10Pancreatic
Snapshot. Almost all are PDAC (pancreatic ductal adenocarcinoma) — aggressive, usually presents late. Resectability defines everything: resectable / borderline resectable / locally advanced / metastatic, decided by the tumour's relationship to the SMA, SMV/portal vein, coeliac axis, and hepatic artery. CA 19-9 (a biliary/pancreatic marker) tracks disease (interpret only after relieving any biliary obstruction). Germline + tumour genetics — BRCA1/2, PALB2, MSI, NTRK — open maintenance and targeted options.
Workup
Pancreatic-protocol (multiphase) CT — defines vascular involvement → resectability — + EUS (endoscopic ultrasound) with biopsy — use FNB (core), not FNA — ⚠ a NEGATIVE biopsy does NOT exclude cancer: pancreatic adenocarcinoma is intensely DESMOPLASTIC (sparse tumour cells in dense stroma) so false negatives are common → REPEAT. ⚠ EUS not percutaneous — higher yield, and the percutaneous tract risks PERITONEAL SEEDING in a resectable patient. ⚠ If biopsy is negative, actively exclude AUTOIMMUNE (IgG4) PANCREATITIS — it mimics a head mass and patients get Whipples for it — plus neuroendocrine tumour, lymphoma and metastasis (classically RCC); CA 19-9 baseline; staging laparoscopy or PET in selected cases for occult metastases · germline testing (BRCA1/2, PALB2) + tumour MMR/MSI/NTRK at diagnosis.
Treatment by setting
| Setting | Treatment |
|---|
RESECTABLE
no arterial contact; ≤180° SMV/portal-vein contact without contour irregularity | Surgery — Whipple (pancreaticoduodenectomy) or distal pancreatectomy → Adjuvant mFOLFIRINOX (PRODIGE-24)
modified 5-FU + folinic acid + irinotecan + oxaliplatin — median OS 53.3 vs 35.5 months over gemcitabine Unfit for FOLFIRINOX → gemcitabine + capecitabine (ESPAC-4) Neoadjuvant mFOLFIRINOX — increasingly used, especially with HIGH-RISK features
markedly elevated CA 19-9, large primary, regional lymphadenopathy, excessive weight loss / pain ⚠ Still unproven for STANDARD resectable disease (Alliance A021806)
the phase III RCT built to answer perioperative vs upfront-surgery-then-adjuvant is unreported; neoadjuvant here remains an NCCN option, not a proven survival standard |
BORDERLINE RESECTABLE / LOCALLY ADVANCED
reconstructable venous involvement, or abutting-to-encasing arterial contact | Neoadjuvant FOLFIRINOX or gemcitabine + nab-paclitaxel ± chemoradiation → re-stage for resection Borderline converts to resection in a real minority
every one deserves reassessment at a high-volume pancreatic surgery centre — not a reflexive "inoperable" |
| METASTATIC | NALIRIFOX (NAPOLI-3)
liposomal irinotecan + 5-FU/leucovorin + oxaliplatin — median OS 11.1 vs 9.2 months over nab-paclitaxel/gemcitabine Or conventional FOLFIRINOX (fit, good performance status), or gemcitabine + nab-paclitaxel (less fit) Germline BRCA1/2-mutant, non-progressing on ≥16 weeks of platinum → maintenance olaparib (POLO) MSI-high → pembrolizumab |
Watch
FOLFIRINOX / NALIRIFOX are heavy — neutropenia, diarrhoea, neuropathy (needs a fit patient). Biliary obstruction → stent, and the TYPE of stent is a real decision, not admin: if any course of therapy is planned (neoadjuvant or palliative, i.e. months) use a SELF-EXPANDING METAL stent — plastic occludes at a median of ~47 days and buys cholangitis in the middle of chemotherapy (recurrent obstruction ~47% plastic vs ~0% metal); short plastic only if the patient is going straight to surgery; exocrine insufficiency → pancreatic enzyme replacement (plus dietitian from day one — weight loss is near-universal, and fitness is what decides FOLFIRINOX eligibility); high VTE (venous thromboembolism) risk; check DPYD (dihydropyrimidine dehydrogenase) before any fluoropyrimidine.