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Why Can’t We Stop Pancreatic Cancer?

New York Times

Pancreatic cancer, which will be diagnosed in about 56,770 people in the United States this year, is the only cancer with a rising mortality rate through 2014, although five-year survival has begun to inch up, from 8 percent to 9 percent by 2016. It remains the nation’s third leading cause of cancer deaths, after cancers of the lung and colon, and it is on track to overtake colon cancer within a decade. Three-fourths of people who develop pancreatic cancer die within a year of diagnosis, and only about one in 10 live five years or longer.

Perhaps like me you’ve wondered why modern medicine has thus far failed to gain the upper hand against pancreatic cancer despite having achieved major survival advances for more common cancers like breast and colon. What follows is a large part of the answer.

Although pancreatic cancer is a relatively uncommon malignancy, accounting for only 3 percent of life-threatening cancers over all, it is one of medicine’s most challenging. Aside from avoiding smoking, obesity and Type 2 diabetes, there is little a person can do to prevent it, and there is nothing comparable to mammography or colonoscopy to screen for it in seemingly healthy individuals when it is most amenable to cure.

Among the small minority of patients who are cured of this disease, it is nearly always discovered accidentally at a very early symptom-free stage during an unrelated medical procedure. By the time this cancer produces symptoms, it has nearly always spread beyond the pancreas. In fact, surgery is a treatment option in relatively few patients because the cancer is usually already too advanced at diagnosis for surgery to have survival value.

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Last month, the United States Preventive Services Task Force reiterated its assessment of 15 years ago that evidence is lacking for an early-detection screening tool for pancreatic cancer that can improve health and survival chances in the general population. The ability to screen for this disease in people without symptoms and known risk factors got the same dismal “D” rating, discouraging practitioners from attempting it.

Among 100,000 people of average risk, pancreatic cancer develops in only 13. By contrast, more than four in 100 people will develop colon cancer, and one woman in eight who lives to age 80 will develop breast cancer.

Only those with well-established risk factors for pancreatic cancer are currently considered candidates for close surveillance. They include a family history of two or more first-degree relatives with the disease, and the development of diabetes in a person over 50.

Pancreatic cancer has thus far resisted the screening and early detection tools that modern medicine has developed and used successfully to reduce deaths from so many other forms of cancer. Although some progress has been made in understanding the genetics of the disease and identifying possible markers in the blood, this has yet to translate into measures useful in clinical practice.

A large part of the problem with early detection lies with the location and size of this vital organ. The pancreas is a source of enzymes that facilitate digestion and of the hormone insulin that regulates blood sugar, making it available to tissues for energy. It is a mere six inches long sitting deep in the abdomen behind the stomach and surrounded by the spleen, liver and small intestine.

Therefore, you’d be unlikely to feel the presence of a small pancreatic tumor, and any early symptoms that might result from one, such as loss of appetite, are easily attributed to something far less ominous. Nor would you or an examining doctor be able to notice a premalignant lesion, as can happen with cancers of the cervix, colon and skin.

In an editorial entitled “Screening for Pancreatic Cancer – Is There Hope?” in JAMA Internal Medicine in August, Dr. Anne Marie Lennon and coauthors at Johns Hopkins University wrote that there are three well-known precursor lesions to pancreatic cancer: pancreatic intraepithelial neoplasia (PanIN); intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms (MCNs).

“The majority of cancers originate from PanINs, which measure less than 5 millimeters in diameter and can only be seen using a microscope,” the authors noted. Not only can’t PanIN lesions be felt, a CT scan or MRI would not pick them up. The other two precursor lesions are larger but account for only about 15 percent of cancers.

With current technology, the Hopkins team wrote, it is often impossible to distinguish between a precursor lesion that harbors an early cancer or may develop one, and relatively harmless lesions that can be safely watched. This is an important distinction because most lesions are unlikely to progress and the surgery to remove them can be hazardous. Some progress has been made, the team noted, in using tumor markers to determine which precursor lesions are likely to become cancer.

Further complicating early detection is the speed at which pancreatic cancer seems to progress. According to Dr. Lennon and coauthors, recent study findings “suggest that early stage pancreatic cancers often invade the veins, which drain directly to the liver and result in early metastatic spread,” which may explain why only 10 percent of patients have localized disease at diagnosis.

Still, there remains the possibility that one or more blood tests may hold the key to early detection and a future decline in the currently horrific mortality rate. “Novel blood tests can detect a combination of pancreatic cancer DNA and pancreatic cancer-related protein markers,” the team wrote. They noted that “in a multicenter study of 221 patients, results of a multimarker blood test helped identify 64 percent of patients with early pancreatic cancer,” 20 percent of whom did not yet have symptoms of the disease.

Given that early detection can increase the chances of surviving pancreatic cancer by six-fold, the need for noninvasive biomarkers that can detect this cancer in its earliest stage is considered urgent, and organizations like the Kenner Family Research Fund in New York have been encouraging both the pharmaceutical industry and medical groups to develop them.

Meanwhile, it may help extend survival in some people if they recognize symptoms of pancreatic cancer and act on them without delay. Possible symptoms include loss of appetite, abdominal pain that radiates to the back, new-onset diabetes in someone over 50, jaundice, itchy skin, a change in how alcohol tastes, and pale odd-smelling feces that float.

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