Summary
High-tier evidence for neoadjuvant FOLFIRINOX in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) is currently limited to clinical guidelines and a single phase 3 randomized trial comparing mFOLFIRINOX against PAXG. The REDISCOVER, Korean, Chinese, and SEOM guidelines recommend neoadjuvant systemic chemotherapy for BR-PDAC to prioritize tumor biology and achieve R0 resection [1][2][3][6]. In the CASSANDRA phase 3 trial, mFOLFIRINOX was compared with PAXG in resectable and borderline resectable PDAC; while PAXG demonstrated superior event-free survival (EFS), mFOLFIRINOX remains a standard perioperative option referenced in guidelines [4].
Evidence
**CASSANDRA Trial (Phase 3, Randomized):** A randomized, open-label, 2×2 factorial phase 3 trial evaluated preoperative chemotherapy for stage I-III resectable and borderline resectable PDAC. Patients were assigned to mFOLFIRINOX or PAXG (cisplatin, nab-paclitaxel, capecitabine, gemcitabine) for 4 months. The primary endpoint was event-free survival (EFS). In the intention-to-treat population, PAXG prolonged median EFS compared with mFOLFIRINOX (16.0 months [95% CI 12.4-19.8] vs 10.2 months [8.6-13.5]; hazard ratio 0.63 [0.47-0.84]; p=0.0018) [4].
**REDISCOVER Guidelines (Clinical Guideline):** These guidelines present recommendations for BR-PDAC, prioritizing tumor biology over anatomical features. They highlight the need to define optimal timing and number of chemotherapy cycles prior to surgery but do not specify a single preferred regimen over others in the summary provided [2].
**SEOM Guidelines (Clinical Guideline):** State that neoadjuvant treatment represents the best option for achieving an R0 resection in borderline pancreatic cancer [1].
**Korean Clinical Practice Guideline (Clinical Guideline):** Includes recommendations for neoadjuvant treatment for patients with borderline resectable pancreatic cancer, integrating evidence-based research findings [3].
**Chinese Comprehensive Guidelines (Clinical Guideline):** Identify preoperative neoadjuvant therapy as the standard treatment for borderline resectable and locally advanced pancreatic cancer [6].
Caveats
The CASSANDRA trial included both resectable and borderline resectable patients, preventing a specific isolated efficacy analysis for BR-PDAC within that dataset [4]. The evidence base is heavily reliant on clinical guidelines rather than dedicated randomized trials for FOLFIRINOX specifically in the BR setting. Guidelines note significant areas requiring urgent research, including the optimal timing and number of chemotherapy cycles prior to surgery for BR-PDAC [2]. No high-tier data directly compares mFOLFIRINOX against other specific neoadjuvant regimens exclusively within the borderline resectable subset.