Validity of Using Pathological Response as a Surrogate for Overall Survival in Neoadjuvant Studies for Esophageal Cancer: A Systematic Review and Meta-analysis.

Background: Pathological response is a critical factor in predicting long-term survival of patients with esophageal cancer after preoperative therapy. However, the validity of using pathological response as a surrogate for overall survival (OS) for esophageal cancer has not yet been established. In this study, a literature-based meta-analysis was conducted to evaluate pathological response as a proxy endpoint for survival in esophageal cancer. Methods: Three databases were systematically searched to identify relevant studies investigating neoadjuvant treatment for esophageal cancer. The correlation between pathological complete response (pCR) and OS were assessed using a weighted multiple regression analysis at the trial level, and the coefficient of determination (R²) was calculated. The research design and histological subtypes were considered in the performance of subgroup analysis. Results: In this meta-analysis, a total of 40 trials, comprising 43 comparisons and 55,344 patients were qualified. The surrogacy between pCR and OS was moderate (R² = 0.238 in direct comparison, R² = 0.500 for pCR reciprocals, R² = 0.541 in log settings). pCR could not serve as an ideal surrogate endpoint in randomized controlled trials (RCTs) (R² = 0.511 in direct comparison, R² = 0.460 for pCR reciprocals, R² = 0.523 in log settings). A strong correlation was observed in studies comparing neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy (R² = 0.595 in direct comparison, R² = 0.840 for pCR reciprocals, R² = 0.800 in log settings). Conclusions: A lack of surrogacy of pathological response for long-term survival at trial level is established in this study. Hence, caution should be exercised when using pCR as the primary endpoint in neoadjuvant studies for esophageal cancer. [ABSTRACT FROM AUTHOR]