Pancreatic Cancer

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Basics

Description

  • Adenocarcinoma of the exocrine pancreas (90% of pancreatic cancers) is the fourth most common cause of cancer death in the United States and the ninth most common cancer in women.
  • Rarely curable: overall 5-year relative survival rate of 7.7%
  • 60% occur in the head, 20% in the body and tail, and 20% diffusely involve the gland.
  • As few as 9% 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 29%.
  • Majority of tumors have metastasized at diagnosis and are thus, largely incurable and have a 5-year survival rate of 2–3%.
  • In apparently resectable disease, 20–40% have unresectable lesions at surgery.
  • Ampullary, duodenal, or distal bile duct tumors may mimic pancreatic carcinoma and are more likely to be resectable and curable.
  • For advanced or unresectable cancers, survival is <1% at 5 years; most patients die within 1 year.

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 55,440 diagnoses and 44,330 deaths in the United States in 2018
  • About 3% of all cancers and about 7% of cancer deaths
  • Lifetime risk is about 1 in 65 (1.5%).
  • More common in black and white races, 16.7 and 10.3 in 100,000 men and 14.4 and 10.3 in 100,000 women, respectively. Among Hispanic and Asian/Pacific Islanders, there is an incidence of 10.9 and 8.3 in 100,000 men and 10.1 and 8.3 in 100,000 women, respectively.

Prevalence
In 2008 in the United States, ~34,600 men and women (16,811 men and 17,846 women) were alive who had a history of pancreatic cancer.

Risk Factors

  • Smoking: relative risk (RR) 2 to 3; correlates with amount smoked
  • Diabetes: RR 2.1 (95% CI 1.6–2.8); 1 in 6 become diabetic within 6 months before diagnosis.
  • 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: Recent data indicate a modest increase in risk confined to heavy alcohol consumers.
  • Coffee intake and NSAID use NOT regarded as risk factors

General Prevention

No effective screening modality exists to detect early cancer. Even with a strong family history or predisposition syndromes, use and cost-effectiveness of screening are unclear.

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.

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