Rectal Neuroendocrine Tumors: Toward Translationally Informed Comparisons of ESD and TEM

We read with great interest the recent systematic review and meta-analysis by Dąbkowski et al, “Endoscopic submucosal dissection and transanal endoscopic microsurgery in the treatment of rectal neuroendocrine tumors: Systematic review and meta-analysis of observational studies,” which compared endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM) for rectal neuroendocrine tumors (rNETs) (1). This work represents an important effort to synthesize comparative data for 2 minimally invasive techniques in an area where high-quality evidence is limited. Nevertheless, several limitations warrant discussion. First, the meta-analysis included only observational studies. While understandable given the lack of randomized trials, these designs are highly prone to selection bias, particularly confounding by indication (2). Patients undergoing TEM may systematically differ from those undergoing ESD, potentially distorting estimates of R0 resection rates and recurrence. This limitation merits stronger emphasis. Furthermore, both ESD and TEM are technically demanding, with steep learning curves. Variation in operator experience and institutional volume across the included studies may have introduced additional unmeasured confounding, influencing complication rates and R0 resections. Second, although the authors stratified some analyses by tumor size (≤10 mm), they provided limited exploration of other sources of heterogeneity, such as tumor grade or invasion depth. These features are critical in treatment decisions and outcomes. ESD is generally favored for small, superficial lesions, whereas TEM is reserved for larger or deeper tumors; pooled estimates without further stratification risk obscuring these important clinical distinctions (3). Third, the pooled follow-up duration seemed short and inconsistent among studies, potentially underestimating recurrence rates. rNETs can recur late, and standardized long-term surveillance data are needed to draw firm comparisons. While acknowledging this limitation, the finding of higher recurrence after TEM despite higher R0 resection rates is intriguing. The higher recurrence after TEM may reflect residual microscopic disease or aggressive tumor subtypes inadequately captured in observational data. In addition, while procedural time and complications were summarized, functional outcomes—including sphincter preservation, continence, and quality of life—were not adequately addressed. These outcomes are highly relevant to patients given the anatomic challenges of rectal tumor resection (4). Future syntheses should incorporate these end points to support shared decision making. Beyond clinical outcomes, economic implications also warrant attention. Differences in procedural costs, hospital stay, and requirements for general anesthesia or intensive postoperative care between ESD and TEM have major implications for resource allocation, and a comprehensive evaluation should ideally include cost-effectiveness analyses (5). Finally, although the authors assessed publication bias using funnel plots, these plots are unreliable with fewer than 10 studies, as noted in Cochrane guidance (2), and this limitation should have been discussed more explicitly. Overall, Dąbkowski et al have highlighted an important clinical question. We encourage future prospective, well-controlled studies with standardized reporting of oncologic and functional outcomes to clarify the optimal approach for rNETs. Incorporating biomarker-driven stratification (e.g., Ki-67 index) in future studies could enhance personalization of rNET therapy. Incorporating patient-centered measures and health-economic analyses will be critical in refining treatment strategies for this rare but increasingly detected malignancy. Thank you for the opportunity to comment on this valuable work. CONFLICTS OF INTEREST Guarantor of the article: Shameer Tahir, MBBS. Specific author contributions: S.T. and H.S. jointly conceived the letter, drafted the text, and approved the final version for submission. Financial support: None to report. Potential competing interests: None to report.