The death of Steve Jobs from a form of pancreatic cancer last year, and of Patrick Swayze and Michael Landon before him has brought this form of cancer into the public eye. Although pancreatic cancer is not one of the more common forms of cancer (it’s number 10 in the United States), its mortality rate is disproportionately high. In 2011, for example, an estimated 37,660 patients died of pancreatic cancer, making it the fourth most common cause of cancer death in men and women. The incidence and mortality rates for pancreatic cancer have unfortunately not changed much over the past several decades. The majority of these tumors (85%) are known as adenocarcinomas.
Tobacco use, obesity, and chronic pancreatitis have been associated with increased risk of pancreatic adenocarcinoma. Men and women have essentially equal risk for this form of pancreatic cancer, but African Americans have a higher incidence than white Americans.
One of the reasons that pancreatic cancer has such a high mortality rate is that patients often don’t have symptoms for a long time, and therefore it typically remains undiagnosed until late in the course of the disease.
Approximately 90% of pancreatic adenocarcinoma is sporadic, meaning that there is no family history of the disease. The other 10% of cases do seem to have a genetic link. The genes most commonly associated with familial cases of pancreatic adenocarcinoma are BRCA-1 and BRCA-2 (which are better known as the “breast cancer genes”), and the most commonly lost gene is the p16/CDKN2A gene on chromosome 9p.
One of the reasons that pancreatic cancer has such a high mortality rate is that patients often don’t have symptoms for a long time, and therefore it typically remains undiagnosed until late in the course of the disease. The symptoms that do, finally, occur include jaundice, abdominal pain, weight loss, and sometimes development of diabetes (due to disease of the insulin-secreting cells of the pancreas). Therefore, developing diabetes in adulthood along with weight loss should prompt one’s doctor to investigate pancreatic problems further.
There has been great interest in using blood tests to diagnose pancreatic cancer, although the test currently available (called CA 19-9) is not 100% accurate.
Doctors will typically order a CAT scan (CT) or right upper quadrant (RUQ) ultrasound if the patient has new onset jaundice. Diagnosis also requires tissue biopsy of the pancreatic cells. There has been great interest in using blood tests to diagnose pancreatic cancer, although the test currently available (called CA 19-9) is not 100% accurate. It can come back positive in response to benign conditions like pancreatitis, and, conversely, it can be falsely negative in people who do have pancreatic cancer. Therefore, CA 19-9 is not used to make a diagnosis of pancreatic cancer, but may help doctors learn more, in addition to the other methods mentioned above.
By the time of diagnosis, nearly 80% of patients with pancreatic cancer cannot proceed with surgery.
The most common procedure performed is the Whipple, which involves resection of the part of the pancreas, parts of the duodenum, the common bile duct, and the gallbladder. The distal (lower) portion of the stomach is also removed in the “classic” Whipple. (For those who are interested, this YouTube video provides an explanation of the procedure.) A different surgery is needed for pancreatic cancers in the pancreatic body or tail, which involves distal pancreatectomy, often along with splenectomy.
One study compared people who had a chemotherapeutic medicine called gemcitabine after surgery to those who did not receive it. At the end of about 53 months, 74% of the patients in the gemcitabine group and 92% of the control group had recurrence of their pancreatic cancer. The median length of time during which the patients were disease-free was significantly longer in those receiving gemcitabine (13.4 months vs. 6.9 months), but unfortunately, no overall survival difference was shown.
Unfortunately, most studies don’t show a survival benefit for neoadjuvant therapy compared to adjuvant therapy. Currently, researchers are recruiting for a phase III study that compares adjuvant therapy to a combination of neoadjuvant and adjuvant therapy for operable pancreatic cancer. This trial should help answer the question of the role of neoadjuvant therapy in resectable pancreatic cancer (for more information, visit clinicaltrials.gov).
For cases that are borderline operable, neoadjuvant therapy makes the most sense, as it would potentially push the case into the operable realm. No prospective phase III trials have addressed this scenario, however. The current approach varies by hospital, but it appears that most physicians prefer neoadjuvant therapy as opposed to immediate surgery. Fortunately, there are several ongoing trials that are looking at neoadjuvant chemotherapy in patients with borderline resectable disease to establish the possible benefits of this approach (for example, using folfirinox chemotherapy).
Systemic chemotherapy is used for patients who are not eligible for surgery. It is mostly limited to patients who are in good overall health. Gemcitabine, mentioned earlier, is used as the first line option both for extending one’s lifespan, as well as for relief of symptoms. The combination of gemcitabine with other medications has not been shown to be of any greater benefit than gemcitabine alone. The only combination currently approved by the FDA is gemcitabine with a drug called erlotinib, which showed a very slight improvement in survival from 5.91 months to 6.24 months (compared to gemcitabine alone.)
Until recently, gemcitabine and the less commonly used combination with erlotinib were the only treatments for inoperable pancreatic cancer. Last year, one study found that a drug called folfirinox worked even better than gemcitabine in reducing the spread of the cancer and extending one’s lifespan survival (11.1 months vs. 6.8 months). However, it is more toxic than gemcitabine, with higher risk of neutropenia (low white blood cell count) and diarrhea, among other side effects. Therefore, only patients who are otherwise in good health should be offered this treatment.
Somewhat unique to pancreatic cancer is the need for considerable palliative procedures in the course of illness. Symptoms occurring from biliary obstruction, for example, occur in more than 65% of patients with pancreatic cancer. Cancer-related pain is also a major symptom that sometimes cannot be managed with oral pain medications alone. Therefore, one’s doctor must have a thorough understanding of the options that are currently available to manage these symptoms.
Sometimes a biliary stent cannot be placed, so a biliary drain may be used instead. A biliary bypass may also be used, usually for people who are having surgery but whose cancer is found to be inoperable during the operation.
Some patients may also have gastric (stomach) obstruction. In these cases, a doctor may place a stent to relieve the obstruction. Other options may also be possible depending on the nature of the disease, the overall health of the patient, and his or her life expectancy.
Symptoms of pancreatic insufficiency result in steatorrhea (fat being present in the feces), abdominal cramps, weight loss, and malnutrition. The treatment is based on the symptoms one has, rather than diagnostic testing, given the high prevalence of this problem in patients with pancreatic cancer. Pills containing pancreatic enzymes can be taken orally, with half of the dose taken at the start of the meal and half taken in the middle of the meal, to help the body digest food.
Despite some recent advances, pancreatic cancer continues to be one of the most lethal cancers in the twenty-first century. Surgery provides the only chance at curing the disease but even with surgery, pancreatic cancer is still highly fatal. Additional therapies are typically used to improve the results of surgery alone. When surgery is not an option, systemic chemotherapy with gemcitabine and more recently, folfirinox, is often used. Until more effective therapies are found, managing symptoms such as pain and biliary obstruction are key elements in the management of patients with pancreatic cancer. Getting good palliative care is important to help manage these symptoms as well as to arrange for hospice care in the later stages of the disease. Hopefully, the coming years will bring more treatment options and, perhaps more importantly, better screening methods, so that pancreatic cancer will become a more curable form of cancer.