15514 Background: Assessing the efficacy of treatment for locally advanced pancreatic cancer (LAPC) via CT is inadequate; radiologic responses are uncommon. We hypothesized that serum CA 19–9 level may serve as an alternative surrogate marker for treatment efficacy in LAPC. Methods: We conducted an analysis of 143 patients with LAPC treated at MDACC. Baseline, final, nadir and change in CA 19–9 levels were correlated with overall survival (OS). Factors included in our model were treatment regimen, grade, age, race and sex. Analysis was conducted using Kaplan-Meier product-limit survival probability estimates and log-rank tests. For the final multivariate Cox regression related to OS, non-significant variables were eliminated using a step-down fashion. Results: The median age was 62.4 years; 50.3% were male. 98 pts were treated on investigational protocols while 45 received non-protocol therapy. Treatments included induction chemotherapy (n=96), concurrent chemoradiation (n=116), and maintenance chemotherapy after chemoradiation (n=29). OS was 13.2 months (95% CI= 11.2, 17.6). On univariate analysis, age (p=0.02) and elevated final CA 19–9 (p<0.0001) correlated with worsened OS while decreased CA 19–9 (p<0.0001) and delivery of second line chemotherapy (p=0.02) correlated with improved OS. On multivariate analysis, the use of second-line chemotherapy correlated with an improved OS (HR 0.61, CI 0.38–0.98, p=.04) while an elevated post-treatment CA 19–9 correlated with worsened OS (HR 1.12, CI 1.05–1.19, p=.0004). In a Kaplan-Meier analysis patients with CA 19–9 improvement (n=90), a 50% decline correlated with improved OS (p=0.01). A Cox hazard ratio (univariate) for this group was 0.46 (CI 0.25, 0.85 p=.01). Conclusion: LAPC patients with elevated CA 19–9 levels after treatment have a poor prognosis; therefore, these patients should be considered for second-line chemotherapy. CA 19–9 decline by 50% or more is associated with an improved outcome. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, Merck, sanofi-aventis