Description

• Adenocarcinoma of the exocrine pancreas (90% of pancreatic cancers) is the fourth most common cause of cancer death in the United States.
• Rarely curable: overall 5-year relative survival rate of 10.8%, the lowest of all cancers
• 60% occur in the head, 20% in the body and tail, and 20% diffusely involve the gland
• As few as 11% are localized at diagnosis. For localized, small cancers (<2 cm) with no lymph node metastases and no extension beyond the capsule, surgical resection has 5-year survival of about 41.6%.
• Majority of tumors have metastasized at diagnosis and are thus largely incurable and have a 5-year survival rate of 3%.
• Ampullary, duodenal, or distal bile duct tumors may mimic pancreatic carcinoma.

Epidemiology

During 2003 to 2007, median age at diagnosis was 70 years; rare <40 years; after 45 years of age, occurrence rises.

Incidence

• According to the American Cancer Society, an estimated 60,430 diagnoses and 48,220 deaths in the United States in 2021
• About 3.2% of all cancers and about 7% of cancer deaths; lifetime risk is about 1 in 64 (1.6%).
• More common in black and white races, 17 and 15.2 in 100,000 men and 14.3 and 11.7 in 100,000 women, respectively. Among Hispanic and Asian/Pacific Islanders, there is an incidence of 12.8 and 10.9 in 100,000 men and 11.1 and 9.3 in 100,000 women, respectively.

Prevalence
In the US, in 2018, ~83,777 people were living with pancreatic cancer.

Risk Factors

• Smoking: relative risk (RR) 2 to 3
• Diabetes: RR 2.1
• Prior partial gastrectomy or cholecystectomy: 2- to 5-fold increased risk 15 to 20 years after gastrectomy
• Familial aggregation/genetic factors: 5–10% of patients have a first-degree relative with the disease, which confers a 9-fold increase in risk versus the general population; subgroup may carry germline mutations of DNA repair genes (BRCA2).
• Hereditary chronic pancreatitis (autosomal dominant, highly penetrant): Cumulative risk by ages 50 and 75 years is 10% and 54%, respectively.
• Peutz-Jeghers syndrome: RR 30 to 40
• Familial atypical multiple mole and melanoma syndrome (p16): RR 10 to 20
• Hereditary nonpolyposis colon cancer (Lynch syndrome): RR 4
• Sporadic chronic pancreatitis
• Non–O blood type: RR 1 to 2
• High dietary fat, red meat, obesity, Helicobacter pylori
• Alcohol: in heavy consumers

General Prevention

• Clinicians should NOT screen average-risk individuals for pancreatic cancer.
• Screening should be considered in high-risk patients, including first-degree relatives of patients with pancreatic cancer with at least 2 affected genetically related relatives, in patients with genetic syndromes (Peutz-Jeghers syndrome, hereditary pancreatitis, patients with CDKN2A gene mutation, and patients with one or more first-degree relatives with pancreatic cancer with Lynch syndrome, and mutations in BRCA1, BRCA2, PALB2, and ATM genes).
• Screening in high-risk individuals should begin at age 50 years or <10 years the initial age of familial onset. Screening should be initiated at age 40 years in CKDN2A and PRSS1 mutation carriers with hereditary pancreatitis and at age 35 years in the setting of Peutz-Jeghers syndrome.

Commonly Associated Conditions

• Chronic pancreatitis, diabetes mellitus, cystic fibrosis
• KRAS mutations are present in >90% of pancreatic ductal adenocarcinomas.
• Mutation inactivation of tumor suppressors (SMAD4, p53, CDKN2A) allows for tumor progression.
• Subsets of familial pancreatic cancer involve germline cationic trypsinogen or PRSS1 mutations (hereditary pancreatitis), BRCA2 mutations (usually with hereditary breast-ovarian cancer syndrome), CDKN2 mutations (familial atypical mole, multiple melanoma), or DNA repair gene mutations (e.g., ATM and PALB2, apart from BRCA2).
• Majority of familial pancreatic cancers have no genetic underpinnings.
• Precursor lesions are potentially curable—pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasms.