Lymph node ratio, not nodal stage, predicts overall and disease-free survival in non-ampullary primary small intestine adenocarcinoma.

Lymph node ratio (LNR) has emerged as a strong prognostic indicator in colorectal cancer (CRC), but its significance in non-ampullary primary small intestine adenocarcinoma (SIA) has been only sparsely reported in the literature. Moreover, LNR has not been examined alongside key CRC histologic prognostic variables, including tumor budding (TB), desmoplastic reaction (DR), and tumor-infiltrating lymphocytes (TILs). Eighty-nine cases (mean age: 63 years, range: 20-88) of SIA were included from 2008 to 2023; most tumors arose in the duodenum (40%). Mean follow-up was 40.9 months (range: 0-189). The mean carcinoembryonic antigen (CEA) level was 38.4 ng/mL (range: 0.2-1183.9). Low-grade histology predominated (69%), and lymphovascular invasion was seen in 42% and perineural invasion in 16%. TB was low in 55%, intermediate in 30%, and high in 15%. DR was mature in 45%, intermediate in 43%, and immature in 12%. TILs were present in 34%. The average International TILs Working Group score was 29% (range: 0-80%). The mean LNR was 0.2, and 49% of cases were pN0. Most tumors were pT3 (54%) or pT4 (34%), and 12% were pM1. Only CEA level and LNR independently predicted disease-free survival (HR: 1.01; 95%CI 1.00-1.02; P = 0.010 and HR 14.64; 95%CI 1.82-117.59; P = 0.012, respectively), and LNR independently predicted overall survival (HR 14.55; 95%CI 1.76-120.06; P = 0.013). Higher LNR was significantly associated with adverse tumor characteristics, including features of the tumor microenvironment such as TB, DR, and TILs. LNR and pre-operative CEA level outperformed nodal stage and other histologic factors as prognostic markers in SIA.