Development and validation of a post-chemoradiotherapy prognostic model in patients with locally advanced rectal cancer who underwent radical surgery after neoadjuvant chemoradiotherapy: a retrospective, multicenter, cohort study

Introduction: The American Joint Committee on Cancer (AJCC) neoadjuvant pathological TNM (ypTNM) staging system is the standard for assessing the risk and prognosis for locally advanced rectal cancer (LARC) patients receiving neoadjuvant chemoradiotherapy (nCRT). Tumor regression grading (TRG) is also recommended by the AJCC to evaluate the pathological response to nCRT for LARC. Yet, the prognostic value of combining the ypTNM staging system with TRG has not been fully defined. Methods: This multicenter, retrospective cohort study included training and external validation cohorts of LARC patients with nCRT from four Chinese hospitals: XX. Overall survival was assessed by Kaplan-Meier analysis, log-rank tests and the Cox regression model to ascertain independent prognostic factors. A nomogram of the TRG-ypTNM prognostic model was established. The evaluation of this model’s performance was assessed through Harrell’s concordance index (c-index), time-dependent Receiver Operating Characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Results: A total of 1046 LARC patients were included in the training cohort and 354 patients in the validation cohort. TRG and ypTNM were recognized as independent prognostic factors in both the training and external validation cohorts. The novel TRG-ypTNM prognostic model showed better prognostic discrimination than the ypTNM staging system in both the training and validation cohorts. The calibration curves and DCA showed satisfactory accuracy and clinical utility of this novel model. Conclusions: TRG and ypTNM were recognized as independent prognostic factors for LARC patients receiving nCRT. The novel TRG-ypTNM prognostic model appears ideal for further stratifying the risk and prognosis for LARC patients undergoing nCRT.