Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma

OBJECTIVE: To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication. METHODS: Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups. RESULTS: Of 431 patients, 166 had eligible CA19-9 values. Median baseline CA19-9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19-9 dynamics during NT were analyzed by shape, direction, and normalization creating response types ("A-B-C-D-E"). Type A was "Always" decreasing to normalization, B "Bidirectional" with eventual normalization, C "Consistently" normal, D any "Decrease" without normalization, and E "Elevating" without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19-9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19-9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01). CONCLUSIONS: This novel A-B-C-D-E classification of CA19-9 dynamics during NT was associated with postresection outcomes more precisely than CA19-9 normalization alone.