Pancreatic Cancer: Early Detection and Surveillance

Pancreatic cancer (PC) is characterized by extremely high mortality and poor prognosis. Unfortunately, compared with other malignancies, there has been little improvement in the survival rate of patients with PC in recent decades. In almost all cases, pancreatic cancer is detected in the non-resectable advanced stages because the disease is usually asymptomatic in the early stages. At the time of diagnosis 20% of patients have localized disease, approximately 30% present with regional disease, and more than 50% present with distant disease. The only cure pancreaticoduodenectomy, is available to fewer than 20% of patients. Moreover, chemotherapy and immunotherapy regimens have limited efficacy in patient with nonresectable disease [1]. Since therapeutic choices are limited at the advanced stage, screening and early diagnostic tools are indispensable for a better prognosis. This article reviews current screening methods used in high risk patients and discusses some of the methods in development to improve early detection. keywords: Pancreatic Cancer; Screening; Endoscopic Ultrasound; Biomarkers; Magnetic Resonance Imaging High Risk Population Although most cases of pancreatic adenocarcinomas are thought to be sporadic, up to 10% may be due to an underlying genetic predisposition. “Familial pancreatic cancer” (FPC) has been used to describe families with at least 2 first-degree relatives (FDR) with pancreatic cancer without a known genetic defect. Aggregation of pancreatic cancer in these families is due to an unidentified, autosomal dominantly inherited gene with reduced penetrance. A population-based, case control study conducted in the United States found that individuals with a first-degree relative (FDR) with pancreatic cancer had a 3.2-fold increased risk of developing pancreatic cancer [2] as compared to population controls. Hemminki et al. [3] also demonstrated 1.7-fold increased risk of pancreatic adenocarcinoma in an individual with a parent with pancreatic cancer [3]. The risk of pancreatic cancer based upon family history can be determined using a Mendelian risk assessment tool which calculates the probability that an individual carries a deleterious mutation in a pancreatic susceptibility gene. Current Screening Methods Appropriate combination of biomarkers and imaging technologies greatly improves the accuracy of early diagnosis. Current Biomarkers Cancer Antigen 19-9 This cancer antigen 19-9 (CA 19-9), a sialylated Lewis blood group antigen has been the standard serum tumor marker utilized for diagnosis, prognosis, and recurrence detection in patients with pancreatic cancer. However only 65% of patients with resectable PC have elevated serum CA19-9 levels [and elevated level of CA19-9 has been observed in other gastrointestinal malignancies, such as gastric cancer and colorectal cancer, and in various benign conditions, including chronic pancreatitis and acute cholangitis Therefore, recent efforts have been focused on improving the diagnostic efficacy of CA19-9 by combining it with a panel of markers[4]. Carcinoembryonic Antigen Carcinoembryonic antigen (CEA) CEA is the second most common serum biomarker used in clinical practice for pancreatic cancer diagnosis. It has sensitivity of 54% and a specificity of 79% for discriminating between malignant and benign conditions [5]. However, CEA is less accurate than CA 19-9 for malignant pancreatic cancer diagnosis. Serum Glucose Recently, new-onset diabetes has been recognized as an early manifestation of pancreatic cancer, which could aid the diagnosis of asymptomatic patients with pancreatic cancer. Identification of new-onset diabetes could lead to diagnosis at an early resectable stage, as early as 18 to 24 months [6]. However, several studies have shown either no association or mild increased risk for pancreatic cancer in patients with long-standing diabetes. In one