The Comparison of Surgical Approaches in Locally Advanced Esophageal Cancer: Significant Insights but Clinical Fidelity Still to Be Delivered

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To the Editor:
We read with great interest the recent publication of Kutup et al1 describing the results of a large retrospective study of 2 high-volume centers concerning survival differences between transthoracic esophagectomy (TTE) and limited transhiatal esophagectomy (THE) in clinically (cT3) and pathologically (pT3) staged advanced tumors without neoadjuvant treatment.
It is a fact that these 2 surgical approaches are rarely compared among patients with clinically advanced esophageal cancer (EC). This adds to the value of this retrospective study, because 2 highly experienced centers for EC, performing the surgical procedures in a standardized manner, decided to analyze their results. But still, the fact that the chance for a randomized clinical trial on the patient was lost is a matter of criticism, because in this study, 72.9% of the patients underwent TTE and only 27.1% underwent THE procedure. And if we take into consideration that the patients undergoing TTE have a priori higher early postoperative mortality and morbidity rates,2 especially due to major pulmonary complications, which are responsible for 50% of the postoperative deaths,3 the conclusion that TTE results in a prolonged survival for both adenocarcinoma (AC) and squamous cell carcinoma (SCC) in node-positive patients is of profound clinical value, as far as the oncological effect of the approach is concerned.
Three points on the article, though, could also raise some important questions and offer a field of scientific debate.
First of all, it seems to be a discrepancy between the clinical staging of the disease and the final histological result. This discrepancy affects almost one-third of the study population [138 tumors (29.5%) were overstaged and 28 (6%) understaged].
Another issue to be discussed is the fact that the initial recruitment of the patients took place in the era where minimally invasive esophageal resections were not implied. As authors highlight, esophagectomy is a highly demanding procedure for patients in terms of perioperative complications and postsurgical impairments per se.1 In recent years, the introduction of minimal invasive techniques, both in abdominal and thoracic cavity, led to minimal trauma, less surgical stress and a significant reduction in the rate of postoperative pulmonary complications4–6 with equivalent oncologic outcomes between open and minimally invasive procedures.3,5,6 These approaches seem to be superior compared with THE as far as oncologic outcomes are concerned and superior compared with TTE as far as early mortality and morbidity is concerned. The need, though, for more randomized clinical trials on the value of minimally invasive esophageal resections is imperative.
Finally, to date, there is strong evidence to consider that locally advanced EC should be recommended for a multimodal treatment with a neoadjuvant chemotherapy7 or a combined chemoradiotherapy followed by surgery8 because of its grim prognosis. For locally advanced squamous cell carcinoma or for a part of adenocarcinoma, some centers have proposed treating with definitive chemoradiotherapy to avoid related mortality of surgery.8
The role of neoadjuvant chemoradiotherapy has been debated for several decades since in most randomized trials and meta-analyses, a marginal, if any, survival benefit from neoadjuvant chemoradiotherapy is suggested.9 If the patients with locally advanced EC are not candidates for preoperative therapy due to comorbidities or older age, then they should be treated with individual treatment modalities (eg, salvage esophagectomy) according to their performance status. But, including such patients in any study comparing standard surgical or conservative treatment could result in a systematic bias.
All in all, a real standard of care for locally advanced EC could not be easily defined, because accurate staging is not always feasible. Neoadjuvant therapy seems to have a role and TTE should be considered as the surgical “Holy Grail,” especially in patients with good performance status.

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