Risk Factors And Prediction Model Of Postoperative Recurrence Of PT1-3N0M0 Esophageal Squamous Cell Carcinoma

Objective: Esophageal cancer is the sixth leading cause of cancer death in the world.In China,esophageal squamous cell carcinoma(ESCC)is the main histological subtype.At present,combined treatment mainly by surgery is the main treatment method for patients with ESCC,but the overall survival prospects are not optimistic.The postoperative recurrence rate is still high and the prognosis is still not ideal even in patients with negative pathological examination of lymph node(p N0)after surgery.Accurate judgment of patients’ tumor recurrence is the premise of accurate treatment,but also the key to improve the survival rate and quality of life of patients.At present,there is still a lack of reliable tumor recurrence prediction indicators for these patients.Our aim,therefore,was to explore independent risk factors for tumor recurrence in patients with p N0 esophageal squamous cell carcinoma after surgery and to establish a simple,practical,and effective prediction model to screen out high-risk patients and allow us to personalize and target therapy for these patients to improve long-term survival.Methods:We retrospectively analyzed the clinical and pathological data of patients with pT1-3N0M0 esophageal squamous cell carcinoma who underwent radical resection at the Department of Thoracic Surgery,the Affiliated Hospital of Qingdao University from January 2014 to December 2019.Cox regression analysis was used to determine the independent risk factors of tumor recurrence,and a nomogram prediction model was established to predict tumor recurrence,and the model was evaluated by concordance index(C-index),receiver operating characteristic curves(ROC curves)and calibration curve.bootstrap resampling and k-fold cross validation were used to further validate the model internally,and Td-ROC,NRI,IDI and DCA were used to compare the predictive ability of the prediction model with the AJCC TNM staging,8th edition.The recurrence risk score was calculated according to the prediction model,and the patients were divided into high-risk group and low-risk group.Results: A total of 270 patients were included in this study.The median follow-up duration was 45 months.89 patients(33.0%)had developed a locoregional or/and distant recurrence at the time of review.Univariate analyses revealed that pT-category(P<0.001),tumor length(P<0.001),lymphovascular invasion(P<0.001),perineural invasion(P<0.001),differentiation(P=0.005),BMI(P=0.02),alcohol use disorder(P=0.026),sex(P=0.078),prognostic nutritional index(PNI)(P=0.083),ELN(P=0.096)were identified as significant prognostic factors for recurrence(P<0.1).Multivariate Cox regression analysis showed that pT-category,differentiation,perineural invasion,number of lymph nodes dissected and prognostic nutritional index were independent prognostic factors for postoperative recurrence of ESCC.Therefore,we used the results of multivariate Cox regression analysis to construct a Nomogram to predict postoperative recurrence-free survival(RFS)in patients with pT1-3N0M0 ESCC,including pT stage,degree of differentiation,nerve invasion,number of lymph nodes dissected,and prognostic nutritional index.The C-index of the prediction model was 0.745(95%CI,0.794-0.696),and the discrimination was good.The calibration curve also showed favorable consistency between the predicted recurrence rate and the actual recurrence rate.The C-index of bootstrap resampling cohort was 0.725 for internal validation of the model.Td-ROC,NRI,and IDI showed a better predictive ability than the AJCC 8th TNM staging system.The DCA curve showed that the prediction model had better clinical utility than TNM staging.Based on the total recurrence risk score calculated by the model,patients could be divided into low-risk group and high-risk group.The recurrence rate of patients in the low-risk group was significantly lower than that in the high-risk group(P < 0.001).Conclusion: pT stage,differentiation,perineural invasion,number of dissected lymph nodes and prognostic nutritional index are independent prognostic factors for postoperative recurrence of ESCC.The prediction model based on these pathological features and peripheral blood indicators is helpful to accurately predict tumor recurrence in patients with pT1-3N0M0 ESCC after surgery.There may be a clear survival benefit from stratified patient management.