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Endoscopic full-thickness resection for T1 colorectal cancer: here to stay!Referring to Zwager LW et al. p. 475–485
Even in an era of highly advanced imaging and resection techniques, treatment of T1 colorectal cancer remains a challenge. In clinical practice, we are faced with two problems. First, early cancer is often not recognized as such, and insufficient resection techniques are used, resulting in incomplete polypectomy. In these cases, it is difficult to judge whether there is residual tumor or not and scarring may hamper endoscopic re-therapy. Second, current guidelines recommend oncological surgical resection for patients at high risk of lymph node metastasis, whereas endoscopic treatment is considered to be curative for low-risk tumors. However, this risk assessment is done on the basis of histological features, and we currently do not have endoscopic criteria to reliably classify early tumors prior to treatment. For the patient, this may ultimately result in over- as well as undertreatment.
In this issue of Endoscopy, Zwager et al. present a detailed retrospective analysis of 330 cases undergoing endoscopic full-thickness resection (EFTR) for T1 carcinomas . These cases had been recorded in the nationwide Dutch EFTR registry; results of the total cohort, including other indications for EFTR, have been reported previously . The main outcomes of the current study were technical success, R0 resection, possibility of histological risk stratification, rate of curative resection, adverse events, and lesion recurrence. A total of 330 procedures were included, 132 involving primary treatment of suspected or proven T1 carcinoma and 198 involving EFTR after previous incomplete resection.
“The potential of EFTR as “excisional biopsy” includes the final determination of R0 status in cases of scar resection, as well as histological assessment of vascular, lymphatic, and submucosal invasion in cases of previously untreated lesions.”
Technical success (defined as macroscopic complete en bloc resection) was 87.0 % and is in line with most other studies on EFTR using the full-thickness resection device (Ovesco Endoscopy AG, Tübingen, Germany). More importantly, the R0 resection rate was as high as 85.6 %. This rate is comparable or even higher than that for endoscopic submucosal dissection (ESD) in Western countries  . Importantly, the R0 rates did not differ significantly between primary treatment (82 %) and resection of polypectomy scars (88 %). In a very similar study on EFTR for T1 cancer by our group, the R0 rates of the total cohort and especially of the primary treatment group were markedly lower (71.8 % and 60.9 %) . The reasons for this difference are unclear but it is very likely that more advanced lesions were included in our study. This highlights that patient selection is important for successful EFTR and that such criteria need to be defined in future studies. The lesions included in the study were relatively small (median diameter 15 mm for primary resection). At least one previous study indicated that chance of R0 resection may drop with increasing lesion size . I therefore agree with the authors, that T1 lesions with a diameter of > 20 mm should not be selected for EFTR. While more complex resection techniques such as ESD are excellent for the control of lateral margins, they are by definition limited to submucosa. As discussed by the authors, for lesions with deep submucosal invasion, this may result in incomplete resection . The study by Zwager et al. included a significant proportion of patients with sm2 /sm3 tumors and the R0 rate was still excellent. Recent studies have demonstrated that deep submucosal infiltration in the absence of other risk factors is associated with a low prevalence of lymph node metastasis . Hence, complete resection by EFTR may increase the chance for curative endoscopic treatment. Indeed, the authors report an increase of curative resection rates from 23.7 % to 60.8 % when excluding sm2/sm3 infiltration as a risk factor. However, this approach may not be in line with all international guidelines and needs further evaluation. Furthermore, the rate of curative resection may have been overestimated because other risk factors such as tumor budding were not consistently evaluated in the study.
Apart from demonstrating effective local treatment for low-risk tumors, the study results highlight the potential of EFTR as “excisional biopsy.” Compared with endoscopic mucosal resection or ESD, a full-thickness specimen is likely to fulfill the pathologist’s needs when it comes to histological assessment of invasive lesions. We do not have any comparative studies, but the study by Kuellmer et al. showed that the exact determination of risk status was possible in > 99 % of cases . This included final determination of R0 status in cases of scar resection, as well as histological assessment of vascular, lymphatic, and submucosal invasion in cases of previously untreated lesions.
Interestingly, only 15.3 % of patients in the study were referred for oncological resection due to the presence of one or more high-risk features. This further emphasizes that surgical resections may be avoided by use of EFTR. In the study, a significant proportion of patients who had finally been classified as high-risk after EFTR were not referred to surgery because of co-morbidities and/or patient preference. For patients unfit for surgery, EFTR may provide a minimally invasive local treatment; however, we do not have sufficient data on oncological outcome and therefore cannot finally conclude whether these patients will really benefit from this approach.
I would like to stress that as endoscopists we should not only aim to avoid unnecessary surgery. In the current study, histological data were available from 47 oncological resections, which had been performed due to high-risk features in the EFTR specimen. Residual tumor and/or lymph node metastasis was found in 11 cases, corresponding to a rate of 23.4 %. We are therefore strongly obliged to avoid undertreatment and send patients for oncological resection if indicated.
One limitation of the study by Zwager et al. is the registry design, with retrospective analysis of data and the lack of a control group. However, comparative studies on T1 colorectal cancer are very difficult to conduct and I doubt that we will see a randomized controlled study in the near future. Another major limitation is the shortness of follow-up. We ultimately need long-term data, not only on local recurrence, but also on oncological outcome.
New is not always better and we must await further data before we finally incorporate EFTR into our treatment algorithms and guidelines. However, based on our current knowledge, I think EFTR for T1 colorectal cancers is here to stay .
01 February 2022 (online)
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