What is your preferred neoadjuvant chemotherapy regimen for borderline resectable pancreatic ductal adenocarcinoma?

Agree while guidelines for the use of adjuvant therapy in resected PDAC are stronger (6 mos therapy for T1N0 tumors or greater), those for the use of neoadjuvant therapy are less clear. Some guidelines recommend not to use NAT unless there is a radiographic interface with mesenteric vessels, or in the high risk resectable tumors indicated in Dr. @Dr. First Last's response. That being said, the use of NAT in this setting is increasing with some centers recommending neoadjuvant therapy in all pote...

We typically use FOLFIRINOX as well and monitor with FDG PET, MRI, and CT. Metabolic response is associated with path response (not surprising) and also OS. The results from our group have been reported and extended duration of chemo as well as CA19-9 normalization and path response predicted better outcomes. We also routinely switch chemotherapy to GnP for lack of response, seemingly without detriment in survival. We still incorporate radiotherapy in the management of most of these patients.

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In borderline resectable disease, no randomized phase III trials have compared the approach of neoadjuvant therapy to the upfront surgery, and the best regimens to use in the borderline neoadjuvant setting are unknown. For patients who appear technically resectable but have poor prognostic features (markedly elevated CA 19-9; large primary tumors; large regional lymph nodes; excessive weight loss; extreme pain), consideration can be given to neoadjuvant therapy. Retrospective analyses have shown...

Based on the publication of (Reni et al., PMID 41275879), PAXG is a reasonable and evidence-supported neoadjuvant option for borderline resectable PDAC, and it has appropriately been incorporated into NCCN guidelines.

Overall survival data remain immature — EFS, while a meaningful endpoint, has not been validated as a surrogate for OS in neoadjuvant PDAC. The trial enrolled 260 patients across 17 Italian centers — a relatively modest sample size from a single country, raising questions about gene...