancreatic cancer. Chari wondered whether he would find more pancreatic tumours in people who were newly diagnosed than in those who had lived with the disease for years.
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