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Impact of Neoadjuvant Chemoradiation on Lymph Node Status in Esophageal Cancer: Post hoc Analysis of a Randomized Controlled Trial

Robb, William B. MD*,†,‡; Dahan, Laetitia MD, PhD§; Mornex, Françoise MD; Maillard, Emilie MS; Thomas, Pascal-Alexandre MD**; Meunier, Bernard MD††; Boige, Valérie MD‡‡; Pezet, Denis MD, PhD§§; Le Brun-Ly, Valérie MD¶¶; Bosset, Jean-François MD, PhD‖‖; Mabrut, Jean-Yves MD, PhD***; Triboulet, Jean-Pierre MD*,‡; Bedenne, Laurent PhD†††; Seitz, Jean-François MD§; Mariette, Christophe MD, PhD*,†,‡on behalf of the Fédération Française de Cancérologie Digestive, Société Française de Radiothérapie Oncologique, Union des Centres de Lutte Contre le Cancer, Groupe Coopérateur Multidisciplinaire en Oncologie, French EsoGAstric Tumour working group, Fédération de Recherche En Chirurgie

doi: 10.1097/SLA.0000000000000991
Original Articles

Objective: The study objectives were to analyze the impact of the number of lymph nodes (LNs) reported as resected (NLNr) and the number of LNs invaded (NLNi) on the prognosis of esophageal cancer (EC) after neoadjuvant chemoradiotherapy.

Background: Pathological LN status is a major disease prognostic factor and marker of surgical quality. The impact of neoadjuvant chemoradiation (nCRT) on LN status remains poorly studied in EC.

Methods: Post hoc analysis from a phase III randomized controlled trial comparing nCRT and surgery (group nCRT) to surgery alone (group S) in stage I and II EC (NCT00047112). Only patients who underwent surgical resection were considered (n = 170).

Results: nCRT resulted in tumoral downstaging (pT0, 40.7% vs 1.1%, P < 0.001), LN downstaging (pN0, 69.1% vs 47.2%, P = 0.016), and reduction in the median NLNr [16.0 (range, 0–47.0) vs 22.0 (range, 3.0–58.0), P = 0.001] and NLNi [0 (range, 0–25) vs 1.0 (range, 0–25), P = 0.001]. A good histological response (TRG1/2) in the resected esophageal specimen correlated with reduced median NLNi [0 (range, 0–10) vs 1.0 (range, 0–4), P = 0.007]. After adjustment by treatment, NLNi [hazards ratio (HR) (1–3 vs 0) 3.5, 95% confidence interval (CI): 2.3–5.5, and HR (>3 vs 0) 3.5, 95% CI: 2.0–6.2, P < 0.001] correlated with prognosis, whereas NLNr [HR (<15 vs ≥15) 0.95, 95% CI: 0.6–1.4, P = 0.807 and HR (<23 vs ≥23) 1.4, 95% CI: 0.9–2.0, P = 0.131] did not. In Poisson regression analysis, nCRT was an independent predictive variable for reduced NLNr [exp(coefficient) 0.80, 95% CI: 0.66–0.96, P = 0.018].

Conclusions: nCRT is not only responsible for disease downstaging but also predicts fewer LNs being identified after surgical resection for EC. This has implications for the current quality criteria for surgical resection.

Neoadjuvant chemoradiation not only downstages esophageal cancer but also reduces the number of lymph nodes being resected. This has an impact on the current standards and quality criteria for surgical resection.

*SIRIC ONCOLille and Université Lille-Nord de France

Inserm, UMR837, Team 5 “Mucins, epithelial differentiation and carcinogenesis” Jean Pierre Aubert Research Center, Lille, France

Department of Surgical Oncology, Lille University Hospital, Lille, France

§Department of Digestive Oncology, La Timone Hospital, Aix-Marseille University, Marseille, France

Department of Radiotherapy, Pierre-Bénite Hospital, Lyon, France

Department of Biostatistics, Fédération Française de Cancérologie Digestive, Dijon, France

**Department of Thoracic Surgery, Hôpital Nord, Marseille, France

††Department of Digestive Surgery, University Hospital, Rennes, France

‡‡Department of Oncology, Gustave Roussy, Villejuif, France

§§Department of Oncology, University Hospital, Clermont-Ferrand, France

¶¶Department of Gastroenterology, University Hospital, Limoges, France

‖‖Department of Radiotherapy, University Hospital of Besançon, Besançon, France

***Department of Digestive Surgery, Croix-Rousse University Hospital, Lyon, France

†††Department of Gastroenterology, University Hospital of Dijon, Dijon, France.

Reprints: Christophe Mariette, MD, PhD, Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Regional University Hospital Center, Place de Verdun, 59037, Lille Cedex, France. E-mail: christophe.mariette@chru-lille.fr.

Collaborators are listed at the end of the article.

Disclosure: The FFCD 9901 randomized trial was supported by a grant, Programme Hospitalier pour la Recherche Clinique (1998/98-1916), from the French National Cancer Institute. The study promoter was the Lille University Hospital. The authors have no conflict of interests to declare.

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