Pathological lymph node regression after neoadjuvant chemotherapy predicts recurrence and survival in esophageal adenocarcinoma: a multicenter study in the United Kingdom

Jonathan L. Moore, Michael Green, Aida Santaolalla, Harriet Deere, Richard P.T. Evans, Mona Elshafie, Anita Lavery, Damian T. McManus, Andrew 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 KellyCara R. Baker, Sacheen Kumar, Jesper Lagergren, William H. Allum, James A. Gossage, Ewen A. Griffiths, Heike I. Grabsch, Richard C. Turkington, Tim J. Underwood, Elizabeth C. Smyth, Rebecca C. Fitzgerald, David Cunningham, Andrew R. Davies, S. Puig, A. Chaudry, A. Jacques, N. Griffin, V. Goh, K. Owczarczyk, A Qureshi, M. Subesinghe, F. Chang, U. Mahadeva, B. Gill-Barman, S. George, M. Ong, J. Waters, M. Cominos, T. Sevitt, M. Hill, OCCAMS Consortium, The Guy's and St Thomas' Oesophago-gastric Research Group, The PROGRESS study group

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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 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.
Original languageEnglish
Pages (from-to)4522-4534
Number of pages13
JournalJournal of Clinical Oncology
Volume41
Issue number28
Early online date27 Jul 2023
DOIs
Publication statusPublished - 01 Oct 2023

Bibliographical note

Funding Information:
There were no study specific sources of funding. OCCAMS was funded by a Program Grant from Cancer Research UK (RG66287, A15874). OCCAMS2 was funded by a Program Grant from Cancer Research UK (RG81771/RG84119, A22720/A22131).

Publisher Copyright:
© American Society of Clinical Oncology.

Keywords

  • Cancer Research
  • Oncology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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