Aggressive ductal adenocarcinoma with painless jaundice (head) or vague back pain (body/tail); poor prognosis.
Also known as: pancreatic cancer, pancreatic adenocarcinoma, PDAC
Overview
Malignant neoplasm of the pancreas; >85% are ductal adenocarcinomas (PDAC). Less common: cystic neoplasms (IPMN, MCN), neuroendocrine tumors, acinar cell carcinoma.
Epidemiology
~64,000 new cases and ~51,000 deaths annually in the US — 3rd leading cancer killer; projected to be 2nd by 2030. 5-year survival ~12% (recently improving). Most diagnosed at advanced stage. Median age at diagnosis 70.
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IPMN / mucinous cystic neoplasm — Cystic lesion; high-risk features (mural nodule, main duct >5 mm, jaundice, size >3 cm) warrant resection
Pancreatic pseudocyst — History of pancreatitis; absence of mural nodule or septations on EUS
Ampullary or duodenal carcinoma — Periampullary mass on EUS/ERCP
Diagnostic workup
Diagnostic criteria
Histologic confirmation by EUS-FNA preferred for non-resectable disease (allows molecular profiling). Resectable tumors may proceed to surgery based on imaging without pre-op biopsy if imaging is characteristic. AJCC TNM staging. Resectability classification: resectable, borderline resectable (vascular abutment), locally advanced (encasement of major vessels), metastatic.
Labs
LFTs — direct hyperbilirubinemia, elevated alk phos in obstructive (head) tumors
CBC, BMP, albumin (nutritional status)
Lipase usually normal (unlike acute pancreatitis)
CA 19-9 — elevated in ~80%; useful for monitoring response and recurrence; FALSE positive in cholestasis and Lewis-negative individuals (10% of population do NOT secrete CA 19-9)
CEA — less specific
Glucose, HbA1c (new diabetes association)
Coagulation (vitamin K deficiency in cholestasis)
Imaging
Multiphase pancreas-protocol CT (arterial and venous phases) — modality of choice for diagnosis, staging, and resectability assessment
MRI/MRCP — better characterization of pancreatic cystic lesions and indeterminate liver lesions
EUS — most sensitive for small lesions and lymph node assessment; tissue diagnosis via FNA
ERCP — therapeutic (stenting for biliary decompression); double-duct sign (dilated CBD and pancreatic duct) — classic for head tumor
PET-CT — selected cases for distant metastases
Diagnostic laparoscopy with peritoneal washings — recommended for body/tail tumors and high-risk head tumors before resection (occult peritoneal disease in 15-25%)
Diagnostic algorithm
Resectability Class
Imaging Criteria
Initial Management
Resectable
No arterial contact; ≤180° contact with SMV/PV without contour irregularity
Neoadjuvant chemo (increasingly) or upfront surgery + adjuvant chemo
Borderline resectable
Limited arterial contact (CHA, SMA <180°); SMV/PV reconstructable
Neoadjuvant chemo ± chemoradiation, then restage
Locally advanced (unresectable)
Encasement of SMA/celiac >180°; unreconstructable SMV/PV
Painless obstructive jaundice + palpable nontender gallbladder (Courvoisier sign) in older adult = pancreatic head cancer until proven otherwise.
Double-duct sign (dilated CBD and pancreatic duct) on cross-sectional imaging strongly suggests pancreatic head tumor.
CA 19-9 is useful for surveillance and treatment response but NOT for diagnosis (false positives in cholestasis, false negatives in Lewis-negative individuals).
New-onset diabetes after age 50, especially with weight loss, can be paraneoplastic — consider pancreatic imaging.
Tissue diagnosis: EUS-FNA preferred for indeterminate or unresectable lesions; CT-guided biopsy if EUS unavailable; resectable lesions with characteristic imaging may proceed to surgery without preop biopsy.
Whipple (pancreaticoduodenectomy) at high-volume centers reduces morbidity and mortality.
FOLFIRINOX or gemcitabine + nab-paclitaxel are standard first-line systemic regimens.
PRODIGE 24/CCTG PA.6: modified FOLFIRINOX adjuvant therapy significantly improves DFS and OS over gemcitabine in resected pancreatic cancer.
BRCA1/2 mutations occur in 5-9% of PDAC — universal germline testing recommended; opens platinum and PARP inhibitor options.
Universal germline genetic testing now recommended for ALL patients with PDAC (NCCN, ASCO).
Hereditary pancreatic cancer surveillance: EUS or MRI annually starting age 50 (or 10 yr before youngest affected relative) in patients with BRCA1/2, Lynch, Peutz-Jeghers, FAMMM, hereditary pancreatitis.
References
NCCN 2024 — NCCN Guidelines Version 2.2024 — Pancreatic Adenocarcinoma
PRODIGE 24 — Conroy T et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. NEJM 2018;379:2395-2406
POLO Trial — Golan T et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. NEJM 2019;381:317-327
ACG 2018 — Aslanian HR et al. AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals. Gastroenterology 2020;159:358-362
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