The Roles Of Neo-/Adjuvant Treatment And Surgery Alone For Node-negative Esophageal Cancer: A SEER-based Propensity Matching Analysis

ObjectiveEsophageal cancer is a common malignant tumor and the sixth leading cause of cancer-related deaths.Neoadjuvant treatment followed by surgery has become the preferred approach for locally advanced and/or node-positive esophageal cancer(EC)with significantly improved survival outcomes.However,the optimal treatment procedure for early stages esophageal cancer is still in controversial.The purpose of this study was to compare the effects of neoadjuvant therapy,adjuvant therapy,and surgery alone on the prognosis of patients with lymph node-negative esophageal cancer.Basing on the available data from Surveillance,Epidemiology,and End Results(SEER)database,the most effective treatment for lymph node-negative esophageal cancer was initially investigated,which provided scientific basis and new ideas for the application of neo-/adjuvant therapy in early stages esophageal cancer.MethodsWe queried the SEER database basing on the National Cancer Institute(NCI)for patients who diagnosed as esophageal cancer from 2004 to 2016,and 64625 patients with available demographics and survival outcomes were included in this study.Potential confounders included patient sex,age at diagnosis,race,primary tumor site,tumor length,tumor histology,histologic grade,radiation sequence to surgery,chemotherapy used or not,tumor-node-metastasis stage(TNM)stage,examined lymph node(ELN)and survival-related information.According to the corresponding inclusion and exclusion criteria,clinically staged node-negative(cN-)esophageal cancer treated with neoadjuvant chemoradiotherapy plus surgery(CRT + S)and surgery alone(SA),pathological staged node-negative(pN-)esophageal cancer treated with SA and adjuvant radiotherapy(S + RT),and CRT + S versus S + RT were compared to evaluate the effect of related treatments on the prognosis of patients with early stages esophageal cancer.The endpoints of this study included overall survival(OS)and cancer-specific survival(CSS).Propensity score matching(PSM)was used to eliminate baseline demographic differences and achieve better patient group homogeneity by logistic regression.Kaplan–Meier survival analysis and the log-rank test were used for the OS and CSS distributions.Multivariable analysis was performed using a Cox proportional hazards regression model.Significant values were defined as those with a P < 0.05.ResultsPart 1: Neoadjuvant CRT plus surgery Vs SA for cN-esophageal cancer.A total of 1587 patients were retrospectively identified,of whom 49.8%(n = 791) received nCRT and 80.2%(n = 1273) were truly node-negative(pN-)diseases.After matching,nCRT was associated with improved 5-yr OS for localized truly node-negative(pT3-4N0)(59.6% vs 37.7%;P <.001)and falsely node-negative disease(60.5% vs 40.7%;P =.002).Cox multivariate regression analysis revealed that the addition of nCRT for pN-patients with tumor length ? 3cm,pT1-2N0 and localized disease were independent risk factors for survival than SA(P <.01).Part 2: Adjuvant RT Vs SA for pN-esophageal cancer.There were 3197 patients selected,of whom 321(10.0%)received postoperative radiation.On subgroup analysis,postop RT was associated with improved 5-yr OS(34.8% vs 27.7%;P =.008)for pT3-4N0 disease.The Cox multivariate regression analysis revealed that the addition of adjuvant RT for pT3-4N0 diseases with tumor length ? 3 cm,adenocarcinoma and ELN < 12,was a powerful prognostic factor for improved OS(P <.01).Part 3: Neoadjuvant CRT plus surgery Vs adjuvant RT for node-negative esophageal cancer.There were 821 patients selected,of whom 588(71.6%)received neoadjuvant CRT and 233(28.4%)received adjuvant RT.Neoadjuvant CRT was associated with a significantly benefit in 5-yr survival outcomes compared with adjuvant RT(P <.01),but the survival differences disappeared for matched patients.The Cox multivariate regression analysis revealed that the addition of nCRT for nodenegative disease was not a prognostic factor than adjuvant approach.ConclusionIn this population-based study,surgery alone can be a preferred treatment for pT1-2N0 disease.However,the addition of postoperative radiation for pT3-4N0 diseases after upfront esophagectomy was associated with improved overall survival in highrisk patients.Neoadjuvant chemoradiotherapy or adjuvant radiotherapy significantly improved the prognosis of patients with pT3-4N0 disease compared with surgery alone,but no survival difference was observed between the two treatment procedures.This finding may have significant implications on the use of neo-/adjuvant therapy in patients with lymph node-negative disease.