Overstaging of the mesorectal fascia following neoadjuvant therapy and its impact on therapeutic management: a single-center retrospective cohort study of 506 mesorectal fascia positive patients.

Abstract

Background: Accurate assessment of mesorectal fascia (MRF) involvement status after neoadjuvant therapy (NAT) is critical for guiding post-NAT treatment. However, the discordance between magnetic resonance imaging (MRI)-based evaluations and histopathological results may drive overtreatment and complicate organ-preservation strategies. This study aimed to evaluate the association between post-NAT MRF involvement and pathological circumferential resection margin (CRM) positivity.

Methods: This retrospective cohort study included treatment-naïve rectal cancer patients with MRI-confirmed MRF involvement between January 2014 and January 2024. All patients underwent MRI restaging after the NAT. The diagnostic performance, including sensitivity and specificity, of MRI-assessed MRF status was assessed to determine its efficacy in predicting pathological CRM positivity. Logistic regression and mixed-effects models were used to quantify the association between MRF status and CRM positivity. Cox regression analysis was used to assess the effect of MRF positivity on survival outcomes.

Results: Among 506 enrolled patients, restaging MRI showed persistent MRF involvement in 50.2% (254/506). The CRM-positive rate was 10.2% in the MRF-positive group, compared to 1.6% in the MRF-negative group. Concordance between MRI and pathological assessment was poor (sensitivity: 0.867, specificity: 0.521, Kappa: 0.086). Nevertheless, MRF positivity independently predicted CRM positivity [odds ratio (OR): 6.228, 95% confidence interval (CI): 2.349-21.507, P<0.001]. In non-metastatic (M0) patients, MRF positivity correlated with worse overall survival [hazard ratio (HR): 2.300, 95% CI: 1.067-4.957, P=0.03]. However, no significant association was observed in metastatic (M1) patients (HR: 1.614, 95% CI: 0.859-3.031, P=0.14). For patients with post-NAT MRF-positive, integrating RAS status improved postoperative survival prediction accuracy [area under the curve (AUC): 1-year: 0.74 vs. 0.59; 3-year: 0.66 vs. 0.58; 5-year: 0.75 vs. 0.63].

Conclusions: MRI assessment of MRF involvement showed limited concordance with pathological CRM status after NAT. Integration of MRF status and RAS status refines prognostic stratification in non-metastatic MRF-positive rectal cancer, guiding subsequent treatment decisions.