Pancreatic Cancer in Hereditary Pancreatitis: Consensus Guidelines for Prevention, Screening and Treatment

Pancreas adenocarcinoma is now the 10th-leading cause of cancer in the United States but the fourth leading cause of cancer-related death. By 2030, it is expected to be the second-leading cause of cancer-related death in the United States after lung cancer. Understanding the genetics, molecular biology, and immunology of pancreas cancer has been key to making inroads in developing new therapies. This chapter highlights recent progress.

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of only 8% and is estimated to be the second leading cause of cancer-related deaths by 2021. Prior convention held that screening for PDAC would not be beneficial; however, a deeper understanding of the carcinogenesis pathway supports a potential window of opportunity among the target population. Screening for PDAC is not a standard practice among the general population because of its low incidence. However, screening may be beneficial for individuals with familial history, chronic diseases with genetic predispositions, or inherited cancer syndromes, such as hereditary breast ovarian cancer syndrome, hereditary pancreatitis, Peutz-Jeghers syndrome, familial atypical multiple mole melanoma, Lynch syndrome (hereditary nonpolyposis colorectal cancer), ataxia telangiectasia, and Li-Fraumeni syndrome, all of which have been associated with an increased risk of developing PDAC. The screening strategies among these high-risk individuals are targeted to identify precursor lesions and PDAC at an early resectable stage. This review describes the risk factors for pancreatic cancer, especially the genetic risk factors in high-risk individuals and current screening strategies available for PDAC.

Pancreatic ductal adenocarcinoma (PDAC), although a rare disease, has a poor prognosis. With 5-year overall survival of 8%, there is a critical need to detect PDAC early or at a premalignant stage. Current screening methods are largely imaging based, but a more focused screening approach based on modifiable and nonmodifiable risk factors may improve the efficacy and likely outcomes of screening. In addition, the pathologic mechanisms that lead to the development of PDAC are discussed in an effort to further understand the targets of pancreatic cancer screening. The focus of this article will be inherited pancreatic cancer syndromes and familial pancreatic cancer, which together compose up to 10% of PDAC. Understanding the methods and targets of PDAC screening in high-risk individuals may translate to improved morbidity and mortality.

Pancreatic adenocarcinoma represents the fourth most common cause of cancer mortality and death due to pancreatic cancer (PC) have increased since 2003. Its incidence has also raised about 30% in the past decade and it is expected to become the second cause of cancer mortality by 2020 in the USA. Most PC present with metastatic disease and improvements in treatment outcomes for this group have been disappointing. These observations support the idea that screening to identify patients at an earlier stage might be an important strategy in improving overall PC outcomes. Many protocols have been tested, nevertheless, by now there is no effective screening program.

Given the overall low incidence of disease and the current lack of accurate, inexpensive and noninvasive screening tests, the consensus is that widespread population-based screening for PC in the general population or in patients with only one affected first-degree relative is neither practicable nor indicated in most countries. However, a different scenario is screening patients with higher risk for PC, most of them with hereditary conditions predisposing the development of this neoplasia. In fact, some guidelines are now available helping to select these individuals at risk and to screen them, in order to achieve early detection of PC.