Why Is Pancreatic Cancer So Deadly?

Why Is Pancreatic Cancer So Deadly?

After five years, the survival rate is just 7 percent.

Pancreatic cancers, which arise in the pear-shaped gland behind the stomach, are rarely detected early, difficult to treat and often come back. Some 55,000 men and women in the United States will be newly diagnosed with pancreatic cancer this year, according to the American Cancer Society, while 44,300 will die from the disease.

But, incremental advances have begun to emerge, from powerful combinations of cancer drugs to better surgical techniques, while immunotherapies that use our own immune systems to fight against this disease may hold promise for better treatments in the future.

How pancreatic cancer begins
The pancreas produces not only the digestive juices that help break down food—it also produces hormones, such as insulin and glucagon, which are important in controlling blood sugar levels. The vast majority of pancreatic cancers begin in the cells involved in the digestive process.

Overall, these cancers rank as the 10th most common cancer in the United States, but they’re considered the 3rd most deadly behind lung, colorectal and breast cancers. What's more, for most pancreatic cancer patients, overall survival remains poor, an estimated 20 percent at one year and 7 percent for all stages of the disease after five years.

“We’ve not had the same breakthroughs yet that we’ve seen in treating other cancers,” says medical director of surgical oncology Jill Onesti, MD, at Mercy Health in Grand Rapids, Michigan. Immunotherapies, especially, have brought progress in treating some cancers, such as lung cancers and melanoma, she says, but have not worked well in pancreatic cancers. They include targeted drugs, which attack specific proteins or cancer cells that enable them to thrive, as well as vaccines designed to make cancer cells more ‘visible’ to attack by the immune system.

General risk factors
As with all cancers, the risk for developing pancreatic cancer rises with age, as doctors diagnose the most cases in individuals 71 and over. Other risk factors, however, are less well-defined, with hereditary factors—or genes passed on from one family member to another—accounting for no more than 10 percent of cases. Additional general risk factors include:

  • Smoking
  • Chronic pancreatitis or inflammation of the pancreas
  • Obesity
  • Diabetes
  • Being male

Having one of these risk factors does not necessarily mean an individual will get the disease. Diabetic patients, for example, carry a higher risk of developing pancreatic cancer than those without diabetes, but a majority will never get pancreatic cancer, says Dr. Onesti. That said, one recent study suggests diabetes can be an early warning sign in some patients, requiring further study to better define which patients are at the highest risk.

Is early detection possible?
Symptoms of pancreatic cancers tend to be vague, mimicking those of other illnesses. Except for jaundice or pain the upper part of the stomach, Onesti says, symptoms can be difficult to interpret, with many of these cancers found during CT scans for other health issues.

Not surprisingly, the ultimate research goal is early detection, when chances for successful treatments are best. Liquid biopsies—blood tests that scour the blood for the genetic trail tumors leave behind as they grow—may offer that capability. “They are not as feasible or as accurate as we need,” Onesti says, referring to these experimental blood tests. “But that’s the hope for the future.”

Advancements in research and treatment
One area where treatment progress has been made, so far, Onesti suggests, has been in surgery for the small number of early-stage patients whose tumors have not spread beyond the pancreas. For this ‘elite’ group, about 10 to 15 percent of patients, she says, “We are doing much better, minimizing the risk and maximizing recovery.” Once hospitalized for upwards of two weeks, many patients today now go home within four or five days, she says.

Advances have also been reported for this same group of patients with traditional chemotherapy. At the June 2018 meeting of the American Society of Clinical Oncology in Chicago, French researchers reported ‘unexpectedly good results’ in survival for patients receiving a four-drug combination (FOLFIRINOX) after surgery, compared with those on a single standard cancer drug. So encouraging were the results, in fact, several investigators predicted the finding could be ‘practice-changing’ in the near future.

And, clinical trials now under way hold promise for further improvement, researchers believe. Some trials involve targeting the stroma, the supportive tissues surrounding pancreatic tumors that are thought to undermine how well chemotherapy works. Others involve checkpoint inhibitors, a new class of drugs whose early successes in treating melanoma and lung cancers hint at possible benefit, eventually, in pancreatic cancer as well. Checkpoint inhibitors block tumors’ ability to escape attack by their use of ‘checkpoint’ molecules in the immune system, which ordinarily enable them to metastasize, or spread.

Experimental vaccines for pancreatic cancer represent another avenue of active research. Unlike traditional vaccines, cancer vaccines are designed to help treat, not prevent disease, Investigators have begun using them in combination with other immunotherapies, including checkpoint inhibitors, in an attempt to improve patient outcomes.

Ultimately, no matter which of these multi-pronged strategies emerge as best, the hope remains the same: to enable patients with these difficult cancers to survive longer and with a better quality of life.

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