Tumor count and risk of lymph node metastasis in multiple rectal neuroendocrine tumors: an individual-level pooled...

Multiple rectal neuroendocrine tumors (RM-NETs) are a rare and underrecognized subtype of rectal neuroendocrine neoplasms. Although these tumors are usually small and well differentiated, their risk of lymph node metastasis (LNM) may be underestimated when tumor size is considered alone. Current guidelines do not distinguish RM-NETs from solitary lesions. This study investigated the association between tumor count and LNM in patients with RM-NETs.

A comprehensive literature search of PubMed, Embase, Web of Science, and Scopus was performed from database inception to September 30, 2025. Published case reports and case series describing two or more histologically confirmed rectal NETs were screened for eligibility, and one additional institutional case was included. Individual-level clinicopathological data were extracted and pooled. Receiver operating characteristic analysis was used to explore the discriminative ability of tumor count for LNM, and exploratory multivariable logistic regression was performed to identify factors associated with LNM.

A total of 46 patients were included, comprising 45 patients from 17 published studies and one institutional case. The median age was 57 years, and 80.4% of patients were male. Most tumors measured ≤ 10 mm (91.3%). LNM was identified in 8 patients (17.4%). ROC analysis suggested an exploratory threshold of approximately seven lesions. Patients with ≥ 7 tumors had a significantly higher incidence of LNM than those with fewer than 7 tumors, with rates of 46.7% and 3.2%, respectively. In exploratory multivariable analysis, tumor count ≥ 7 remained associated with LNM.

Tumor count may help identify patients with RM-NETs who are at increased risk of LNM. In this pooled analysis, the exploratory threshold of approximately seven lesions should be regarded as hypothesis-generating rather than as a definitive clinical cutoff. In patients with extensive multifocal disease, this finding may warrant closer nodal staging and multidisciplinary discussion, even when the maximum lesion size is small. Further validation in larger multicenter cohorts is warranted.

Not applicable.