Splenic flexure colon cancer may represent a distinct prognostic subtype associated with elevated systemic inflammation and impaired nutritional status.

Splenic flexure colon cancer (SFCC) is a rare gastrointestinal malignancy distinguished by its unique anatomical location and dual vascular supply. Nevertheless, its clinical behavior, prognostic outcomes, and underlying risk factors remain inadequately defined. A two-cohort study design enrolled 478 patients with stage II-III colon cancer. A colon cancer cohort (2012-2017) compared survival outcomes across tumor locations, while a separate SFCC-specific cohort (2012-2022) evaluated prognostic biomarkers in SFCC patients. A composite nutrition-inflammation integrating index (NII), derived from FPMLR and FPNLR, was developed and evaluated using Kaplan-Meier curves and Cox regression models. Significantly worse recurrence-free survival (RFS) and overall survival (OS) were observed in patients with SFCC or ascending colon cancer (ACC) compared with those with transverse or descending colon cancers (TCC or DCC), in both colon cancer cohort and SFCC cohort. SFCC was characterized by higher TNM stage, lymph metastasis status, large tumor-size, poor differentiation, and inflammation-nutrition imbalance relative to TCC and DCC. Multivariate Cox regression analysis identified the NII as an independent prognostic factor for OS in SFCC (adjusted HR = 3.834, 95%CI=1.452-10.122). Importantly, NII remained significantly associated with unfavorable clinical outcomes in subgroups, including patients with normal level of CA19-9, stage III disease, and those who underwent adjuvant chemoradiotherapy. SFCC may represent a potentially distinct prognostic subtype of colon cancer that appears to be associated with relatively aggressive pathological features and a persistently elevated systemic inflammatory state. The NII may serve as an exploratory indicator of the chronic inflammation-nutrition imbalance in these patients, and it may offer modest added value for risk stratification and individualized management. Further large-scale, multicenter prospective studies are warranted to validate these findings.