Key Facts

Pancreatic cancer is the 10th most common cancer but the 5th leading cause of cancer death in the UK. Late presentation and aggressive biology contribute to its dismal prognosis.

Epidemiology

Incidence ~10,000 new cases/year in UK. Peak age 60-80 years. Slight male predominance (M:F ~1.3:1). Incidence is increasing. Lifetime risk ~1.5%.

Aetiology

• Smoking: Strongest modifiable risk factor (~2× increased risk)
• Chronic pancreatitis: ~5-10× increased risk (especially hereditary pancreatitis)
• Diabetes mellitus: Both risk factor and consequence (~50% of patients have new-onset DM at diagnosis)
• Obesity: ~20% increased risk
• Genetic: BRCA2 (~3-10× risk), Lynch syndrome, Peutz-Jeghers syndrome (~132× risk), familial atypical multiple mole melanoma (FAMMM)
• Alcohol: Indirect risk via chronic pancreatitis

Pathophysiology

• Pancreatic ductal adenocarcinoma: Arises from ductal epithelium; dense desmoplastic stroma limits drug penetration
• Key mutations: KRAS (~95%), TP53 (~75%), CDKN2A (~95%), SMAD4 (~55%)
• Precursor lesions: Pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm
• Head tumours obstruct CBD early → jaundice; body/tail tumours present late with pain and weight loss

Head of Pancreas (~60-70%)

• Painless obstructive jaundice: Dark urine, pale stools, pruritus
• Courvoisier's sign: Palpable, non-tender gallbladder in jaundiced patient
• Weight loss, anorexia
• New-onset diabetes mellitus
• Steatorrhoea (exocrine insufficiency)

Body/Tail (~30-40%)

• Back pain: Constant, dull, often worse lying down, better sitting forward
• Weight loss (marked)
• Presents late — often metastatic at diagnosis
• Splenic vein thrombosis → left-sided portal hypertension → gastric varices

Red Flags/Late Signs

• Trousseau's sign: Migratory thrombophlebitis — paraneoplastic
• Virchow's node (left supraclavicular lymphadenopathy)
• Sister Mary Joseph nodule (periumbilical metastasis)
• Ascites (peritoneal metastases)
• New-onset diabetes in patient >50 with weight loss — investigate for pancreatic cancer

Bloods

• LFTs: Obstructive pattern (raised bilirubin, ALP, GGT; mildly raised ALT/AST)
• CA 19-9: Elevated in ~80% (poor screening tool; useful for monitoring treatment response)
• FBC: Anaemia (chronic disease)
• HbA1c/glucose: New-onset diabetes
• Coagulation: May be deranged (vitamin K malabsorption from biliary obstruction)

Imaging

• CT pancreas (triple-phase): Investigation of choice — assessment of tumour size, vascular involvement (SMA, coeliac axis, portal vein/SMV), liver metastases, peritoneal disease
• MRCP: Biliary and pancreatic duct anatomy
• EUS (Endoscopic Ultrasound): FNA biopsy; best for small tumours; assesses vascular invasion
• PET-CT: If equivocal metastatic disease
• Staging laparoscopy: Before surgery — detects peritoneal metastases not visible on CT (~15-20%)

Special Tests

• ERCP: Therapeutic — biliary stenting for jaundice relief (if not proceeding to immediate surgery)
• Biopsy: EUS-FNA (tissue diagnosis for non-resectable disease before chemotherapy)

Surgical (Resectable Disease — ~10-20%)

• Head of pancreas: Whipple's procedure (pancreaticoduodenectomy) — resection of head of pancreas, duodenum, distal CBD, gallbladder, ± distal stomach
  • Perioperative mortality ~2-5% in specialist centres
  • Should be performed in high-volume centres
• Body/tail: Distal pancreatectomy ± splenectomy
• Adjuvant chemotherapy: Gemcitabine + capecitabine for 6 months (ESPAC-4 trial — median survival 28 months vs 25.5 months)

Non-Surgical

• Borderline resectable: Neoadjuvant chemotherapy (FOLFIRINOX) to downstage → reassess for surgery
• Locally advanced (unresectable): Chemotherapy (FOLFIRINOX or gemcitabine + nab-paclitaxel)
• Metastatic: Palliative chemotherapy — FOLFIRINOX (fit patients) or gemcitabine + nab-paclitaxel; median survival ~6-11 months
• Biliary stenting (ERCP): For jaundice palliation
• Palliative care: Early involvement — pain management (coeliac plexus block), nutrition (CREON for exocrine insufficiency), psychology

Referral Criteria

• Suspected pancreatic cancer — urgent 2WW referral (NICE NG12)
• MDT discussion at specialist HPB centre
• New-onset diabetes >50 with weight loss — urgent investigation

• Overall 5-year survival: ~7%
• Resected (Whipple's): Median survival ~20-28 months; 5-year survival ~15-20%
• Locally advanced: Median survival ~10-14 months
• Metastatic: Median survival ~3-6 months (without chemotherapy); ~6-11 months with FOLFIRINOX
• Adjuvant chemotherapy (ESPAC-4): Improves median survival by ~2.5 months
• 10-year survivors: Very rare — long-term cure is uncommon

Whipple's Procedure — What Is Resected

Key Trials