Management of Appendiceal Neuroendocrine Tumors: Metastatic Potential of Small Tumors

Abstract

Background. Appendiceal neuroendocrine tumors (ANETs) are rare neoplasms usually discovered incidentally during appendectomy. ANETs \ 2 cm were thought to have no metastatic potential, and this dogma has driven management. Our aim is to evaluate the metastatic potential of ANETs \ 2 cm. Patients and Methods. A retrospective review was performed in a series of patients with ANETs who presented to our tertiary referral center from 1998 to 2019. Demographics, tumor characteristics, treatment, and clinical outcomes were evaluated. Results. In total, 114 patients were included. Median follow-up was 3.3 years (range, 21 days-15 years). At last follow-up, 34 (30%) patients had positive regional lymph nodes and 20 (18%) patients had metastatic disease. Of the 20 patients with metastatic disease, 11 (55%) had primary ANETs \ 2 cm. Patient age [ 40 years at diagnosis and ANETs with serosal invasion, lymphovascular invasion, intermediate tumor grade, or positive lymph nodes were features significantly more likely to present with metastatic disease. We found no difference in the rate of lymph node positivity, metastatic disease, or overall survival when patients were stratified by tumor size or type of resection (appendectomy vs. right hemicolectomy). On multivariate analysis, patients with metastatic disease at diagnosis had worse overall survival (HR = 24.4, p = 0.008).Conclusions. In our cohort, tumor size was not a significant risk factor for metastatic disease or worse outcome as many patients with ANETs \ 2 cm developed metastatic disease. Appendectomy alone was sufficient surgical management for most ANETs. Patients with risk factors for metastatic disease, regardless of primary ANET size, should be evaluated thoroughly and counseled for further management and surveillance.

Management of Appendiceal Neuroendocrine Tumors: Beyond Tumor Size

“…[5]. Our group recently published data that supports previous findings that RH showed no survival benefit over appendectomy in our patients with ANETs [6]; however, as in previous studies, a selection bias was present as patients with tumors greater than 2 cm (N=27/30, 90%) or tumors less than 2 cm but with aggressive features were offered RH (N=40/84, 48%) [6][7][8][9][10][11]. We also observed that 30% (N=34) of our group had regional disease and 18% had metastatic disease (N=20), which are much higher than the rates first reported by Moertel and colleagues [1].…”

“…We and other studies have questioned the effect of involved lymph nodes on ANET patient survival [6,7,9]. Our previous study showed that about a third of patients who had lymph node evaluation, either at the time of appendectomy or RH, had lymph node involvement [6]. The problem with lymph node evaluation in patients with ANETs is the lack of lymph nodes in most appendectomy specimens; therefore, patients may have involved regional lymph nodes with no evidence of disease progression by the end of our study.…”

“…Patients with ANETs, like all patients with cancer, fear disease spread, either to regional lymph nodes or distant sites. We and other studies have questioned the effect of involved lymph nodes on ANET patient survival [6,7,9]. Our previous study showed that about a third of patients who had lymph node evaluation, either at the time of appendectomy or RH, had lymph node involvement [6].…”

“…Since the completion of our published study consisting of 114 patients evaluated at our institution with a history of surgical resection of ANET, we collected an additional 36 patients as of October 1, 2020 [6]. Again, patients with synchronous or metachronous cancer, with goblet cell carcinoid of the appendix, or with inadequate clinic data were excluded.…”

“…In our previous paper, our aim was to evaluate the biological aspects and metastatic potential of ANETs and identify potential risk factors for metastatic disease and worse outcomes [6]. Our hypothesis was that in ANETs, characteristics such as small vessel invasion, grade, and depth of invasion were important prognostic factors and could delineate patients with aggressive disease at increased risk for disease spread.…”