Resectable Pancreatic Cancer with CA19-9 > 500 U/mL: A Biological Indicator for Survival Benefit with Intensive Neoadjuvant Chemotherapy.

Background: While anatomical resectability guides pancreatic cancer treatment, carbohydrate antigen (19-9 (CA19-9) serves as a biological indicator of disease burden. Current guidelines suggest considering neoadjuvant chemotherapy (NAC) for cases with markedly elevated CA19-9, but specific threshold values and treatment strategies remain undefined. This retrospective study aimed to evaluate the efficacy of intensive NAC using gemcitabine plus nab-paclitaxel or fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) for anatomically resectable pancreatic cancer with elevated CA19-9 (> 500 U/mL).

Methods: We analyzed patients with anatomically resectable pancreatic cancer and CA19-9 > 500 U/mL treated between 2014 and 2022. Initial planned treatments were either 4-month intensive NAC followed by surgery (NAC group) or upfront surgery (UPS group). Survival outcomes were evaluated using retrospective intention-to-treat analysis.

Results: Among 184 included patients, 46 received NAC and 138 underwent upfront surgery. The NAC group demonstrated significantly improved overall survival compared with the UPS group (median 52.7 vs. 22.7 months, P < 0.001). Resection rates were 89.1% and 76.1% in the NAC and UPS groups, respectively. Among resected cases, the NAC group achieved higher lymph node-negative resection rates (53.7% vs. 23.8%, P < 0.001) and better post-resection CA19-9 normalization rates (75.6% vs. 56.1%, P = 0.037). Survival benefits were maintained even in cases with CA19-9 > 2000 U/mL (median OS 52.7 vs. 18.9 months, P = 0.025).

Conclusions: CA19-9 > 500 U/mL serves as an effective indicator for implementing intensive NAC in anatomically resectable pancreatic cancer. This biomarker-based strategy effectively extracts the beneficial group from NAC, prolonging survival outcomes through better systemic disease control.