Pathologic Lymph Node Regression After Neoadjuvant Chemotherapy Predicts Recurrence and Survival in Esophageal Adenocarcinoma: A Multicenter Study in the United Kingdom
J. Moore, Michael Green, Aida Santaolalla, Harriet Deere, Richard Evans, Mona Elshafie, Anita Lavery, Damian McManus, Andrew J. McGuigan, Rosalie Douglas, Joanne Horne, Robert Walker, Hira Mir, Monica Terlizzo, Sivesh K. Kamarajah, Mieke Van Hemelrijck, Nick Maisey, Ailsa Sita-Lumsden, Sarah Ngan, Mark Kelly, Cara Baker, Sacheen Kumar, Jesper Lagergren, William Allum, James Gossage, Ewen A. Griffiths, Heike I. Grabsch, Richard Turkington, Tim Underwood, Elizabeth Smyth, Rebecca C. Fitzgerald, David Cunningham, Andrew Davies, Susana Puig, A Chaudry, A. Jacques, Nyree Griffin, Vicky Goh, Kasia Owczarczyk, A. Qureshi, Manil Subesinghe, Fuju Chang, Ula Mahadeva, B. Gill‐Barman, Simi George, Mark Ong, John K. Waters, M. Cominos, T. Sevitt, Mark Hill, O. Hynes, G. Tham, William Knight, Jason Dunn, Sebastian Zeki
Abstract
PURPOSE: There is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma. METHODS: Multicenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS)-LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index. RESULTS: (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%). CONCLUSION: Pathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.