Pancreatic Cancer Screening in a Prospective Cohort of High-Risk Patients: A Comprehensive Strategy of Imaging and Genetics

Abstract

Purpose: Pancreatic cancer is a virtually uniformly fatal disease. We aimed to determine if screening to identify curable neoplasms is effective when offered to patients at high risk.Experimental Design: Patients at high risk of pancreatic cancer were prospectively enrolled into a screening program. Endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), and genetic testing were offered by a multidisciplinary team according to each patient's risk.Results: Fifty-one patients in 43 families were enrolled, with mean age of 52 years, 35% of whom were male. Of these patients, 31 underwent EUS and 33 MRI. EUS revealed two patients with pancreatic cancer (one resectable, one metastatic), five with intraductal papillary mucinous neoplasms (IPMN), seven with cysts, and six with parenchymal changes. Five had pancreatic surgery (one total pancreatectomy for pancreatic cancer, three distal and one central pancreatectomy for pancreatic intraepithelial neoplasia 2 and IPMN). A total of 24 (47%) had genetic testing (19 for BRCA1/2 mutations, 4 for CDKN2A, 1 for MLH1/ MSH2) and 7 were positive for BRCA1/2 mutations. Four extrapancreatic neoplasms were found: two ovarian cancers on prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy, one carcinoid, and one papillary thyroid carcinoma. Overall, 6 (12%) of the 51 patients had neoplastic lesions in the pancreas and 9 (18%) had neoplasms in any location. All were on the initial round of screening. All patients remain alive and without complications of screening.Conclusions: Pancreatic cancer screening for high-risk patients with a comprehensive strategy of imaging and genetics is effective and identifies curable neoplasms that can be resected. Ongoing study will better define who will benefit from screening and what screening strategy will be the most effective. Clin Cancer Res; 16(20); 5028-37. ©2010 AACR.Pancreatic adenocarcinoma is the fourth leading cause of cancer death in most western countries (1). In 2009, there were approximately 42,470 new cases of pancreatic cancer diagnosed in the United States, and 35,240 cancer-related deaths (2). Due to the rapid progression and almost uniform fatality of the disease, early detection through screening will be essential to improve outcomes. As premalignant stages of disease, including pancreatic intraepithelial neoplasia (PanIN; refs. 3, 4) and intraductal papillary mucinous neoplasms (IPMN; refs. 5-7), have been identified, and the sensitivity of pancreatic imaging has improved with endoscopic ultrasound (EUS) and high-resolution magnetic resonance imaging (MRI), early detection of small curable pancreatic cancers and premalignant lesions now seems possible. It has been shown that early-stage pancreatic cancer may be resected for cure, as evidenced by a series from Japan where 100% of patients were cured when the pancreatic cancer was <1 cm (8). Unfortunately, no current screening strategy is adequately safe, sensitive, and cost effective to be implemented in the general population, even in tho...

Hereditary Pancreatic Cancer

“…In these asymptomatic individuals, pancreatic cancer was detected in two of them-one resectable and one stage IV pancreatic cancer. Four patients has intraductal mucinous neoplasms (IPMN) lesions, two individuals were diagnosed with ovarian cancer, one individual with retroperitoneal carcinoid, and one with papillary carcinoma of the thyroid [4]. All told, 18% of the 51 asymptomatic individuals in the program were found to have a preneoplastic or neoplastic lesion.…”

“…Estimates vary in the literature, but it is recognized that approximately 3-16% of cases of pancreatic cancer have a hereditary component [3,4,8,9]. What constitutes the definition of hereditary pancreatic cancer also varies between known germline mutations with associations with pancreatic cancer to a family history of pancreatic cancer.…”

“…Thus, due to most pancreatic cancers presenting at a later stage with poor overall survival, early detection methods must be implemented to improve treatment outcomes. Pancreatic cancer has been shown through several studies to have a hereditary disposition with estimates ranging from 3 to 16% of newly diagnosed cases [3,4]. There are several germline mutations that have shown to be at risk for the development of pancreatic cancer, including BRCA1, BRCA2, ATM, PALB2, CDKN2A, STK11, PRSS1, MEN1, MSH2, VHL, TP53, PALLD, EPCAM, MLH1, MSH6, APC, and FANCC [5,6].…”

Pancreatic Cancer Screening: Attempts and Possibilities

“…(EUS) and magnetic resonance imaging (MRI) which are both expensive and invasive and therefore not appropriate for lower risk populations [9,10].…”

Pancreatic Cancer Surveillance: Learning As We Go

“…Mouse models have been created that faithfully recapitulate the human disease for both IMPN-and PanIN-based tumorigenesis and do suggest that with time, these lesions can become lethal ( 3 ). Several centers of surveillance, including the current report by Ludwig and our own center at the University of Washington, have reported fi nding family members with asymptomatic and undiagnosed pancreatic cancer ( 4,5 ).…”