Evaluation of the effects of neoadjuvant therapy on stage specific outcome estimates in patients with completely resected gastric cancer.

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139 Background: The current AJCC staging system for gastric cancer is based on pathologic staging and fails to take into consideration the effects of neoadjuvant therapy. We hypothesize that patients receiving neoadjuvant therapy have a worse outcome than patients with identical pathologic stage not receiving neoadjuvant therapy. Methods: We queried a prospectively maintained gastric cancer database for patients undergoing potentially curative resection for gastric adenocarcinoma between 1985 and 2012. Disease-specific survival (DSS) was estimated by Kaplan-Meier methods. The relationship between DSS and previously identified clinical risk factors was evaluated using Cox regression method. Results: A total of 2,752 patients were identified; of these 904 received neoadjuvant therapy and 1,848 received no neoadjuvant therapy. Patients receiving neoadjuvant therapy were younger (60.7 vs. 65.7 years) and more often male (72.9% vs. 62.4%). Their tumors were more often at the GE junction, but histology, differentiation, and rates of perineural and vascular invasion were similar. Of the 904 patients that received neoadjuvant treatment, 108 (11.9%) had a complete pathologic response. At a median follow up of 4.5 years, 5-year DSS is significantly worse for stage I patients (77% vs. 92%, p < 0.001) and stage III patients (18% vs. 28%, p = 0.025) receiving neoadjuvant therapy; there is a trend towards worse survival for stage II patients (60% vs. 67%, p = 0.059). Factors associated with inferior DSS include age, male sex, diffuse or mixed histology, tumor site, depth of invasion, tumor size, number of positive and negative lymph nodes, and neoadjuvant treatment. The effect of neoadjuvant treatment remains significantly associated with DSS (HR 1.30 [95%CI: 1.12-1.50], p = 0.0004) after adjusting for these other known risk factors. Conclusions: Patients receiving neoadjuvant therapy have a worse stage-specific survival compared to patients not receiving neoadjuvant treatment. The AJCC staging system should be updated to reflect this difference in survival in order to appropriately prognosticate based on pathologic staging.