Beyond the tumor region: Peritumoral radiomics enhances prognostic accuracy in locally advanced rectal cancer.

Background: The peritumoral region possesses attributes that promote cancer growth and progression. However, the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.

Objective: To investigate the prognostic value and importance of peritumoral radiomics in locally advanced rectal cancer (LARC).

Methods: This retrospective study included 409 patients with biopsy-confirmed LARC treated with neoadjuvant chemoradiotherapy and surgically. Patients were divided into training (n = 273) and validation (n = 136) sets. Based on intratumoral and peritumoral radiomic features extracted from pretreatment axial high-resolution small-field-of-view T2-weighted images, multivariate Cox models for progression-free survival (PFS) prediction were developed with or without clinicoradiological features and evaluated with Harrell's concordance index (C-index), calibration curve, and decision curve analyses. Risk stratification, Kaplan-Meier analysis, and permutation feature importance analysis were performed.

Results: The comprehensive integrated clinical-radiological-omics model (ModelICRO) integrating seven peritumoral, three intratumoral, and four clinicoradiological features achieved the highest C-indices (0.836 and 0.801 in the training and validation sets, respectively). This model showed robust calibration and better clinical net benefits, effectively distinguished high-risk from low-risk patients (PFS: 97.2% vs 67.6% and 95.4% vs 64.8% in the training and validation sets, respectively; both P < 0.001). Three most influential predictors in the comprehensive ModelICRO were, in order, a peritumoral, an intratumoral, and a clinicoradiological feature. Notably, the peritumoral model outperformed the intratumoral model (C-index: 0.754 vs 0.670; P = 0.015); peritumoral features significantly enhanced the performance of models based on clinicoradiological or intratumoral features or their combinations.

Conclusions: Peritumoral radiomics holds greater prognostic value than intratumoral radiomics for predicting PFS in LARC. The comprehensive model may serve as a reliable tool for better stratification and management postoperatively.