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

OBJECTIVE: To examine the optimal method of assessing response to neoadjuvant therapy (NAT) in patients with operable pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: PDAC response to NAT is measured with biochemical, radiographic, and pathologic parameters, which can often be discordant with each other. METHODS: Patients with PDAC undergoing resection after NAT at a single institution were retrospectively analyzed. Tumor response was assessed using pre/post-NAT carbohydrate antigen 19-9 (CA19-9) levels, radiographic decrease in tumor diameter, and pathologic tumor regression grade. The association of these factors with overall survival (OS) was compared using Kaplan-Meier, Cox regression, and recursive partitioning analysis, 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%; gemcitabine + nab-paclitaxel, 19%; radiation, 18%). Almost half required vascular resection (portal vein, 39%; celiac axis 8%). Improved OS was observed after CA19-9 decrease >50% (32 vs 24 months, P = 0.0028), but not after major pathologic (tumor regression grade: 0-1, P = 0.067) or radiographic response (tumor diameter decrease >30%, P = 0.89). However, recursive partitioning analysis identified that the coexistence of biochemical and major pathologic response (achieved in 9% of patients) was associated with the longest OS (40 months, 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 postresection PDAC survivors. The coexistence of CA19-9 and major pathologic response was predictive of the most optimal survival outcome.