Assessment of the Risk of Nodal Involvement in Rectal Neuroendocrine Neoplasms: The NOVARA Score, a Multicentre Retrospective Study

Abstract

Rectal neuroendocrine tumors (r-NETs) are rare tumors with overall good prognosis after complete resection. However, there is no consensus on the extension of lymphadenectomy or regarding contraindications to extensive resection. In this study, we aim to identify predictive factors that correlate with nodal metastasis in patients affected by G1–G2 r-NETs. A retrospective analysis of G1–G2 r-NETs patients from eight tertiary Italian centers was performed. From January 1990 to January 2020, 210 patients were considered and 199 were included in the analysis. The data for nodal status were available for 159 cases. The nodal involvement rate was 9%. A receiver operating characteristic (ROC) curve analysis was performed to identify the diameter (>11.5 mm) and Ki-67 (3.5%), respectively, as cutoff values to predict nodal involvement. In a multivariate analysis, diameter > 11.5 mm and vascular infiltration were independently correlated with nodal involvement. A risk scoring system was constructed using these two predictive factors. Tumor size and vascular invasion are predictors of nodal involvement. In addition, tumor size > 11.5 mm is used as a driving parameter of better-tailored treatment during pre-operative assessment. Data from prospective studies are needed to validate these results and to guide decision-making in r-NETs patients in clinical practice.

Comparison between endoscopic mucosal resection with a cap and endoscopic submucosal dissection for rectal neuroendocrine tumors

“…In our recent study [ 29 ], tumor size greater than 15 mm was considered to be an independent risk factor for lymph node metastasis in patients with colorectal neuroendocrine neoplasm, so 15 mm was used as the cut-off value to study the difference in endoscopic resection methods. We noticed that a recent report [ 30 ] suggested that tumor size greater than 11.5 mm was independent risk factor for lymph node metastases in patients with R-NETs. Maybe it's because of the different databases or the differences between the eastern and western populations.…”

Multiple rectal neuroendocrine tumors: An analysis of 15 cases and literature review

“…The rectal NEN with a maximum diameter of 1-2 cm has a lymph node metastasis rate of about 30% at the time of diagnosis, and about 40% in those ≥20 mm ( 27 , 34 ). In the latest multicenter retrospective study, diameter > 11.5 mm and vascular infiltration were independently correlated with nodal involvement ( 35 ). It is reported that 22.7% of patients with multiple rectal NETs whose diameter is less than 10mm have lymphatic metastasis ( 36 ).…”

European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for colorectal neuroendocrine tumours

“…Other risk factors for metastatic disease such as the presence of lymphovascular invasion, the presence of muscular invasion, histological non‐ L cell‐type and a high tumour grade have also been reported in different studies 9,29,31,35,36 . Correlation between tumour size and lymphovascular invasion has also been demonstrated with a tumour size ≥5 mm at higher risk of lymphovascular involvement than in tumours with a size <5 mm, 36 and predictive scores taking into account both, the tumour size and the lymphovascular involvement have been shown to provide an accurate assessment of the risk of metastatic lymph node involvement 37,38 …”

“…9,29,31,35,36 Correlation between tumour size and lymphovascular invasion has also been demonstrated with a tumour size ≥5 mm at higher risk of lymphovascular involvement than in tumours with a size <5 mm, 36 and predictive scores taking into account both, the tumour size and the lymphovascular involvement have been shown to provide an accurate assessment of the risk of metastatic lymph node involvement. 37,38 Computed tomography (CT) has limited value for the detection and characterisation of regional metastatic lymph nodes in patients with rNET. 39 Similarly to rectal adenocarcinoma, MRI with diffusionweighted imaging (DWI) is considered as the most sensitive imaging method for regional lymph node detection, detection of residual disease after incomplete resection, and the involvement of pelvic structures in more advanced tumours.…”