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The Puzzle of Pancreatic Cancer: How Steve Jobs Did Not Beat the Odds—but Nobel Winner Ralph Steinman DidSteve Jobs was a rare case, right down to his death. Announced Wednesday, Jobs's death from "complications of pancreatic cancer" only hints at the vast complexity of the disease to which he succumbed at the age of 56.

Jobs joined recently announced Nobel Prize winner Ralph Steinman, actor Patrick Swayze and football great Gene Upshaw as the latest bold-faced name to die from this aggressive disease—one that even he, with his vast fortune, and Steinman, with his use of experimental immunological treatments, could not forestall indefinitely.

Most pancreatic cancers (53 percent) are diagnosed after they have spread—and those have an exceedingly low survival rate, with just 1.8 percent of patients living for more than five years after diagnosis. (For all types of the cancer, the average five-year survival rate when diagnosed is only slightly higher at 3.3 percent.) So how did Jobs, who was diagnosed in the fall of 2003—and who revealed it publicly in 2004—manage to survive for eight years?

Jobs had a rare form of the cancer, known as neuroendocrine cancer, which grows more slowly and is easier to treat, explains Leonard Saltz, acting chief of the gastrointestinal oncology service at Memorial Sloan-Kettering CancerCenter. "Survival for many years or even decades with endocrine cancer is not surprising." For that type, the sort that Jobs had, "survival is measured in years, as opposed to pancreatic cancer, which is measured in months."  

"When you have a pancreatic neuroendocrine tumor, that is substantially different from pancreatic cancer," Saltz says.

Steinman, on the other hand, did have the type that is usually fatal within a year after diagnosis. "Ralph had the garden variety, poorly differentiated pancreatic cancer," says Sarah Schlesinger, an associate professor of immunology and cell physiology at The Rockefeller University, where she worked with Steinman.

Given the grim prognosis for both these forms of cancer, researchers are hard at work trying to develop better treatments and diagnostics, and to figure out just why one patient might live for eight years—and another for eight months.

Two different kinds
Pancreatic cancer is a rare disease, with about 44,000 new cases diagnosed in the U.S. each year, and a lifetime risk of getting it at about 1.4 percent. The vast majority of those cancers—some 95 percent—are known as adenocarcinomas, the sort that Steinman had. Jobs's form, known as pancreatic neuroendrocrine tumor (pNET), makes up the small fraction of other pancreatic cancer sufferers.

The pancreas itself is essentially two different organs, which means two distinct kinds of tissue—and two very different types of cancer, Saltz points out. The most common kind of pancreatic cancer, the adenocarcinomas, originate in what is known as the exocrine portion of the pancreas. This is the main mass of the organ, which makes digestive enzymes that get shuttled to the gastrointestinal tract via specialized ducts.

"Scattered in that larger organ are thousands of tiny islands," Saltz explains. "These are islands of endocrine tissue," which makes hormones that are secreted into the blood. It was a cancer of these islet cells that Jobs had.

Difficult to diagnose
Pancreatic cancer is so deadly in large part because it is often caught at a very late stage. Unlike lung or colon cancer, it does not create a lot of early symptoms. Saltz said he was hesitant to even list the manifestations (which include upper abdominal pain, weight loss, appetite loss and blood clots) because they are such common complaints that, he noted, everyone would go home and decide by this evening that they had pancreatic cancer.