Searching for Clinical and Economic Value in Pancreatic Cancer
Published Online: May 07, 2013
Marj P. Zimmerman, MS, BS Pharm; and Stanton R. Mehr
Pancreatic cancer is an extremely aggressive tumor type that continues to carry a dismal prognosis. Research regarding the cause of the cancer has continued, but important breakthroughs have been slow in coming. Additionally, pancreatic tumors demonstrate a resistance to chemotherapy, which has contributed to clinicians’ frustration in obtaining remission, or even a firm foothold in managing it. This may also be related to the relatively late stage of the tumor at thetime of diagnosis. Therefore, early diagnosis and the future discovery of an effective screening method could change the clinical picture and alter the search for value in managing this deadly cancer.
Mortality Increasing Unlike for Other Cancers
Death rates for most cancers have trended downward over the past 10 years; however, this has not been the case for pancreatic cancer. The incidence rate has increased by 0.9% per year in Caucasian men and women and African American men, while remaining stable in all others.1 The Table illustrates the likelihood of developing pancreatic cancer over one’s lifetime.1 The majority of patients (74%) diagnosed will die within 1 year of diagnosis, whereas only 6% will survive for 5 years—this is the lowest relative survival of any cancer tracked by the American Cancer Society and the National Cancer Institute. Patients’ average life expectancy after diagnosis of metastatic disease is only 5 to 7 months.2 It is not one of the top 5 cancers in men or women in terms of incidence, yet it is the fourth leading cause of cancer death among men and women. More than 45,000 Americans will be diagnosed with pancreatic cancer in 2013, and over 38,000 will die this year.1
The incidence of pancreatic cancer increases with age, with the median age at diagnosis being 71 years. More men than women are diagnosed with the disease.1
Pancreatic cancer typically refers to a ductal adenocarcinoma (exocrine pancreatic cancer). A less common type is a neuroendocrine tumor (endocrine pancreatic cancer). The public profile of pancreatic cancer has been raised in recent years with the chronicled cases of Patrick Swayze (who had exocrine pancreatic cancer) and Steve Jobs (who had endocrine pancreatic cancer).3 In fact, the dire prognosis for patients with pancreatic cancer has driven people like Jobs to seek unorthodox treatment and unproven therapies.
Patients with pancreatic neuroendocrine tumors have a somewhat better median overall survival than those with ductal adenocarcinomas. Unfortunately, the incidence of these tumors appears to be increasing.4
The cause(s) of pancreatic cancer are unknown. Family history is a positive risk factor and is identified in 5% to 10% of those diagnosed; the risk increases as the number of family members diagnosed with the disease increases. Smoking is also a risk factor, with a 2.5% to 3.6% increase in risk compared with non-smokers. As the number of life-years of smoking increases, so does the risk for pancreatic cancer.5 Other potential risk factors include age; obesity; alcohol use; consumption of red and processed meat, and fructose sweeteners; chronic pancreatitis; diabetes; chronic infections (eg, hepatitis B virus, hepatitis C virus, and Helicobacter pylori); some surgeries (eg, partial gastrectomy, cholecystectomy); cystic fibrosis; and periodontal disease.1
Pancreatic cancer is usually not detected or diagnosed in the early stages of the disease, as there are no specific symptoms. Symptoms that bring patients to the physician’s office include: nausea, vomiting, abdominal discomfort, abdominal pain that is localized to the tumor area, anorexia, weight loss, generalized weakness, and fatigue. The majority of the tumors develop in the head of the pancreas, which leads to obstructive cholestasis, rather than the tail of the pancreas. Overall, most tumorsare found when only about 15% to 20% of patients are still candidates for surgery.1,5
As would be expected, costs for treating patients who undergo surgery are greater than costs for patients who have nonresectable tumors (either locoregional or metastatic). A Surveillance, Epidemiology, and End Results (SEER) Medicare database study that included patients diagnosed between 2000 and 2007 found the mean total costs for those 3 patient groups to be $134,000 (surgical candidates), $65,300 (patients with locoregional tumors), and $49,000 (patients with metastatic disease), with an average cost of $61,700. The largest portion of the costs was related to hospitalizations and cancer-related procedures (Figure).6 Undoubtedly, improved treatment strategies may increase the cost of treating patients with pancreatic cancer by increasing their lifespans.
Genetics and Biomarkers
Pancreatic cancer is genetically heterogeneous. One study analyzing 24 tumors found 63 genetic abnormalities in each tumor that were believed to be likely relevant for the disease. It has been determined that there are always at least 1 or more genetic defects involving 4 genes in patients with pancreatic cancer.5 Recent research has determined that germline mutations in BRCA1 and BRCA2 predispose women to pancreatic cancer, doubling their risk for developing it. The 5-year survival for these individuals was no greater than 5%.7
Epidermal growth factor receptor (EGFR) overexpression has been identified in 40% to 65% of pancreatic tumors. This overexpression leads to tumors being resistant to chemotherapy and an even poorer prognosis.8 Since pancreatic tumors vary so much between patients, a highly individualized approach to treating the disease will probably be needed to improve patient outcomes.9
Currently, only 1 biomarker is approved by the US Food and Drug Administration for pancreatic cancer, serum Ca-19-9 (carbohydrate antigen 19-9, also known as cancer antigen-GI and CA-GI).10 This marker is useful for identifying the tumor location, stage, and resectability.11 However, not all pancreatic tumors produce Ca-19-9; therefore, it is not sensitive or specific enough to be used as a screening test.1,12 However, the test does have value for evaluating effectiveness of treatment and early detection of recurrent disease.5
Other frequently used tests include endoscopic ultrasound, helical computed tomography, magnetic resonance imaging, and endoscopic retrograde cholangiopancreatolography. To confirm the diagnosis, fine-needle aspiration biopsy is standard procedure.1,13
Staging of Pancreatic Cancer
Staging of the disease guides the type of treatment that will be the most effective. The 4 stages associated with pancreatic cancer are differentiated by the location of the tumor and whether it has spread to lymph nodes and distant organs. Stage I indicates that the tumor is restricted to the pancreas, and stage IV describes cancer that has spread to a distant organ, such as the liver or lungs. Patients with stage III or IV tumors are generally not candidates for surgical resection, and this comprises about 80% of patients.13,14 The lethality of this cancer in late stages cannot be overemphasized; survival is somewhat greater when diagnosed at an earlier stage. When a patient has surgery after being diagnosed with stage I or stage II cancer, the 5-year survival is 20% to 25%, whereas a patient diagnosed with stage IV cancer has a 5-year survival that is below 1%.1,15
Surgery is the only treatment option that can cure early-stage disease. However, a small percentage of patients present with stage I pancreatic cancer, because of the difficulty in diagnosing it. Surgical procedures most commonly performed include cephalic pancreatoduodenectomy (also known as the Whipple procedure), distal pancreatectomy, and total pancreatectomy. Predictors of improved survival include younger age and early-disease stage.5,16 After surgery, adjuvant chemotherapy either alone or in combination with radiation therapy has been shown to improve survival. Neoadjuvant therapy, both chemoradiation or chemotherapy in combination or alone, are also options, especially when the patient has locally advanced or borderline rescectable disease. In patients undergoing surgery, the chemotherapy regimens initiated after the surgery usually include gemcitabine, 5-fluorouracil (5-FU) with leucovorin, or capecitabine.14
Since surgery for pancreatic cancer can involve several organs in the digestive system in addition to an already diseased organ, several potential morbidities should be considered. Up to 80% of patients undergoing surgical procedures for pancreatic cancer will require oral pancreatic enzyme replacement therapy (PERT). The dose of lipase required usually ranges from 160,000 to 400,000 units daily. A proton pump inhibitor may be added to improve the efficacy of the PERT, if there is adequate gastric acid secretion.17 Since at least a portion of the pancreas is removed during surgery, the body’s ability to produce insulin is compromised. As a result, up to 50% of patients develop diabetes and require insulin therapy postsurgery.18 Other complications observed after surgery include gastroparesis, dumping syndrome, and vitamin and mineral deficiencies.19
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