Neoadjuvant Chemoradiotherapy vs. Neoadjuvant Chemotherapy for the Treatment of Esophageal Squamous Cell Carcinoma: A Stabilized Inverse Probability of Treatment Weighting Analysis

Abstract

<h3>Purpose/Objective(s)</h3> To compare long-term survival and safety of neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal squamous cell carcinoma (ESCC). <h3>Materials/Methods</h3> In 2012ཞ2020, patients diagnosed with ESCC were documented in the National Cancer Center database. as follows: 1) 18-75 years old; 2) histologically proven as stage T1-2N+M0 or T3-4N0-3M0; 3) histologic subtype was ESCC; 4) R0 resection; 5) radiotherapy dose ≥ 40Gy for primary tumor and metastatic lymph nodes. Stabilized inverse probability of treatment weighting (sIPTW) were used to minimize bias due to potential confounding factors, including sex, age, tumor location, tumor length, TNM clinical stage. The outcome included overall survival (OS), disease-free survival (DFS), pathological complete responses (pCR), and perioperative mortality and morbidity. <h3>Results</h3> A total of 419 patients (male,8 7.1%; mean age, 59.7 years) were enrolled to the nCRT group (n=158) or the nCT group (n=261). median follow-up time was 26 (7ཞ113) months in the nCRT group and 24 (7ཞ101) months in the nCT group, respectively. The chemotherapy regimen of nCT group was paclitaxel combined with platinum every 21 days with a median cycle of 3 (1ཞ4). In nCRT group, paclitaxel and platinum was performed weekly with a median of 3 cycles. The median radiotherapy dose for primary tumor and metastatic lymph nodes of 45Gy (40ཞ50.4Gy), 1.8ཞ2.14Gy/fraction, was delivered by intensity-modulated radiotherapy (IMRT) or volumetric intensity modulated arc therapy (VMAT). nCRT significantly improved the pCR rate as compared to nCT group (28.5% vs 9.2%, <i>P</i><0.001). The 1, 3 and 5-year OS in the nCRT and nCT group were 96.2% vs 98.1%, 78.4% vs 70.3% and 67.9% vs 53.3%, respectively (<i>P</i> =0.140). The incidence of anastomotic leak was in 13 of 158 patients (8.2%) in the nCRT group and 4 of 261 patients (1.5%) in the nCT group (<i>P</i> The total postoperative complications rate was 10.1% in the nCRT group (16 of 158) and 7.7% in the nCT group (20 of 261). After sIPTW, the clinical and demographic characteristics of the two groups were well balanced. The nCRT group was associated with a better OS than the nCT group (96.7% vs 97.6% at 1 year; 81.0% vs 69.2% at 3 years and 72.6% vs 48.2% 5 years, <i>P</i>=0.04). <h3>Conclusion</h3> Compared to nCT, paclitaxel and platinum-based nCRT using IMRT or VMAT technique improved OS in ESCC patients. Prospective head-to-head comparison and novel strategies with advanced drug therapy and radiotherapy technique to improve the outcomes in resectable ESCC are warranted.