A rise in the disease in younger people was not followed by an increase in deaths, a study found, and might be a sign of overdiagnosis.
One of the first warnings came in a paper published in 2021. There was an unexpected rise in pancreatic cancer among young people in the United States from 2000 to 2018. The illness can be untreatable by the time it is discovered, a death sentence.
With publication of that report, by Dr. Srinivas Gaddam, a gastroenterologist at Cedars-Sinai Medical Center, researchers began searching for reasons. Could the increase be caused by obesity? Ultraprocessed foods? Was it toxins in the environment?
Alternatively, a new study published on Monday in The Annals of Internal Medicine suggests, the whole alarm could be misguided.
The authors of the paper, led by Dr. Vishal R. Patel a surgical resident at Brigham and Women's Hospital in Boston, did not dispute the data showing a rising incidence. They report that from 2001 to 2019 the number of young people -- ages 15 to 39 -- diagnosed with pancreatic cancer soared. The rate of pancreatic surgeries more than doubled in women and men.
The problem is that the expected consequence of such a rise in cancers did not occur. With more pancreatic cancers in young people, there should be more pancreatic cancer deaths. And there were not. Nor were more young people getting diagnosed with later-stage cancers. Instead, the increase was confined to cancers that were in very early stages.
Many cancers will never cause harm if left alone, but with increasingly sensitive tools, doctors are finding more and more of them. Because there usually is no way to know if they are dangerous, doctors tend to treat them aggressively. But they would never have shown up in death statistics if they had not been found.
It's the hallmark of what researchers call overdiagnosis: a rise in incidence without a linked rise in deaths.
The investigators worked out the puzzle by taking a close look at the nature of those pancreatic cancers. It turns out that statistics on pancreatic cancer lump together very different types of tumors that happen to arise in the same organ, the pancreas, a large flat gland buried deep in the abdomen, behind the stomach.
Adenocarcinoma is a type of tumor that can form in the pancreas and usually has no symptoms until it reaches a late stage. Patients realize something is wrong when they suddenly lose weight and become jaundiced. By then it usually is too late.
Adenocarcinomas are sometimes found earlier because they can show up on abdominal scans done for other reasons. But their incidence at every stage has remained stable in young people. There is no epidemic of adenocarcinomas.
Instead, the sudden rise in pancreatic cancer incidence is largely being driven by another type of tumor -- endocrine cancers. They tend to be indolent, taking years or even decades to grow and spread, but occasionally they can turn malignant.
The study investigators suspect endocrine tumors are being detected by CT or M.R.I. scans, which have gotten increasingly sensitive and are used more and more often. Even if they are not directed at the pancreas they can find lesions on that organ.
"The more you are imaged, the more these things will turn up," said Dr. H. Gilbert Welch, a study author and senior researcher in the Center for Surgery and Public Health at Brigham and Women's Hospital.
"Sometimes we see things on imaging and we have to go after it," said Dr. Folasade May, a gastroenterologist at the University of California, Los Angeles, who was not involved with the study. "People might end up with a big surgery. But it is hard to tell who needs the surgery and who doesn't."
Although guidelines say patients with small endocrine tumors should be monitored with scans, some doctors say it is better to remove those cancers in young patients. The argument is that as years go by, the cancers will have time to grow and become deadly.
The doubling of surgical interventions in young people with pancreatic cancer indicates that many are having that operation.
"A lot of patients say, 'Get it out,'" said Dr. Adewole S. Adamson, an author of the new paper and an overdiagnosis expert at the University of Texas at Austin. "When someone tells you that you have cancer you feel like you have to do something."
But, said Dr. William Jarnagin, a pancreatic cancer specialist at Memorial Sloan Kettering Cancer Center, removing early stage endocrine tumors "has never been proven to be a good strategy."
It might help if endocrine tumors were not labeled as pancreatic cancers, said Dr. Arjun Gupta, a pancreatic cancer specialist at the University of Minnesota who was not involved with the study.
Dr. Gaddam, who raised the alarm on pancreatic cancer incidence a few years ago, praised the new paper and said it was "much needed." As a gastroenterologist, he said, he tries to explain the situation to patients with endocrine cancers.
"I say, 'I know you are going to hate this word -- pancreatic cancer -- but there are two very different types,'" he said. "'This is really great news for what could have been.'"
Then, he added, "I refer them to an oncologist."