Endoscopic mucosal resection as curative therapy for esophageal cancer is inappropriate and should be discouraged

The recent paper by Pech and colleagues [1] requires some critical comment regarding the oncologic adequacy of the proposed endoscopic therapy for early esophageal squamous cell cancer (SCC). The Wiesbaden group around Professor Ell are known for their vigorous advocacy of their approach to esophageal neoplasms with endoscopic mucosa resection (EMR), which they now characterize as “curative.” Introducing the topic, the authors state that EMR is already “…considered to be a safe and effective alternative treatment to radical surgery in cases where the neoplasia is intraepithelial or limited to the mucosal layer.” In the discussion they even state that EMR has been “established as a standard treatment for patients with early squamous-cell neoplasia over the past few years.”

However, the approach by Pech and colleagues neglects basic oncologic principles relating to cancer treatment. The readers of Endoscopy should be directed to a more realistic view regarding this topic.

It is generally accepted that complete R0 resection is a key feature of curative treatment for cancer, including early esophageal cancer [2]. R0 resection is a proven excellent surrogate marker for curative therapy, as it is the major prognostic factor in most studies. The endoscopic mucosa resections presented by Pech were predominantly R1 resections, with fewer than one third (24.6 %) being R0 resections.

This unacceptably low R0 rate is even more questionable, considering that the histopathologic evaluation of the specimen may be severely confounded because of the piecemeal technique, which was applied in the majority of patients (67.7 %). This is - in two ways - another severe violation of general principles for oncologic resections, which should still be respected: en bloc resection and a reasonable tumor-free resection margin are both required. Although the exact extent of the required resection margin in early esophageal SCC may be regarded as ill defined, it is clear that it must be larger than that which can be achieved with removal of small amounts of submucosa by means of EMR.

Another severe problem of the study is the highly selected nature of the study population, as only patients with high-grade intraepithelial neoplasia (HGIN) or T1 m lesions were included. Exclusion of pT1sm patients was done a priori (i) by means of EUS, (ii) by means of diagnostic EMR, and (iii) prior to analysis. The exact numbers of patients that were excluded are only presented incompletely. Pech et al. are thereby violating the principle of intention-to-treat analysis in many ways, making judgment of oncologic adequacy entirely impossible.

A further and possibly the most severe problem, where Pech and colleagues ignore well-established data regarding early esophageal SCC, concerns the rate of nodal involvement in this entity: The authors state that “These tumors have only a very low risk of lymph node metastasis.” This false expectation may be due to a limited view of the problem, focusing merely on the mucosa. Reviewing the surgical literature reveals detailed information that in early esophageal SCC a rate of 36.4 % nodal involvement must be expected [3].

Characterizing an oncologic procedure as “curative,” “safe”, and “appropriate” would require comparison of the overall survival achieved with this procedure with that achieved by the standard procedure. Recurrence-free survival is a bad surrogate marker for overall survival in esophageal cancer. We appreciate the fairness of Pech and colleagues, in that they tell at least their patients that “surgery is the current treatment of choice” and endoscopic resection is an “experimental therapy.” It is to be hoped that these patients get more detailed information about associated quality of life issues than do the readers of Endoscopy: The necessity for frequent re-evaluation and the unresolved oncologic problem are two issues which do not seem very appealing - from the oncologic as well as the psychological viewpoints.

In conclusion, the attention of the readers of Endoscopy should be directed to a more realistic view of the paper by Pech et al. It is currently not appropriate (and will possibly never be appropriate) to describe EMR of early esophageal squamous-cell cancer as “curative therapy,” and this approach should be strongly discouraged.

Competing interests: None

References

• 1 Pech O, May A, Gossner L. et al . Curative endoscopic therapy in patients with early esophageal squamous cell carcinoma or high-grade intraepithelial neoplasia.  Endoscopy. 2007;  39 30-35
• 2 Rahden B H A von, Stein H J. Barrett’s esophagus with high-grade intraepithelial neoplasia: observation, ablation or resection?.  Eur Surg. 2007;  39 249-254
• 3 Stein H J, Feith M, Bruecher B L. et al . Early esophageal cancer: pattern of lymphatic spread and prognostic factors for long-term survival after surgical resection.  Ann Surg. 2005;  242 566-573