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Why Is Pancreatic Cancer So Deadly?

Why Is Pancreatic Cancer So Deadly?

After five years, the survival rate is just 9 percent.

Pancreatic cancers are rarely detected early, are difficult to treat—and they often come back. An estimated 60,430 men and women in the United States will be newly diagnosed with pancreatic cancer in 2021, according to the American Cancer Society. The organization projects that 48,220 will die from the disease, as well.

But incremental advances have begun to emerge, from powerful combinations of cancer drugs to better surgical techniques. What’s more, 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 is a pear-shaped gland located behind the stomach. It produces digestive juices that help break down food as well as hormones, such as insulin and glucagon, that are important to controlling blood sugar levels. The vast majority of pancreatic cancers begin in the cells involved in the digestive process.

Overall, pancreatic cancer ranks as the 11th most common cancer in the U.S., but causes the 3rd most cancer deaths per year, behind lung and colorectal cancers. What's more, for most pancreatic cancer patients, overall survival remains poor; it’s an estimated 28 percent at one year and 9 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 Jill Onesti, MD, medical director of surgical oncology at Mercy Health in Grand Rapids, Michigan. Immunotherapies, especially, have brought progress in treating some cancers, such as lung cancers and melanoma, but have not worked well in pancreatic cancers, she says. These treatments include targeted drugs, which attack specific proteins on cancer cells that enable them to thrive, as well as vaccines designed to make cancer cells more “visible” to attack by the immune system.

What are the risk factors for pancreatic cancer?
As with all cancers, the risk for developing pancreatic cancer rises with age. Doctors diagnose the most cases in individuals 65 and over. Other risk factors, are less well-defined, with inherited genetic mutations 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 or more of these risk factors does not necessarily mean an individual will get the disease. People with diabetes, 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 in the upper part of the stomach, Onesti says, symptoms can be difficult to interpret. Many of these cancers are found during CT scans for separate health issues.

Not surprisingly, the ultimate goal of research into the disease is early detection, when chances for successful treatments are best. Liquid biopsies—blood tests that scour the blood for the genetic trail that tumors leave behind as they grow—may offer that capability.

“They are not as feasible or as accurate as we need,” Onesti says of these experimental blood tests. “But that’s the hope for the future.”

Advancements in research and treatment
One area where progress in treatment has been made, Onesti says, has been in surgery for the small number of early-stage patients whose tumors have not spread beyond the pancreas. For this “elite” group of about 15 to 20 percent of patients, she says, “we are doing much better, minimizing the risk and maximizing recovery.” Once routinely hospitalized for upwards of two weeks, many patients today can go home within four or five days, she adds.

Clinical trials 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 in pancreatic cancer. 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 vaccines in combination with radiation, chemotherapy and other immunotherapies, including checkpoint inhibitors, in an attempt to improve patient outcomes.

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

Medically reviewed in January 2021.

Sources:

American Cancer Society. “Survival Rates for Pancreatic Cancer.” January 8, 2020. Accessed January 14, 2021.
American Cancer Society. “Key Statistics for Pancreatic Cancer.” January 2021. Accessed January 14, 2021.
National Cancer Institute. “Pancreatic Cancer Treatment (Adult) (PDQ®)–Patient Version.” December 11, 2020. Accessed January 14, 2021.
MedlinePlus. “Pancreatic Cancer.” October 14, 2020. Accessed January 14, 2021.
National Cancer Institute. “Pancreatic Cancer—Patient Version.” 2021. Accessed January 14, 2021.
American Cancer Society Cancer Statistics Center. “2021 Estimates.” 2021. Accessed January 14, 2021.
American Cancer Society Cancer Statistics Center. “Pancreas.” 2021. Accessed January 14, 2021.
Cancer Patients Alliance. “Pancreatic Cancer Prognosis & Survival.” 2021. Accessed January 14, 2021.
American Cancer Society. “Pancreatic Cancer Risk Factors.” June 9, 2020. Accessed January 14, 2021.
ST Chari. “Detecting early pancreatic cancer: problems and prospects.” Seminars in Oncology. August 2007. 34(4), 284–294.
Stony Brook Medicine. “FAQs about Early Detection of Pancreas Cancer.” 2021. Accessed January 14, 2021.
Science Daily. “DNA and protein 'liquid biopsy' for early pancreatic cancer better than either alone.” September 4, 2017.
Roche. “What is liquid biopsy?” 2021. Accessed January 14, 2021.
American Cancer Society. “What’s New in Pancreatic Cancer Research?” February 11, 2019.
National Cancer Institute SEER. “Pancreas/Survival Rate.” 2021. Accessed January 14, 2021.
Cancer.net. “Pancreatic Cancer: Risk Factors.” May 20201. Accessed January 14, 2021.
National Cancer Institute. “The Genetics of Cancer.” October 12, 2017. Accessed January 14, 2021.
N Kamyabi, V Bernard, A Maitra. “Liquid biopsies in pancreatic cancer.” Expert Review of Anticancer Therapy. 2019 Oct;19(10):869-878.
UpToDate.com. “Initial chemotherapy and radiation for nonmetastatic, locally advanced, unresectable and borderline resectable, exocrine pancreatic cancer.” December 2020. Accessed January 14, 2021.
AN Hosein, RA Brekken, A Maitra. “Pancreatic cancer stroma: an update on therapeutic targeting strategies.” Nature Reviews: Gastroenterology & Hepatology. May 11, 2020. 17, pages487–505(2020).
A Henriksen, A Dyhl-Polk, et al. “Checkpoint inhibitors in pancreatic cancer.” Cancer Treatment Reviews. August 2019;78:17-30.
National Cancer Institute. “Clinical Trials Using GVAX Pancreatic Cancer Vaccine.” 2021. Accessed January 14, 2021.

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