Are Small Rectal Neuroendocrine Tumors Uniformly Low Risk?

Rectal neuroendocrine tumors (NETs) measuring less than 1 cm are generally regarded as low-risk lesions.^1-3 Most are detected incidentally during screening colonoscopy, and are completely removed by endoscopic resection. In routine practice, recurrence is uncommon after complete excision. Based on this clinical experience, current guidelines recommend limited follow-up in selected patients. The National Comprehensive Cancer Network (NCCN) guideline states that sub-centimeter rectal NETs that are completely resected with negative margins do not require routine surveillance.⁴ In contrast, the European Neuroendocrine Tumor Society (ENETS) guideline incorporates tumor grade into follow-up recommendations and advises imaging-based surveillance for grade 2 lesions, even when they are small and completely excised.⁵ These differences reflect two approaches to risk assessment: one mainly based on tumor size and margin status, and the other giving more weight to histologic grade.

The rationale for the NCCN framework is practical. When overall recurrence risk is extremely low, routine imaging or repeated endoscopic evaluation may expose patients to unnecessary procedures, anxiety, and cost. From a population perspective, limiting surveillance in clearly low-risk settings is reasonable and efficient. On the other hand, the ENETS position emphasizes that tumor biology does not always align strictly with size criteria. A small lesion can still demonstrate proliferative activity that suggests more aggressive potential. The tension between these views reflects a broader issue in oncology: should follow-up strategies be driven primarily by average risk in large cohorts, or by identifiable biological subgroups within those cohorts?

In this issue, Kim et al.⁶ provide important long-term outcome data that contribute meaningfully to this discussion. In a multicenter cohort of 860 patients with rectal NETs measuring 1 cm or less who underwent R0 resection without lymphovascular or perineural invasion, outcomes were analyzed with follow-up extending up to 9 years. The overall recurrence rate was 1.4%, confirming the favorable prognosis that has supported current limited-surveillance approaches. For the majority of patients, complete excision appears to provide durable disease control. However, the study also demonstrates that risk is not entirely uniform within this category. In multivariable analysis, histologic grade 2 and a mitotic count of at least 2 per 10 high-power fields were independently associated with recurrence. In contrast, tumor size within the sub-centimeter range, endoscopic resection technique, and endoscopic ultrasonographic depth were not significant predictors. Importantly, lymph node or hepatic metastases were observed only in patients with grade 2 tumors and increased mitotic activity. Although the number of events was small, these findings indicate that biological heterogeneity persists even among tumors commonly considered low risk.

Another notable finding is the timing of recurrence. Recurrence-free survival remained stable during the first 5 years after resection and declined thereafter, indicating that late recurrence can occur in a small proportion of patients. Although the overall recurrence rate remains low, this pattern suggests that early stability does not necessarily guarantee long-term safety. In clinical practice, the term “low risk” is often interpreted as minimal concern. However, the current findings indicate that low risk does not always imply uniform biological behavior. Do these observations warrant revision of existing guidelines? At present, such a step would likely be premature. The overall recurrence rate remains low, and most patients with small, completely resected rectal NETs achieve excellent long-term outcomes. The size- and margin-based strategy endorsed by NCCN appears broadly safe for the majority. At the same time, the association between grade 2 histology and recurrence supports the ENETS recommendation to consider tumor grade in follow-up planning. Rather than viewing these positions as conflicting, it may be more appropriate to recognize that they represent different thresholds for additional surveillance within a low-risk disease spectrum.

The more precise question, therefore, is not whether small rectal NETs are low risk—they are in most cases—but whether they are uniformly low risk. The data presented by Kim et al.⁶ suggest that they are not. Even within the group of sub-centimeter, R0-resected tumors, histologic grade identifies a subgroup with measurable long-term risk. This does not imply that aggressive surveillance is required for all patients; rather, it refines how the concept of low risk should be interpreted at the individual level.

If biological grade is to play a greater role in surveillance decisions, careful pathological assessment is essential. Accurate evaluation of mitotic count according to the World Health Organization 2019 criteria, based on a tumor area of 2 mm², and consistent application of grading standards are necessary for meaningful risk stratification.⁷ Interobserver variability and discordance between proliferative indices may otherwise result in inconsistent classification. Therefore, before surveillance strategies are expanded based on tumor grade, the reproducibility of grading in routine practice should be carefully considered. In summary, the study by Kim et al.⁶ reinforces the generally favorable prognosis of small, completely resected rectal NETs while highlighting the clinical relevance of histologic grade. Most patients remain at very low risk of recurrence. Nevertheless, grade 2 tumors with increased mitotic activity appear to represent a biologically distinct subgroup with a small but measurable long-term risk. These findings support continued and balanced discussion regarding how biological parameters should be integrated into follow-up strategies. As detection of small rectal NETs increases with widespread screening, future prospective studies with standardized pathological evaluation and long-term follow-up will be essential to define the optimal balance between oncologic safety and avoidance of unnecessary surveillance.