Prognostic value of tumor-stroma ratio in a screened stage II colon cancer population: intratumoral site-specific assessment and tumor budding synergy.

The tumor-stroma ratio (TSR) has shown prognostic value in various cancers, including colon cancer. This retrospective, multicenter cohort study aimed to investigate the prognostic value of TSR in a screened stage II colon cancer population, both independently and in combination with tumor budding. The cohort included 497 patients who underwent surgical resection for stage II colon cancer. TSR was determined based on the procedures proposed by van Pelt et al., and tumor budding was evaluated according to the guidelines from the International Tumor Budding Consensus Conference (ITBCC). Our findings demonstrate that patients with tumors categorized as having a high proportion of stroma (> 50% stroma area) had a shorter 5-year time to recurrence (TTR) (HR = 1.95, p = 0.05), recurrence-free survival (RFS) (HR = 1.63, p = 0.02), and overall survival (OS) (HR = 1.05, p = 0.07) compared to patients with tumors categorized as having a low proportion of stroma (≤ 50% stroma area). The prognostic effect was specific to TSR determination at the deepest invasive front of the tumor and lost significance as the examination area expanded. Combining TSR and tumor budding further improved prognostic stratification. Tumors with high stromal content and high-grade budding exhibited a significantly more aggressive risk profile and poorer 5-year survival outcomes compared to patients with stroma-low and budding-low tumors (TTR; HR 4.47 p < 0.01, RFS; HR 2.71 p < 0.01, and OS; HR 2.20 p = 0.01). The study highlights the importance of standardized procedures for TSR assessment and suggests that evaluating both TSR and tumor budding could improve prognostic accuracy and aid in clinical decision-making.