Pathologic Lymph Node Regression After Neoadjuvant Chemotherapy Predicts Recurrence and Survival in Esophageal Adenocarcinoma: A Multicenter Study in the United Kingdom
Authors: Moore Jonathan L. , Green Michael , Santaolalla Aida , Deere Harriet , Evans Richard P.T. , Elshafie Mona , Lavery Anita , McManus Damian T. , McGuigan Andrew , Douglas Rosalie , Horne Joanne , Walker Robert , Mir Hira , Terlizzo Monica , Kamarajah Sivesh K. , Van Hemelrijck Mieke , Maisey Nick , Sita-Lumsden Ailsa , Ngan Sarah , Kelly Mark , Baker Cara R. , Kumar Sacheen , Lagergren Jesper , Allum William H. , Gossage James A. , Griffiths Ewen A. , Grabsch Heike I. , Turkington Richard C. , Underwood Tim J. , Smyth Elizabeth C. , Fitzgerald Rebecca C. , Cunningham David , Davies Andrew R. ,   on behalf of The Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) study group, The Guy's and St Thomas' Oesophago-gastric Research Group, and The PROGRESS study group, Puig S. , Chaudry A. , Jacques A. , Griffin N. , Goh V. , Owczarczyk K. , Qureshi A , Subesinghe M. , Chang F. , Mahadeva U. , Gill-Barman B. , George S. , Ong M. , Waters J. , Cominos M. , Sevitt T. , Hill M. , Hynes O. , Tham G. , Knight W R C , Dunn J. M. , Zeki S. S. 
Published: July 2023

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 In total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (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.