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Pancreatic cancer (PC) is a relatively uncommon cancer with a disproportionately high mortality rate. The majority of PC cases involve exocrine pancreatic tissue (93%), while the others involve hormone-producing cells (7%).1

In this chapter the discussion of PC will refer to pancreatic ductal adenocarcinoma (PDAC), which is the predominant exocrine pancreatic neoplasm, with particular emphasis on inherited pancreatic cancers. Most PCs are sporadic and account for 90% of the cases.2 The remainder of cases have inherited risk factors, including known genetic susceptibility or familial risk factors.3 We outline the PC epidemiology, their molecular and pathological characteristics, associated risk factors, and management strategies for individuals at risk including screening them for target pathology and treatment based on malignant risk. The implications of PC genetics in the therapy of PC will also be reviewed in this chapter.

Pancreatic Cancer Epidemiology

Recent cancer statistics estimate that in 2019 there were 56,770 new cases of PC in the United States, which accounts for only 3.2% of all incident cancers (1,762,450) recorded.4

This is in comparison to 145,600 incident cases of colorectal cancer (8.2% of all incident cancers) or 271,270 new cases of breast cancer (15.4% of all incident cancers). PC is the third leading cause of cancer-related deaths in 2019 and is projected to be the cause of 45,750 deaths in 2019 (10.9 deaths per 100,000 people), which represents 7.54% of all cancer-related deaths projected for 2019 in the United States (606,880).4


Relative survival statistics are utilized to calculate the survival of an individual with PC as compared to an individual in the general population of the same age, race, and sex. The 5-year relative survival rate of PC is among the lowest of all cancers at just 9%.4 In contrast, the 5-year relative survival for all stages of prostate cancer combined is 99%; it is 92% for skin melanoma and 90% for female breast cancer. The survival rate of PC is much lower even when compared to other high-mortality cancers, such as lung (18% for the 5-year relative survival rate). Like most cancers, PC has a variable prognosis based on its stage at diagnosis. It has a relative 5-year survival rate of 34% among lesions localized to the primary site, as compared to the stages of nodal spread (11%) and distant metastasis (2.7%). Almost one-third (29%) of patients diagnosed with PC have regional spread at time of diagnosis, and 52% of patients diagnosed already have distant metastases. The survival rate is diminished given that the majority of cases are diagnosed in advanced stages.5 The survival rate of any cancer is determined by early diagnosis of precancerous and less advanced stages, as well as the efficacy of curative interventions (including either surgical resection and/or chemotherapy, including targeted therapy). While survival rates have generally improved for ...

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