Early detection and prevention of pancreatic cancer:Is it really possible today?

Pancreatic cancer is the 4th leading cause of cancerrelated death in Western countries.Considering the low incidence of pancreatic cancer,population-based screening is not feasible.However,the existence of a group of individuals with an increased risk to develop pancreatic cancer has been well established.In particular,individuals suffering from a somatic or genetic condition associated with an increased relative risk of more than 5-to 10-fold seem to be suitable for enrollment in a surveillance program for prevention or early detection of pancreatic cancer.The aim of such a program is to reduce pancreatic cancer mortality through early or preemptive surgery.Considering the risk associated with pancreatic surgery,the concept of preemptive surgery cannot consist of a prophylactic removal of the pancreas in high-risk healthy individuals,but must instead aim at treating precancerous lesions such as intraductal papillary mucinous neoplasms or pancreatic intraepithelial neoplasms,or early cancer.Currently,results from clinical trials do not convincingly demonstrate the efficacy of this approach in terms of identification of precancerous lesions,nor do they define the outcome of the surgical treatment of these lesions.For this reason,surveillance programs for individuals at risk of pancreatic cancer are thus far generally limited to the setting of a clinical trial.However,the acquisition of a deeper understanding of this complex area,together with the increasing request for screening and treatment by individuals at risk,will usher pancreatologists into a new era of preemptive pancreatic surgery.Along with the growing demand to treat individuals with precancerous lesions,the need for low-risk investigation,lowmorbidity operation and a minimally invasive approach becomes increasingly pressing.All of these considerations are reasons for preemptive pancreatic surgery programs to be undertaken in specialized centers only.

Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals

Pancreatic ductal adenocarcinoma(PDAC) is a lethal neoplasia, for which secondary prevention(i.e., screening) is advisable for high-risk individuals with "familiar pancreatic cancer" and with other specific genetic syndromes(Peutz-Jeghers, p16, BRCA2, PALB and mismatch repair gene mutation carriers). There is limited evidence regarding the accuracy of screening tests, their acceptability, costs and availability, and agreement on whom to treat. Successful target of screening are small resectable PDAC, intraductal papillary mucinous neoplasms with high-grade dysplasia and advanced pancreatic intraepithelial neoplasia. Both magnetic resonance imaging(MRI) and endoscopic ultrasound(EUS) are employed for screening, and the overall yield for pre-malignant or malignant pancreatic lesions is of about 20% with EUS and 14% with MRI/magnetic resonance colangiopancreatography. EUS performs better for solid and MRI for cystic lesions. However, only 2% of these detected lesions can be considered a successful target, and there are insufficient data demonstrating that resection of benign or low grade lesions improves survival. Many patients in the published studies therefore seemed to have received an overtreatment by undergoing surgery. It is crucial to better stratify the risk of malignancy individually, and to better define optimal screening intervals and methods either with computerized tools or molecular biomarkers, possibly in large multicentre studies. At the moment, screening should be carefully performed within research protocols at experienced centres, offering involved individuals medical and psychological advice.