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

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To the Editor:
We have read with great interest the recent article by Robb et al in Annals of Surgery.1 The French study group elegantly reanalyzed data of the FFCD 9901 trial.2 This randomized clinical trial compared survival after neoadjuvant chemoradiotherapy (nCRT) followed by surgery with surgery alone of patients with esophageal squamous cell carcinoma. The authors show that the number of resected lymph nodes and the number of positive nodes identified are reduced after nCRT compared with surgery alone.
Previous studies have shown that maximizing the number of resected nodes is still relevant for improving outcome after nCRT,3,4 whereas other cohort and population based studies have concluded the opposite.5–8 The study by Robb et al is the second study using data from a carefully conducted randomized controlled clinical trial and indicates that there is no association between the total number of resected nodes and survival. An earlier post hoc analysis of the Dutch randomized CROSS trial published in Annals of Surgery9 showed similar results.
In our opinion, the assertion made by the authors that their results do not challenge the indication for maximization of lymph node dissection during esophagectomy is, however, debatable. The analysis of the CROSS trial showed 2 important findings: (1) after nCRT, there was no association between the number of resected lymph nodes and survival; this was in sharp contrast to the group of patients in that trial who underwent surgery alone; and (2) after nCRT, there was no association between the total number of resected lymph nodes and the number of positive nodes. In our view these findings suggest that an extended lymphadenectomy is neither necessary for therapeutic nor for prognostic reasons. It would be of great interest if Robb et al could also present their data on the potential association between the number of resected nodes and the number of positive nodes.
Ultimately, to properly address the impact of surgical approach on lymph node retrieval and survival, a new randomized trial should be carried out comparing a transhiatal and transthoracic approach in the era of nCRT, preferably focusing on truly esophageal (Siewert type-1) cancers.

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