Divergent Prognostic Impact of Histopathological Features and Combined Hematological-Biochemical Indices in Rectal Versus Colorectal Cancer: A Single-Center Study.

Background: Colorectal cancer is frequently analyzed as a single disease entity despite recognized biological and clinical differences between colon and rectal tumors. This study investigated whether systemic inflammatory and nutritional indices demonstrate similar prognostic value in a pooled colorectal cancer cohort and in rectal adenocarcinoma analyzed separately. Methods: A predefined subgroup analysis of a previously established single-center cohort of surgically treated patients with long-term follow-up was performed. Prognostic associations of clinical, hematological, biochemical, and histopathological variables were evaluated in the overall colorectal cancer cohort and subsequently in patients with rectal adenocarcinoma using Kaplan-Meier and Cox regression analyses. Results: In the colorectal cancer cohort, severe postoperative complications (Clavien-Dindo III-V), higher lymph node ratio, tumor deposits, and modified Glasgow Prognostic Score 2 were independently associated with worse overall survival, while TNM stage, reduced peritumoral lymphocytic response, and tumor deposits predicted disease-free survival. In contrast, rectal adenocarcinoma demonstrated a distinct prognostic pattern: perineural invasion was associated with poorer overall survival in the exploratory rectal cancer subgroup analysis (hazard ratio (HR) = 25.125; P = 0.003), whereas platelet-to-lymphocyte ratio retained statistical significance with a modest effect size. Other systemic inflammatory and pathological parameters showed limited impact. Conclusions: Colon and rectal cancers exhibit divergent prognostic architectures. Combined analyses may reduce risk stratification accuracy and obscure the true value of inflammatory biomarkers, supporting the development of tumor site-specific prognostic models in colorectal oncology.