Pancreatic Cancer on the Rise

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Over 60,000 new cases of pancreatic cancer are anticipated in the U.S. in 2021. The incidence is rising at a rate of 0.5% to 1% per year, and pancreatic cancer is projected to become the second-leading cause of cancer death in the U.S. by 2030. Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of pancreatic tumors. Most patients with pancreatic cancer present with nonspecific symptoms at an advanced stage with disease that is not amenable to curative surgery. No effective screening tests exist. The five-year survival rate approached 10% for the first time in 2020, as compared to 5.26% in 2000. The median age at diagnosis is 71, with the male/female incidence ratio of 1.3/1.0. At presentation, 50% of patients have metastatic disease, while only 10% to 15% have localized disease that is operable.

By far, the largest lifestyle risk factor for PDAC is cigarette smoking. There is a modest association with daily alcohol consumption (three or more drinks per day), and chronic pancreatitis increases the risk of PDAC by 13-fold. Other risk factors include obesity, and a diet high in processed meat, high-fructose corn syrup-containing beverages, and saturated fat. Nearly 10% of patients have pathologic gene variants including BRCA1, BRCA2, and ATM (ataxia telangiectasia syndrome). As mentioned above, presenting symptoms can be mild and vague and include loss of appetite, indigestion, and change in bowel habits. Because most tumors arise in the head of the pancreas (which the common bile duct passes through), some patients present with symptoms of biliary obstruction which include dark urine, jaundice, appetite loss, fatigue, weight loss, and pancreatic insufficiency. Because the pancreas makes insulin, new-onset diabetes or worsening of pre-existing diabetes may be a primary manifestation of PDAC.

Diagnosing PDAC involves the use of imaging studies like CT and MRI scans. There is no specific blood test for it, however serum carbohydrate antigen 19-9 (CA 19-9) is a well-established biomarker for PDAC. Endoscopic ultrasound-guided fine needle aspiration is used for biopsy. Endoscopic retrograde cholangiopancreatography (ERCP) can be useful to open and place a stent in a blocked common bile duct. Staging the tumor is an important factor in determining prognosis, and PDAC often spreads to the liver, lymph nodes, lungs, peritoneum, and bones. Non-surgical treatments usually involve traditional chemotherapies, most commonly FOLFIRINOX (fluorouracil, oxaliplatin, irinotecan, and leucovorin) in high-functioning patients. The role of stereotactic radiotherapy is still being investigated. Novel therapies are being evaluated to treat those with genetic mutations other than BRCA.

As further research is conducted, the search for a reliable and specific test or biomarker for PDAC goes on. As mentioned above, CA 19-9 is a useful biomarker, but it is non-specific. The key is finding a way to diagnose pancreatic cancer early in the disease course when it is still both treatable and curable, instead of finding it way too late as unfortunately happens all too often today.

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By Peter Galvin, MD

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