Necrosis score as a prognostic factor in stage I-III colorectal cancer: a retrospective multicenter study

Background: Tumor necrosis results from failure to meet the requirement for rapid proliferation of tumor, related to unfavorable prognosis in colorectal cancer (CRC). However, previous studies used traditional microscopes to evaluate necrosis on slides, lacking a simultaneous phase and panoramic view for assessment. Therefore, we proposed a whole-slide images (WSIs)-based method to develop a necrosis score and validated its prognostic value in multicenter cohorts.

Methods: Necrosis score was defined as the proportion of necrosis in the tumor area, semi-quantitatively classified into 3-level score groups by the cut-off of 10% and 30% on HE-stained WSIs. 768 patients from two centers were enrolled in this study, divided into a discovery (N = 445) and a validation (N = 323) cohort. The prognostic value of necrosis score was evaluated by Kaplan-Meier curves and the Cox model.

Result: Necrosis score was associated with overall survival, with hazard ratio for high vs. low in discovery and validation cohorts being 2.62 (95% confidence interval 1.59-4.32) and 2.51 (1.39-4.52), respectively. The 3-year disease free survival rates of necrosis-low, middle, and high were 83.6%, 80.2%, and 59.8% in discovery cohort, and 86.5%, 84.2%, and 66.5% in validation cohort. In necrosis middle plus high subgroup, there was a trend but no significant difference in overall survival between surgery alone and adjuvant chemotherapy group in stage II CRC (P = .075).

Conclusion: As a stable prognostic factor, high-level necrosis evaluated by the proposed method on WSIs was associated with unfavorable outcomes. Additionally, adjuvant chemotherapy provide survival benefits for patients with high necrosis in stage II CRC.