Biochemical, Radiographic, or Pathologic Response to Neoadjuvant Chemotherapy in Resected Pancreatic Cancer: Which is Best?

Abstract

To examine the optimal method of assessing response to neoadjuvant therapy (NAT) in operable pancreatic ductal adenocarcinoma (PDAC) patients. PDAC response to NAT is measured with biochemical, radiographic and pathologic parameters, which can often be discordant with each other. 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. 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). 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.