Risk of lymph node metastases and conditional survival in appendiceal neuroendocrine neoplasms

Alexander Troester; Lauren Weaver; Julia Frebault; Sarah L Mott; Lindsay Welton; Niccolo Allievi; Imran Hassan; Wolfgang Gaertner; Paolo Goffredo

doi:10.1016/j.surg.2024.109039

Risk of lymph node metastases and conditional survival in appendiceal neuroendocrine neoplasms

Surgery. 2025 Jan 4:180:109039. doi: 10.1016/j.surg.2024.109039. Online ahead of print.

Authors

Alexander Troester¹, Lauren Weaver², Julia Frebault³, Sarah L Mott⁴, Lindsay Welton⁵, Niccolo Allievi⁶, Imran Hassan⁷, Wolfgang Gaertner⁸, Paolo Goffredo⁹

Affiliations

¹ Department of Surgery, University of Minnesota, Minneapolis, MN. Electronic address: https://twitter.com/AlexTroesterMD.
² Department of Surgery, University of Minnesota, Minneapolis, MN. Electronic address: https://twitter.com/LWeaver_MD.
³ Department of Surgery, University of Minnesota, Minneapolis, MN. Electronic address: https://twitter.com/JuliaFrebault.
⁴ Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA.
⁵ Department of Surgery, University of Minnesota, Minneapolis, MN.
⁶ Department of Surgery, Papa Giovanni XXIII Hospital, Bergamo, Italy. Electronic address: https://twitter.com/AllieviNiccolo.
⁷ Department of Surgery, University of Iowa Hospitals & Clinics, Iowa City, IA.
⁸ Division of Colon & Rectal Surgery, Department of Surgery, University of Minnesota, Minneapolis, MN. Electronic address: https://twitter.com/GaertnerWB.
⁹ Division of Colon & Rectal Surgery, Department of Surgery, University of Minnesota, Minneapolis, MN. Electronic address: [email protected].

PMID: 39756338
DOI: 10.1016/j.surg.2024.109039

Abstract

Background: National Comprehensive Cancer Network guidelines recommend segmental colectomy for appendiceal neuroendocrine neoplasms >2.0 cm given the risk for lymph node involvement. However, additional clinicopathologic factors are associated with nodal metastases, and thus survival. Given dynamic changes of prognosis over time, conditional overall survival, the probability of surviving after a specific interval, has emerged as a novel oncologic outcome, but is scarcely available for appendiceal neuroendocrine neoplasms.

Methods: Adults with stage I-III appendiceal neuroendocrine neoplasms who underwent colectomy from 2010-2017 were identified in the National Cancer Database. Tumor histologies included neuroendocrine tumor grade 1, neuroendocrine tumor grades 2 and 3, neuroendocrine carcinoma, mixed neuroendocrine non-neuroendocrine neoplasm, and goblet cell carcinoma.

Results: Of 3,541 patients (median age 51 years, 43% male, 88% White), 16% had positive lymph nodes. Overall, 40% had neuroendocrine tumor grade 1, 4% neuroendocrine tumor grades 2 and 3, 10% neuroendocrine carcinoma, 12% mixed neuroendocrine non-neuroendocrine neoplasm, and 30% goblet cell carcinoma. Increasing depth of invasion, lymphovascular invasion, and increasing size were associated with lymph node metastases. Eighty-seven percent were alive at 2 years. Mortality after 2 years was associated with older age, mixed neuroendocrine non-neuroendocrine neoplasm and goblet cell carcinoma histology, penetration through serosa, nodal involvement, and tumor size.

Conclusions: In a national cohort, 1 in 6 patients had positive lymph nodes, which was associated with depth of invasion, lymphovascular invasion, and size. These findings indicate additional factors should be considered when determining the extent of surgical resection and surveillance to improve survival outcomes. Additionally, patients with penetration through serosa, and mixed neuroendocrine non-neuroendocrine neoplasm or goblet cell carcinoma histology had worse conditional overall survival, potentially reflecting more aggressive tumor biology that warrants closer follow-up.