Standardized guidelines missing for treatment of GI large cell neuroendocrine carcinoma

Patients with gastrointestinal large cell neuroendocrine carcinoma (GILCNEC) show varying prognosis depending on the site of the primary tumour, suggests a study. Unfortunately, there remains no standardized consensus guidelines to manage GILCNEC.

The “American Joint Committee on Cancer (AJCC) Sixth Edition stage, surgery, and radiotherapy are independent prognostic factors of patients with GILCNEC,” according to the researchers.

This study obtained data on GILCNEC patients from the Surveillance, Epidemiology, and End Result (SEER) program. The research team then analysed prognostic factors by assessing the clinicopathological data and survival functions. They also performed multivariate analysis to identify independent risk factors associated with survival.

Overall, 531 individuals from the SEER database were included in the analysis. Patients had primary tumour in the following sites: esophagus (n=39, 7.3 percent), stomach (n=72, 13.6 percent), hepatobiliary (n=51, 9.6 percent), pancreas (n=97, 18.3 percent), small intestines (n=27, 5.1 percent), and colorectum (n=245, 46.1 percent). [Am J Clin Oncol 2024;47:363-372]

Notably, males were more likely to have esophagus, stomach, pancreas, and colorectum large cell neuroendocrine carcinoma (LCNEC) (p=0.001). Esophagus LCNEC was associated with poorer overall survival (OS) and small intestine LCNEC with better OS.

In multivariate analysis, the AJCC Sixth Edition stage, surgery, and radiotherapy were found to be prognostic indicators of OS in GILCNEC (p<0.05).

“Although surgery and radiotherapy can prolong the survival of patients with GILCNEC, their prognosis remains poor, and further prospectively designed multicentre clinical studies are needed to indicate the decision for clinicians,” the researchers said.

Treatment guidelines

Clinical practice guidelines for the management of GILCNEC do not exist yet. For patients with early-stage GILCNEC, the recommended treatment is surgical resection, but most patients are diagnosed at a mid-late stage. On the other hand, those with advanced disease are usually treated with first-line platinum plus etoposide or irinotecan.

Furthermore, studies on the diagnosis, management, treatment, and follow-up of GILCNEC are few and far in between. Recent case reports and small retrospective studies reported a poor prognosis for patients with GILCNEC. [Int J Surg Case Rep 2020;76:421-424; Case Rep Gastroenterol 2018;12:234-239; Arch Pathol Lab Med 2003;127:221-223]

“Before this study, no studies have compared survival outcomes and prognostic factors for GILCNEC based on the primary tumour site,” the researchers said.

LCNEC is a rare malignancy that has a poor prognosis. It is listed as one of the four variants of large cell carcinoma in the 2004 WHO Classification of Lung Tumors. [Eur J Cancer 2013;49:1975-1983; Gastroenterology 2007;132:899-904; Front Oncol 2021;11:653162]

“As understanding of this disease deepens, LCNEC is a more heterogeneous tumour group that shows different genetic conditions in different originating sites (this may, at least in part, be the result of differences in definitional features between organs and diagnostic difficulties),” the researchers said.