Grade is a Dominant Risk Factor for Metastasis in Patients with Rectal Neuroendocrine Tumors.

BACKGROUND: Small (< 2 cm) and diminutive (< 1 cm) rectal neuroendocrine tumors (RNETs) are often described as indolent lesions. A large single-center experience was reviewed to determine the incidence of metastasis and the risk factors for its occurrence. METHODS: Cases of RNET between 2010 and 2017 at a single institution were retrospectively reviewed. The rate of metastasis was determined, and outcomes were stratified by tumor size and grade. Uni- and multivariable predictors of metastasis were identified, and a classification and regression tree analysis was used to stratify the risk for distant metastasis. RESULTS: The study identified 98 patients with RNET. The median follow-up period was 28 months. Of the 98 patients, 79 had primary tumors smaller than 1 cm, 8 had tumors 1 to 2 cm in size, and 11 had tumors 2 cm in size or larger. In terms of grade, 86 patients had grade 1 (G1) tumors, 8 patients had grade 2 (G2) tumors, and 4 patients had grade 3 (G3) tumors. Twelve patients developed metastatic disease. Both size and grade were associated with distant metastasis in the uni- and multivariable analyses, but when stratified by grade, size was predictive of metastasis only for G1 tumors (p < 0.001). Among the 12 patients with metastatic disease, 3 (25%) had diminutive primary tumors, and 9 (75%) had primary tumors 2 cm in size or larger. Diminutive tumors that metastasized were all G2. CONCLUSIONS: Patients with diminutive and small RNETs are at risk for metastatic disease. Tumor grade is a dominant predictor of dissemination. More rigorous staging, closer surveillance, or more aggressive initial management may be warranted for patients with G2 tumors, irrespective of size.

Efficacy of Peptide Receptor Radionuclide Therapy in a United States-Based Cohort of Metastatic Neuroendocrine Tumor Patients: Single-Institution Retrospective Analysis.

OBJECTIVES: The aim of this study was to analyze in a retrospective cohort study the outcomes of a United States-based group of metastatic neuroendocrine tumor (NET) patients who underwent peptide receptor radionuclide therapy (PRRT). METHODS: Twenty-eight patients from a single US NET Center were treated with PRRT. Toxicities were assessed using Common Terminology Criteria for Adverse Events version 4.03. Progression was determined by the Response Evaluation Criteria in Solid Tumors version 1.1. Univariate and multivariate Cox regression was performed to identify potential predictors of progression-free survival (PFS) and overall survival (OS). RESULTS: The median age at NET diagnosis was 56 years, 50% of the patients were male, 46% of NET primaries were located in the pancreas, 71% of tumors were nonfunctional, 25% were World Health Organization (WHO) grade III, and 20% had at least a 25% hepatic tumor burden. Anemia (36%) was the most common post-PRRT toxicity, followed by leukopenia (31%), nephrotoxicity (27%), and thrombocytopenia (24%). Median PFS was 18 months, and median OS was 38 months. Having a WHO grade III NET and receiving systemic chemotherapy prior to PRRT were found to be to independent predictors of shorter PFS and OS. CONCLUSIONS: Peptide receptor radionuclide therapy is an effective therapy in a US population. Progression-free survival and OS were better in WHO grade I/II NETs and when PRRT was sequenced prior to systemic chemotherapy.