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Integrating perioperative inflammation and pathological invasiveness to predict recurrence after curative colorectal cancer surgery: a multicenter cohort study
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DOI：10.3389/fonc.2026.1861588.png)
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Abstract
En 中文
BackgroundRecurrence risk after curative surgery for non-metastatic colorectal cancer (CRC) remains heterogeneous within the same TNM stage. Pathological invasiveness and perioperative systemic inflammation may provide complementary prognostic information; but their combined value and the role of early postoperative inflammatory dynamics remain insufficiently defined. We aimed to develop and externally validate a multicenter prognostic model integrating invasive pathological features with perioperative inflammatory biomarkers to improve recurrence-free survival (RFS) prediction.Patients and methodsWe retrospectively included 1; 260 patients with stage I-III colorectal adenocarcinoma who underwent curative-intent resection between January 2017 and March 2023. The development cohort comprised 1; 008 consecutive patients from Qilu Hospital of Shandong University; and the external validation cohort comprised 252 patients from three regional hospitals. Data extraction followed a prespecified case-report framework with harmonized definitions for pathology; perioperative laboratory timing; adjuvant treatment; surgical approach; MSI/MMR status; and follow-up. The final Cox model was evaluated against prespecified comparator models; with additional sensitivity analyses adjusting for adjuvant chemotherapy; surgical approach; and MSI status.ResultsThe reduced final pathology-inflammation model incorporated eight predictors: histological differentiation; pN stage; extramural venous invasion (EMVI); tumor budding (BD); tumor deposits (TD); preoperative CEA; preoperative systemic immune-inflammation index (preSII); and postoperative day-1 C-reactive protein-to-albumin ratio (postCAR). The final model used 9 effective parameters and 437 recurrence events in the development cohort; corresponding to an events-per-variable ratio of 48.6. Its apparent Harrell C-index was 0.786 in the development cohort and 0.793 in the external validation cohort; bootstrap-based internal validation showed minimal optimism (mean optimism 0.003; optimism-corrected C-index 0.783). Adding adjuvant chemotherapy; surgical approach; and MSI status did not materially change discrimination in either cohort. The development-derived cutoff retained clinically meaningful separation in the external validation cohort; with 3-year sensitivity of 78.0% and specificity of 72.5%.ConclusionsIn this multicenter study; a reduced pathology-inflammation model improved postoperative recurrence prediction beyond conventional clinicopathologic assessment in stage I-III CRC and remained stable after adjustment for newly incorporated treatment; surgical approach; and MSI/MMR information. Because postoperative inflammatory markers may partly reflect operative and early postoperative factors; and because the study remains retrospective; the model should be interpreted as a risk-stratification aid requiring prospective validation before routine clinical implementation.
Keywords:
colorectal cancer
external validation
prognostic model
recurrence-free survival
systemic inflammation
tumor-host interaction
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