Predictors of Metastases in Rectal Neuroendocrine Tumors: Results of a National Cohort Study

BACKGROUND: Rectal neuroendocrine tumors are often found incidentally. Local excision alone has been advocated for lesions 2cm; however, the evidence base for this approach is limited. OBJECTIVE: Associations among tumor size, degree of differentiation, and presence of distant metastatic disease were examined. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted using a nationwide cohort. PATIENTS: A total of 4893 patients with rectal neuroendocrine tumors were identified in the National Cancer Database (2006-2015). MAIN OUTCOME MEASURES: Logistic regression analyses were used to evaluate associations among tumor size, degree of differentiation, and presence of regional and distant metastatic disease. Cut point analysis was performed to identify an optimal size threshold predictive of distant metastatic disease. RESULTS: Of patients included for analysis, 3880 (79.3%) had well-differentiated tumors, 540 (11.0%) had moderately differentiated tumors, and 473 (9.7%) had poorly differentiated tumors. On logistic regression, increasing size was associated with a higher likelihood of pathologically confirmed lymph node involvement (among patients undergoing proctectomy), and both size and degree of differentiation were independently associated with a higher likelihood of distant metastatic disease. The association between tumor size and distant metastatic disease was stronger for well-differentiated and moderately differentiated tumors (OR = 1.4; p < 0.001 for both) than for poorly differentiated tumors (OR = 1.1; p = 0.010). For well-differentiated tumors, the optimal cut point for the presence of distant metastatic disease was 1.15cm (area under the curve = 0.88; 88% sensitive and 88% specific). Tumors 1.15cm in diameter were associated with a substantially increased incidence of distant metastatic disease (72/449 (13.8%)). For moderately differentiated tumors, the optimal cut point was also 1.15cm (area under the curve = 0.87, 100% sensitive and 75% specific). LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: Tumor size and degree of differentiation are predictive of regional and distant metastatic disease in rectal neuroendocrine tumors. Patients with tumors >1.15cm are at substantial risk of distant metastasis and should be staged and managed accordingly. See Video Abstract at http://links.lww.com/DCR/A778.