Pancreatic Adenocarcinoma, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology

Key guideline recommendations

1. Decisions on diagnosis, resectability and treatment of pancreatic cancer should be made with multidisciplinary consultation at high-volume centres with appropriate imaging. The panel unanimously prefers participation in clinical trials over standard treatment.

   Panel guiding principle

2. Genetic counselling and germline testing for inherited mutations are recommended at the initial evaluation of all patients (non-metastatic or metastatic); in metastatic disease, tissue confirmation preferably from a metastatic site, followed by germline testing and molecular profiling of tumour tissue.

   Panel recommendation

3. Most NCCN member institutions now prefer initial neoadjuvant therapy over upfront surgery in borderline resectable disease.

   Preference of most member institutions

4. Adjuvant therapy in patients who did not receive neoadjuvant therapy: capecitabine/gemcitabine (preferred) and mFOLFIRINOX (preferred); gemcitabine and fluorouracil/leucovorin (other recommended, category 1); continuous-infusion fluorouracil (other recommended). Capecitabine alone is also an option (category 2B).

   Category 1, preferred

5. Metastatic disease, first line in patients with good performance status (ECOG 0 to 1): FOLFIRINOX is a category 1 preferred option; mFOLFIRINOX is also a preferred first-line option; FOLFIRINOX and mFOLFIRINOX are also suitable for patients with BRCA1/2 and PALB2 mutations.

   Category 1, preferred

6. Nab-paclitaxel (albumin-bound paclitaxel)/gemcitabine is a category 1 preferred option for metastatic disease.

   Category 1, preferred

7. NALIRIFOX is recommended as first-line therapy for metastatic disease (category 1; by extension in locally advanced disease, category 2A). The panel acknowledges that high-level evidence supports the superiority of NALIRIFOX over nab-paclitaxel/gemcitabine, but this regimen has no clear advantage over FOLFIRINOX or mFOLFIRINOX.

   Category 1

8. Olaparib is the preferred targeted maintenance therapy for metastatic patients with a germline BRCA mutation whose disease has not progressed after 4 to 6 months of first-line platinum-based therapy.

   Preferred

9. Liposomal irinotecan + fluorouracil/leucovorin as subsequent therapy for patients with good/intermediate performance status previously treated with gemcitabine-based therapy (category 1 for metastatic disease; after fluoropyrimidine-based therapy without irinotecan, category 2A).

   Category 1

10. Daraxonrasib: based on survival improvement data (RASolute 302) and FDA approval, added as subsequent therapy for locally advanced, metastatic and post-surgical recurrent disease; based on panel discussion, also added as a first-line “useful in certain circumstances” option for metastatic disease.

    Subsequent therapy; first line: useful in certain circumstances

Study population

Clinical significance and place in guidelines

Limitations