Background: The optimal cutoffs for carbohydrate antigen 19-9 (CA19-9) response after neoadjuvant therapy (NT) for pancreatic adenocarcinoma (PDAC) are not well characterized. This study aimed to analyze the relationship of serum CA19-9 to other markers of response and to identify thresholds correlating to outcomes. Methods: A retrospective review of resected PDAC patients from 2010 to 2017 at an academic tertiary referral center was conducted. Results: The analysis enrolled 250 subjects. Normalization and multiple cutoff points for CA19-9 response were assessed. Normalization was not associated with improved survival (35.17 vs. 29.43 months; p = 0.173). Although a response 45% or higher was associated with longer survival (35 vs. 20 months; p = 0.018), a response of 85% or higher was optimal (55.7 vs. 25.97 months; p < 0.0001). A response of 85% or higher remained a strong independent predictor of survival [hazard ratio (HR), 0.47; p = 0.007]. Subjects with a response of 85% or higher had received more NT cycles [3 (range 2–6) vs. 3 (range 2–4) cycles; p = 0.006] and fewer adjuvant cycles [4 (range 3–6) vs. 5 (range 3–6) cycles; p = 0.027]. Reduction in T-size correlated with a drop in CA19-9 and a size reduction of 25% or higher (56.97 vs. 28.17 months; p = 0.016) improved survival. A serum CA19-9 response of 85% or higher was a strong independent predictor of a reduction in T-size of 25% or higher (HR 2.40; p = 0.007). Conclusion: A CA19-9 response of 85% or higher is the optimal threshold for predicting survival. It is predictive of T-size reduction. Future NT trials should incorporate CA19-9 response as an end point.
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