Biochemical, Radiographic, or Pathologic Response to Neoadjuvant Chemotherapy in Resected Pancreatic Cancer

Objective: To examine the optimal method of assessing response to neoadjuvant therapy (NAT) in operable pancreatic ductal adenocarcinoma (PDAC) patients. Summary of Background Data: PDAC response to NAT is measured with biochemical, radiographic and pathologic parameters, which can often be discordant with each other. Methods: PDAC patients undergoing resection after NAT at a single institution were retrospectively analyzed. Tumor response was assessed using pre-/post-NAT Carbohydrate Antigen 19-9 (CA 19-9) levels, radiographic decrease in tumor diameter, and pathologic Tumor Regression Grade (TRG). The association of these factors with overall survival (OS) was compared using Kaplan-Meier, Cox regression, and recursive partitioning analysis (RPA), a machine learning technique that can validate prediction models for complex hierarchical relationships. Results: From 2011 to 2022, 225 patients underwent pancreatectomy after NAT (Folfirinox, 70%; Gem+nab-paclitaxel, 19%; radiation, 18%). Almost half required vascular resection (portal vein, 39%; celiac axis 8%). Improved OS was observed after CA 19-9 decrease >50% (32 vs. 24 mo, P =0.0028), but not after major pathologic (TRG 0-1, P =0.067) or radiographic response (tumor diameter decrease >30%, P =0.89). However, RPA identified that the co-existence of biochemical and major pathologic response (achieved in 9% of patients) was associated with the longest OS (40 mo, P =0.0086). This optimal dual response combination was more commonly observed after neoadjuvant radiotherapy was used after systemic chemotherapy (45% vs. 11%, P <0.001). Conclusions: CA19-9 response to NAT alone is not enough to identify long-term post-resection PDAC survivors. The co-existence of CA19-9 and major pathologic response was predictive of the most optimal survival outcome.