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Publications

Journal Article Ahead of print

PubMed: 42533309 DOI: 10.1097/SLA.0000000000007164

The Prognostic Impact of Lymph Node Yield Upon Survival in Esophageal Cancer Broken Down by Neoadjuvant Strategy: A Multicenter European Cohort Study.

Ann Surg

Authors: Nadia Guidozzi, Wing K Chou, Lorenzo Giorgi, Riadh Salem, Stijn Vanstraelen, Helena Gielen, Johnny Moons, Philippe Nafteux, Femke E Lammes, Jelle P Ruurda, Richard van Hillegersberg, Alban Todesco, Xavier B D'Journo, Alice Collizzolli, Barbara Ajazi, Simone Giacopuzzi, Maria Bencivenga, Sam Alhayo, Ella Seabourne, Ewen A Griffiths, Aram Abu Hejleh, Lars M Schiffmann, Christiane J Bruns, Giovanni M Garbarino, Andrea Pansa, Silvia Basato, Ophélie Bacoeur-Ouzillou, Caroline Gronnier, Sofie P G Henckens, Suzanne S Gisbertz, Rakesh Ahmed, Nithiesh Loganathan, Jessie A Elliott, Kirsty Cole, Youssef Ibrahim, Chanakya Anand, Philip H Pucher, Martin Skogar, Jakob Hedberg, Eloise Bonnin, Julie Veziant, Guillaume Piessen, Agnese Carresi, Silvia Battaglia, Francesco Puccetti, Riccardo Rosati, Fahad Murad, Fredrik Klevebro, Magnus Nilsson, Grard A P Nieuwenhuijzen … and 6 other authors

Affiliations

  • Nuffield Department of Surgical Sciences, Surgical Intervention Trials Unit, University of Oxford, Oxford, UK.
  • Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  • Department of Thoracic Surgery, University Hospital Leuven, Leuven, Belgium.
  • Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Department of Thoracic Surgery, North Hospital, Aix-Marseille University, Marseille, France.
  • General and Upper Gastrointestinal Surgery, Verona University, Verona, Italy.
  • Department of Upper Gastrointestinal Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Department of General, Visceral, Thoracic and Transplant Surgery, University Hospital of Cologne, Cologne, Germany.
  • Upper Gastrointestinal Surgery Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
  • Department of Visceral Surgery, Oesogastric Unit, Bordeaux University Hospital, Bordeaux, France.
  • Department of Surgery, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.
  • Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands.
  • The National Centre for Advanced Medical Imaging (CAMI), Trinity College Dublin, Dublin, Ireland.
  • Department of Surgery, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College Dublin, Dublin, Ireland.
  • Department of General Surgery, Portsmouth University Hospitals, NHS Trust, Portsmouth, UK.
  • Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
  • Department of Digestive and Oncological Surgery, CHU Lille, France.
  • Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Surgery and Oncology, Karolinska Institutet, Stockholm, Sweden.
  • Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden.
  • Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.

Abstract

OBJECTIVE

To establish a lymph node yield (LNY) change-point associated with improvements in overall survival (OS) and disease-free survival (DFS) in patients undergoing esophagectomy following neoadjuvant treatment for esophageal adenocarcinoma. Secondary endpoints include recurrence patterns and survival based on pathological staging.

SUMMARY BACKGROUND DATA

LNY has been associated with improved outcomes in esophageal cancer. The extent of lymphadenectomy following neoadjuvant treatment remains unclear.

METHODS

This multicenter European study included patients undergoing chemotherapy (CT) or chemoradiotherapy (CRT) followed by esophagectomy between 2018 and 2023. RA-CUSUM analysis identified change points between LNY and survival. Bootstrap resampling determined the optimal LNY, and multivariable Cox proportional hazards models analyzed LNY as continuous and categorical variables. A post hoc exploratory subgroup analysis was conducted in CT patients with optimal LNY compared with CRT irrespective of LNY. Recurrence patterns were assessed using the Fisher exact test.

RESULTS

A total of 2069 patients were included: 957 CT versus 1112 CRT. Median LNY was 32. CT data set: an optimal threshold of 25 nodes was identified (95% CI: 20-39). Categorical analysis using ≥25 nodes demonstrated 29% mortality reduction (HR: 0.714, P=0.0017). CRT data set: no significant LNY association across any endpoint. Continuous LNY showed a null effect (P=0.633), and categorical analysis showed no benefit (P=0.66). CT with ≥25 LNY had ∼44% lower mortality compared with CRT after adjustment for potential confounding variables (HR=0.563, P<0.001). Each positive LN increased the hazard for death by 7.3% in CT and 11.2% in CRT. Disease recurrence occurred in 32.7% of CT versus 38.3% of CRT (P=0.001).

CONCLUSION

On the basis of this data, there is a clear survival and recurrence benefit to performing a radical lymphadenectomy with a lymph node harvest of at least 25 nodes in patients who have received CT.

MeSH

Mortality, Lymph Nodes, Lymph Node Excision, Neoplasms, Cohort Studies, Lymph, Neoadjuvant Therapy, Therapeutics, Esophageal Neoplasms, Esophagectomy, General Surgery