Cancer - pancreatic
Description
- Pancreatic ductal adenocarcinoma (PDAC) - >90% of pancreatic malignancy, arises from ductal epithelium
- Head of pancreas (~60-70%) - presents earlier with painless obstructive jaundice (bile duct compression); body/tail tumours present later, larger at diagnosis, often with pain/weight loss alone
- One of the poorest-prognosis solid tumours - most present with locally advanced or metastatic disease
Epidemiology
- Peak incidence 60-80 years; slight M>F
- Rising incidence globally; projected to become one of the leading causes of cancer death given limited progress on early detection
- ~80% present with unresectable (locally advanced or metastatic) disease at diagnosis
Aetiopathogenesis
- KRAS mutation in >90% - near-universal driver; TP53, CDKN2A, SMAD4 - common co-mutations
- Risk factors: smoking (strongest modifiable factor, ~2x risk), chronic pancreatitis, obesity, T2DM (especially new-onset in an older adult - can be a paraneoplastic manifestation of an occult tumour), heavy alcohol use
- Hereditary syndromes: BRCA1/2 (relevant for PARP inhibitor eligibility), Lynch syndrome, familial atypical multiple mole melanoma (CDKN2A/p16), Peutz-Jeghers, hereditary pancreatitis
- Precursor lesions: PanIN (pancreatic intraepithelial neoplasia), IPMN (intraductal papillary mucinous neoplasm - a surveillance/surgical entity in its own right given malignant potential)
Diagnosis
Clinical
- Head tumours - painless jaundice, pale stools, dark urine, pruritus, palpable non-tender gallbladder (Courvoisier's sign)
- Body/tail tumours - vague epigastric/back pain, weight loss, new-onset atypical diabetes, migratory thrombophlebitis (Trousseau's syndrome - paraneoplastic)
Investigations
- CT pancreas protocol (triple-phase, thin-slice) - defines resectability by assessing vascular involvement (SMA, coeliac axis, portal/SMV) - the key staging determinant
- CA19-9 - not diagnostic alone (low specificity, falsely low in Lewis-antigen-negative individuals, falsely elevated with biliary obstruction) but useful for monitoring treatment response/recurrence once elevated at baseline
- Tissue diagnosis (EUS-guided FNA/biopsy) before starting neoadjuvant therapy or for unresectable/metastatic disease
- Germline BRCA1/2 testing - recommended for all patients with pancreatic cancer given prognostic/PARP inhibitor treatment implications, not only those with a strong family history
Management
By resectability category - the key branch point
| Category | Definition | Approach |
|---|---|---|
| Resectable | No arterial contact, no/minimal venous involvement | Surgery -> adjuvant chemotherapy (mFOLFIRINOX preferred if fit, or gemcitabine-based) |
| Borderline resectable | Limited vascular involvement, technically challenging | Neoadjuvant chemotherapy (+/- chemoradiation) first, then reassess for surgery |
| Locally advanced (unresectable) | Significant arterial encasement | Systemic chemotherapy +/- chemoradiation; occasional conversion to resectable |
| Metastatic | Distant spread | Systemic chemotherapy, palliative intent |
A. Resectable disease
- Surgical resection (Whipple procedure for head tumours, distal pancreatectomy for body/tail) followed by adjuvant mFOLFIRINOX (in fit patients) - improves survival over gemcitabine-based adjuvant regimens
B. Borderline resectable/locally advanced
- Neoadjuvant FOLFIRINOX (or gemcitabine/nab-paclitaxel) - downstages disease, improves R0 resection rates and survival versus upfront surgery in this group
C. Metastatic disease
- FOLFIRINOX or gemcitabine + nab-paclitaxel - the two standard first-line regimens in fit patients, chosen by performance status/comorbidity (FOLFIRINOX more toxic, generally reserved for good performance status)
- PARP inhibitor (olaparib) maintenance - for germline BRCA-mutated metastatic disease that has not progressed on first-line platinum-based chemotherapy
- Second-line options (e.g. nanoliposomal irinotecan + 5-FU/leucovorin) after first-line progression
D. Palliative/supportive
- Biliary stenting (ERCP) for obstructive jaundice - relieves symptoms, often needed before chemotherapy can start
- Pain management (coeliac plexus block for refractory pain), pancreatic enzyme replacement for exocrine insufficiency, nutritional support
Associations
- Smoking, chronic pancreatitis, obesity, T2DM
- BRCA1/2, Lynch syndrome, CDKN2A/familial melanoma, Peutz-Jeghers, hereditary pancreatitis
- Trousseau's syndrome (migratory superficial thrombophlebitis) and elevated VTE risk generally - pancreatic cancer carries among the highest cancer-associated thrombosis rates
- IPMN - premalignant, requires its own surveillance pathway
Natural history & complications
- Overall prognosis remains poor - 5-year survival ~10-13% across all stages, reflecting late presentation
- Resected disease still recurs in the majority despite adjuvant therapy - local and distant (liver, peritoneum) relapse both common
- Metastatic disease - median survival ~1 year with modern chemotherapy, better than a decade ago but still limited
- BRCA-mutated tumours - somewhat better chemosensitivity (platinum) and now a maintenance therapy option (olaparib), a meaningful prognostic subgroup
🔒
6 more sections, plus exam facts
Premium unlocks every note across every specialty, and the full exam fact library behind it.
Get premium access