Prognostic significance of systemic inflammatory indices in squamous cell carcinoma of the anal canal: A retrospective cohort study

Background: Squamous cell carcinoma of the anal canal is a rare gastrointestinal malignancy with heterogeneous outcomes despite standardized chemoradiotherapy. Systemic inflammation has been implicated in tumor progression, and hematological indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation score (SII) have emerged as potential prognostic markers. This study aimed to assess the prognostic significance of pre-treatment inflammatory indices (NLR, PLR, SII) for disease-free survival (DFS) and overall survival (OS). Methods: This retrospective cohort study included 243 adult patients treated between 2006 and 2023 with combined chemoradiotherapy (5-fluorouracil and mitomycin C). Inflammatory indices were calculated from baseline laboratory values. Optimal cut-offs were determined using ROC analysis. Survival was evaluated using Kaplan-Meier curves and log-rank tests. Independent prognostic factors were identified through multivariate Cox regression. Results: Elevated indices were frequent (NLR ≥4: 56.8%; PLR ≥250: 47.7%; SII ≥980: 52.3%). Higher NLR, PLR, and SII were significantly associated with reduced DFS and OS (p < 0.05). In multivariate analysis, lymph node involvement (HR 1.94; p = 0.003), SII ≥980 (HR 2.01; p = 0.013), and absence of complete response (HR 5.67; p < 0.001) independently predicted poorer DFS. For OS, ECOG ≥1 (HR 2.70; p = 0.005), lymph node involvement (HR 3.45; p = 0.001), absence of complete response (HR 4.21; p < 0.001), NLR ≥4 (HR 2.47; p = 0.049), and PLR ≥250 (HR 3.28; p = 0.006) were independent predictors. Conclusion: Pre-treatment inflammatory indices provide significant prognostic information in squamous cell carcinoma of the anal canal and may enhance baseline risk stratification alongside established clinical factors.