Cancer of the pancreas: The deadliest cancer

Pancreatic cancer has been in the public eye lately because it has afflicted several well-known people  the most prominent being the iconic Apple founder Steve Jobs who died two weeks ago. The list also includes US Supreme Court Justice Ruth Bader Ginsburg, actor Patrick Swayze, and Randy Pausch, computer science professor at Carnegie Mellon University whose inspirational last lecture became a YouTube sensation and, as a book, a national best seller. Here in the Philippines, we followed the fight for survival of popular movie actor Rudy Fernandez who lost his battle against this deadly disease a few years ago.

It’s odd that this disease would strike so many famous people because in fact, pancreatic cancer is fairly uncommon. Only about 43,000 cases are diagnosed in the United States each year, putting it far behind prostatic cancer (218,000 a year), breast cancer (209,000 a year), and colorectal cancer (143,000 a year)  yet because pancreatic cancer is so hard to treat, it has a much higher mortality rate than any of these more common malignancies.

In the Philippines, it ranks only as the 14th leading cause of cancer (an estimated 1,873 new cases in 2005), but it is the 10th leading cause of cancer deaths (1,835 cases in 2005). It is indeed a dreadful disease, and its poor prognosis explains why it gets so much publicity.

The media attention isn’t hard to understand, though. Its morbid interest: No other common cancer has such a poor prognosis. Only about five percent of those diagnosed with pancreatic cancer are alive five years later in contrast to about 66 percent of colon cancer patients and 90 percent of female breast cancer patients.

For a variety of reasons  effective screening, earlier diagnosis, and better treatment  cancer isn’t the proverbial death sentence that it once was. For many today, it is a survivable (if harrowing) condition that can be lived with for many years in relative good health. Pancreatic cancer stands out as a grim exception to this rule.

One organ, two functions

A healthy pancreas is spongy in texture, yellowish-tan in color, and about seven inches in length. It has a creative shape: with a large head that nestles into a loop of the first part of the small intestine (duodenum), a longish body that squeezes behind the stomach, and a narrower tail that reaches the spleen.

Physiologically, the pancreas has two functions. It contains exocrine tissue that produces digestive enzymes, which are transported via ducts to the small intestine, and endocrine tissue that produces hormones, including insulin and glucagon. Over 90 percent of pancreatic cancers come from the exocrine part, and most of them are ductal adenocarcinomas  cancers that form in the lining of the organ’s elaborate ductwork.

Screening for Pancreatic cancer

At least for the time being, rather than seeking universal screening test, researchers have been focusing their efforts on finding one that would work in high-risk populations, which include people who have chronic pancreatitis, a family history of that condition or pancreatic cancer, or mutations in the BRCA2 gene. BRCA2 mutations were first associated with breast cancer and ovarian cancer, but it’s become apparent that they’re also associated with pancreatic cancer.

A group of investigators called the Cancer of the Pancreas Screening Consortium has conducted several small studies of screening tests. One possibility is direct examination of the pancreas with an endoscopic ultrasound, which involves snaking a thin flexible tube  the endoscope  through the patient’s mouth and down the digestive tract. A tiny ultrasound transducer on the tip uses sound waves to create images of the pancreas and nearby structures. Researchers have also tested endoscopic ultrasound in combination with CT scans and, more recently, with a CT scan and a fancy MRI that produces images of blood vessels in the abdomen. Up to now, none of these approaches has produced especially promising results.

Other research groups are looking for pancreatic cancer genes that could be identified in a blood sample. The US National Cancer Institute is backing an effort to find subtle genetic “fingerprints” (single nucleotide polymorphisms, or SNPs) that might be predictive for pancreatic cancer. But the bottom line is that we don’t have a screening test  yet. There’s a lot of promising research going on. I am hopeful that we’ll have a reliable one, at least for the high-risk group, in the not-too-distant future.

Prevention

If early detection is still in the future, how about prevention? Conventional wisdom holds that cancer of the pancreas is not preventable, but a 2009 study may change that view. In 1995 and 1996, 450,416 individuals between the ages of 50 and 71 volunteered for the National Institutes of Health (NIH)–AARP Diet and Health Study. At the start of the study, each participant submitted detailed diet and lifestyle information. Researchers tracked the volunteers through 2003 to see if lifestyle factors influenced the risk of pancreatic cancer.

A total of 1,057 patients were newly diagnosed with the disease during the study. Scientists compared these patients with their healthier peers with regard to five factors: not smoking, limited alcohol use, regular exercise, normal body mass index, and adherence to a Mediterranean-style dietary pattern. People who scored well in all five areas were 58 percent less likely to develop pancreatic cancer than people who scored poorly in all categories.

It’s only one study, but it reinforces earlier research that identified smoking and obesity as pancreatic cancer risk factors. And a series of reports published in 2010 linked a high-carb intake (sugary sodas, fructose, and overall carbohydrate load) to an increased risk of pancreatic cancer.

Course of the disease

Some pancreatic cancers are caught early, discovered incidentally on CT scans and other imaging studies ordered for unrelated reasons. But for the most part, pancreatic cancer is diagnosed after someone has symptoms, which typically include abdominal pain, weight loss (common with cancer but especially so with pancreatic cancer, which may explain the gaunt look of Steve Jobs), and jaundice, a yellowing of the skin from a buildup of bilirubin in the blood, which can occur when a pancreatic tumor impinges on the common bile duct. A major reason pancreatic cancer is so lethal is that the cancer grows and spreads long before it causes any symptoms.

At the time of diagnosis, about 40 percent of pancreatic cancer patients have cancer that has already spread (metastasized) extensively outside the organ. Surgery isn’t an option once that has happened. Another 40 percent of patients have “locally advanced disease”: The cancer hasn’t metastasized, but it may have adhered to or invaded adjacent structures. The pancreas wraps around two large vessels, the superior mesenteric vein and artery. If the cancer gets intertwined with the blood vessels, that may preclude surgery.

Locally advanced pancreatic cancer can be treated with radiation and chemotherapy, but the median survival time is only eight to 12 months. It’s even shorter for people whose cancers have spread.

Surgery

That leaves about 20 percent of pancreatic cancer patients with tumors that are, in the words of cancer specialists, “resectable”  that is, they can be treated surgically. Most of these tumors are confined to the head of the pancreas or its extension, the uncinate process, and the Whipple procedure is the preferred operation (see illustration on Page D-1). By the time the cancer is in the body or tail of the pancreas, it is usually too late to operate, although that’s not always the case. Many doctors have speculated that Steve Jobs underwent a Whipple’s procedure in 2004 aside from his liver transplant.

The post-Whipple prognosis is brightest for patients whose cancers have not spread to nearby lymph nodes. For these “node-negative” patients, the five-year survival rate is 25 to 30 percent. For node-positive patients, it’s only about 10 percent. Regardless of their lymph node status, most Whipple patients will get radiation therapy, chemotherapy, or both, to improve their odds.

But another sobering way to view those survival percentages is to consider the larger percentage of Whipple patients who don’t make it to the five-year mark. Randy Pausch is an example. He was diagnosed in 2006, had a Whipple and follow-up radiation and chemotherapy. Pausch was 47 when he died in 2008, only two years after his surgery. Steve Jobs, at least, lived for seven years, and died at age 56. Meanwhile, for scientists, the long uphill battle against pancreatic cancer continues.

* * *

Dr. Tyrone Reyes’ article on the latest advances in breast cancer management will come out next Tuesday.