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.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin whose incidence is rising. Multimodal treatment is crucial in the non-metastatic, potentially curable setting. However, the optimal management of patients with non-metastatic MCC is still unclear. In addition, novel insights into tumor biology and newly developed treatments (e.g., immune checkpoint inhibitors) that dramatically improved outcomes in the advanced setting are being investigated in earlier stages with promising results. Nevertheless, the combination of new strategies with consolidated ones needs to be clarified. We reviewed available evidence supporting the current treatment recommendations of localized MCC with a focus on potentially ground-breaking future strategies. Advantages and disadvantages of the different treatment modalities, including surgery, radiotherapy, chemotherapy, and immunotherapy in the non-metastatic setting, are analyzed, as well as those of different treatment modalities (adjuvant as opposed to neoadjuvant). Lastly, we provide an outlook of remarkable ongoing studies and of promising agents and strategies in the treatment of patients with non-metastatic MCC.