Comparative Analysis of Clinical Outcomes Between Neoadjuvant Chemoimmunotherapy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Retrospective Study

Comparative Analysis of Clinical Outcomes Between Neoadjuvant Chemoimmunotherapy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparative Analysis of Clinical Outcomes Between Neoadjuvant Chemoimmunotherapy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Retrospective Study Xue Yan, Ying Peng, Peng Mo, Liuyu Li, Weijing Jiang, Wenzhen Zhang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5797124/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Patients with locally advanced esophageal squamous-cell carcinoma (LA-ESCC) generally experience poor prognosis after surgery. Neoadjuvant therapy has shown potential to improve survival outcomes. This study aimed to compare the long-term efficacy and safety of neoadjuvant chemoimmunotherapy (nCIT) versus neoadjuvant chemoradiotherapy (nCRT) in patients with LA-ESCC. Methods This multicenter study included patients with LA-ESCC treated at three hospitals in China between November 2015 and January 2024. Patients underwent either nCIT or nCRT followed by surgical resection. The primary endpoint was the 3-year overall survival (OS) rate. Secondary outcomes included objective response rate (ORR), pathologic complete response (pCR) rate, major pathologic response, disease-free survival (DFS), OS, and treatment-related adverse events. Propensity score matching was employed to adjust for baseline differences. Results A total of 225 LA-ESCC patients were included in this study, with 87 patients receiving nCRT and 138 patients receiving nCIT. After propensity score matching adjustment, each group have 87 patients included. The nCRT group demonstrated significantly superior outcomes to nCIT group in terms of ORR (85.06% vs. 45.98%, p < 0.001), T stage down rate (78.16% vs. 58.62%, p = 0.006), N stage down rate (85.06% vs. 45.98%, p < 0.001) and pCR rate (37.90% vs 14.90%, p < 0.001). The median follow-up duration was 44.5 months for the nCIT group and 35.1 months for the nCRT group. The nCIT group exhibited better 3-year OS (75.90% vs 55.60%, P < 0.05) andDFS (66.40% vs. 47.30%, P = 0.009) compared to the nCRT group. Subgroup analysis indicated that LA-ESCC patient with N + or non cT4 stage who received neoadjuvant chemoradiotherapy followed by esophagectomy had better OS and DFS. Univariate and multivariate Cox regression analyses identified clinical N stage as an independent prognostic factor for both OS and disease-free survival across both cohorts. Conclusion Neoadjuvant chemoimmunotherapy followed by esophagectomy is a promising treatment strategy for locally advanced resectable esophageal squamous cell carcinoma. nCRT may provide greater benefits in patients with N + or non-cT4 stage disease. Locally advanced resectable esophageal squamous cell carcinoma Neoadjuvant chemoradiotherapy Immunotherapy Survival Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Esophageal cancer is one of the most common cancers globally, ranking seventh in incidence and sixth in mortality among all cancers [ 1 ] . Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in Asia [ 2 ] , accounting for over 84% of all esophageal cancer cases [ 3 ] . In the early stages of esophageal cancer, patients often remain asymptomatic, leading to the majority being diagnosed at a locally advanced stage. Currently, esophagectomy is the primary treatment for patients with resectable locally advanced-ESCC (LA-ESCC). However, surgery alone often results in high recurrence rates and poor survival outcomes [ 3 ] . There is growing evidence that neoadjuvant therapy can improve survival in patients with LA-ESCC. The CROSS clinical trial demonstrated that neoadjuvant chemoradiotherapy (nCRT) followed by surgery significantly improved overall survival (OS) in patients with LA-ESCC compared to surgery alone [ 4 – 5 ] . Similarly, the JCOG9907 clinical study compared the efficacy and safety of neoadjuvant chemotherapy (nCT) to adjuvant chemotherapy in treating LA-ESCC, finding that nCT significantly enhanced OS with an acceptable safety profile [ 6 ] . Immune checkpoint inhibitors (ICIs), such as PD-1 and PD-L1 inhibitors, have demonstrated efficacy in treating advanced ESCC and other cancers [ 7 – 9 ] . Additionally, several preclinical studies have highlighted the synergistic effects of combining ICIs with chemotherapy or radiotherapy [ 10 – 11 ] . Despite these advancements, there is still a limited number of studies comparing the efficacy of nCRT versus neoadjuvant chemotherapy combined with immunotherapy (nCIT) in resectable LA-ESCC [ 12 – 14 ] . Therefore, this study aimed to compare the treatment responses and long-term survival outcomes of patients with resectable LA-ESCC who received nCRT versus nCIT followed by esophagectomy. Methods Methods and patients This study included patients with LA-ESCC who received either nCIT or nCRT, followed by esophagectomy, at three hospitals (the 900th Hospital, Fujian Cancer Hospital, and Quanzhou Guangqian Hospital) in China between November 2015 and January 2024. The inclusion criteria were: (1) age > 18 years old; (2) ECOG score of 0 to 1; (3) thoracic ESCC with clinical stage from T2-4N0M0 or TanyN + M0 based on AJCC 8th; (4) completed neoadjuvant therapy followed by surgery; (5) postoperative pathologic diagnosis of squamous cell carcinoma; (6) No history of any antitumor therapy, such as targeted therapy or immunotherapy; and (7) Availability of complete clinical data and survival or follow-up information. The exclusion criteria were: (1) postoperative pathological diagnosis of non-squamous cell carcinoma; (2) incomplete neoadjuvant therapy or failure to undergo transthoracic esophagectomy following neoadjuvant therapy; (3) receipt of radical radiation therapy; (4) missing clinical data; and (5) presence of other concurrent malignant tumors. The study was approved by institutional ethics board of the 900th Hospital of the Joint Logistics Team (No. 2024-032) and individual consent for this retrospective analysis was waived. Treatments Patients in the nCRT group received concurrent chemoradiotherapy. The radiotherapy regimen consisted of 40–50 Gy, delivered in 20–25 fractions, with 5 fractions per week. Concurrent chemotherapy included two options: (1) paclitaxel (45–60 mg/m²) combined with cisplatin (20–25 mg/m²) weekly, or (2) cisplatin (30 mg/m²) combined with capecitabine (800 mg/m²) weekly. Patients in the nCIT group received immunotherapy in combination with concurrent TP chemotherapy. Immunotherapy agents included toripalimab (240 mg every 3 weeks), camrelizumab (200 mg every 3 weeks), pembrolizumab (200 mg every 3 weeks), sintilimab (200 mg every 3 weeks), or tislelizumab (200 mg every 3 weeks). The TP chemotherapy regimen included albumin-bound paclitaxel (175 mg/m²) or docetaxel (70 mg/m²) combined with cisplatin (75 mg/m²) or nedaplatin (75 mg/m²), administered every 3 weeks. After completing neoadjuvant therapy, all patients in both the nCIT and nCRT groups underwent minimally invasive McKeown esophagectomy. Endpoints and assessments The primary endpoint was 3-year OS rate. Second endpoints included pCR, MPR, ORR, DFS and TRAEs. AEs were assessed according to the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0). MPR was defined as ≤ 10% residual viable tumor cells in the resected tumor bed, evaluated by H&E-stained slides. [ 15 ] pCR was defined as the absence of viable tumor cells in both the primary tumor site and resected lymph nodes. [ 16 ] OS was defined as the time from treatment to death from any cause, while DFS referred to the time from treatment to disease progression, recurrence at any site, or death from any cause. [ 17 ] Statistical analysis Categorical variables were compared between the two groups using the chi-square test or Fisher’s exact test, and numerical variables were compared using the independent t-test. PSM was applied to minimize baseline differences between the nCIT and nCRT groups, adjusting for measured confounders. [ 18 ] . Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors for OS and DFS in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Kaplan-Meier survival curves and log-rank tests were used to compare OS and DFS between the two groups. Statistical analyses were performed using R software (version 4.4.1) and SPSS (version 27.0), with a significance threshold set at a p-value < 0.05. Results Patient clinical characteristics A total of 225 patients were included in this study, including 138 patients who received nCIT and 87 patients who received conventional nCRT as shown in Fig. 1 . The median follow-up duration was 44.5 months for the nCIT group and 35.1 months for the nCRT group. Baseline characteristics were presented in Table 1 . The two groups differed significantly in age, smoking status, tumor location, and clinical T stage, but there were no significant differences in sex, alcohol history, clinical N stage, or clinical stage. To address baseline imbalances, a 1:1 case-control analysis was performed using PSM. After PSM adjustment, baseline characteristics were well-balanced between the two treatment groups, as shown in Table 2 . Each group consisted of 87 patients following matching. Table 1 Baseline characteristics Baseline feature, n (%) nCRT (n = 87) nCIT (n = 138) p Sex 0.927 male 70 (80.5) 113 (81.9) female 17 (19.5) 25 (18.1) Age (years old) 0.047 ≤ 61 53 (60.9) 64 (46.4) >61 34 (39.1) 74 (53.6) Smoking 0.003 no 65 (74.7) 75 (54.3) yes 22 (25.3) 63 (45.7) Drinking 0.153 no 70 (80.5) 98 (71.0) yes 17 (19.5) 40 (29.0) Tumor site 0.031 upper throacic segment 12 (13.8) 16 (11.6) middle thoracic segment 64 (73.6) 84 (60.9) lower thoracic segment 11 (12.6) 38 (27.5) Clinical T stage 0.008 T1 0 (0.0) 2 (1.4) T2 3 (3.4) 20 (14.5) T3 79 (90.8) 100 (72.5) T4 5 (5.7) 16 (11.6) Clinical N stage 0.131 N0 28 (32.2) 32 (23.2) N1 31 (35.6) 40 (29.0) N2 25 (28.7) 57 (41.3) N3 3 (3.4) 9 (6.5) C linical stage 0.174 I 0 (0.0) 1 (0.7) Ⅱ 30 (34.5) 33 (23.9) Ⅲ 49 (56.3) 81 (58.7) Ⅳ 8 (9.2) 23 (16.7) nCIT: Neoadjuvant chemotherapy plus immunotherapy; nCRT: Neoadjuvant chemoradiotherapy. Table 2 Baseline characteristics after PSM Baseline feature, n (%) nCRT (n = 87) nCIT (n = 87) p Sex 0.852 male 70 (80.5) 68 (78.2) female 17 (19.5) 19 (21.8) Age (years old) 0.285 ≤ 61 53 (60.9) 45 (51.7) >61 34 (39.1) 42 (48.3) Smoking 0.318 no 65 (74.7) 58 (66.7) yes 22 (25.3) 29 (33.3) Drinking 0.582 no 70 (80.5) 66 (75.9) yes 17 (19.5) 21 (24.1) Tumor site 0.465 upper thoracic segment 12 (13.8) 11 (12.6) middle thoracic segment 64 (73.6) 59 (67.8) lower thoracic segment 11 (12.6) 17 (19.5) Clinical T stage 0.953 T2 3 (3.4) 3 (3.4) T3 79 (90.8) 78 (89.7) T4 5 (5.7) 6 (6.9) Clinical N stage 0.875 N0 28 (32.2) 25 (28.7) N1 31 (35.6) 29 (33.3) N2 25 (28.7) 30 (34.5) N3 3 (3.4) 3 (3.4) Clinical stage 0.933 Ⅱ 30 (34.5) 28 (32.2) Ⅲ 49 (56.3) 50 (57.5) Ⅳ 8 (9.2) 9 (10.3) nCIT: Neoadjuvant chemotherapy plus immunotherapy; nCRT: Neoadjuvant chemoradiotherapy; PSM: Propensity score matching. Efficacy results As presented in Table 3 , the nCRT group showed significantly better outcomes than the nCIT group in terms of ORR (85.06% vs. 45.98%, p < 0.001), postoperative T stage (78.16% vs. 58.62%, p = 0.006) N stage descending rate (85.06% vs. 45.98%, p < 0.001) as well as the pCR rate (37.9% vs 14.9%, p < 0.001). Table 3 Treatment responses of the two groups n (%) nCRT (n = 87) nCIT (n = 87) P PR/CR <0.001 yes 74(85.1) 40(46.0) no 13(14.9) 47(54.0) pCR <0.001 yes 33(37.9) 13(14.9) no 54(62.1) 74(85.1) MPR 0.034 yes 51(58.6) 37(42.5) no 36(41.4) 50(57.5) Postoperative T stage descending 0.006 yes 68(78.2) 51(58.6) no 19(21.8) 36(41.4) Postoperative N stage descending <0.001 yes 74(85.1) 40(46.0) no 13(14.9) 47(54.0) nCIT: Neoadjuvant chemotherapy plus immunotherapy; nCRT: Neoadjuvant chemoradiotherapy; PSM: Propensity score matching; ORR: Objective response rate; pCR: Pathologic complete response; MPR: major pathological response. The 1-, 2-, and 3-year DFS and OS rates for the nCRT and nCIT are shown in Table 4, Additionally, nCIT group had longer OS and DFS compared to the nCRT group (p < 0.05) (Fig. 2 ). Subgroup analysis revealed that patients with LA-ESCC and clinical N + or non-cT4 stage in the nCRT group had significantly longer mOS and mDFS (Fig. 3 ). However, for patients with LA-ESCC and clinical N- or cT4 stage, there were no significant differences in OS and DFS between nCIT group and nCRT group (Fig. 4 ). In addition, among patients with pCR, there was no significant difference in OS and DFS between the two treatment groups (Fig. 4 ). Table 4. Long-term survival outcomes of the two groups nCIT nCRT 1-year DFS 91.72% 76.55% 2-year DFS 76.73% 55.09% 3-year DFS 66.35% 47.32% 1-year OS 96.43% 88.27% 2-year OS 82.49% 68.03% 3-year OS 75.89% 55.57% nCIT: Neoadjuvant chemotherapy plus immunotherapy; nCRT: Neoadjuvant chemoradiotherapy; DFS: Disease-free survival; OS: Overall survival. Univariate and multivariate Cox regression analyses identified clinical N stage as an independent prognostic factor for OS and DFS. Specifically, for OS, the hazards ratios (HR) for N1, N2, and N3 were 2.27 (95% CI = 1.04–4.94, p = 0.04), 2.65 (95% CI = 1.23–5.74, p = 0.013), and 10.79 (95% CI = 3.22–36.17, p < 0.001), respectively, as shown in Fig. 5 . For DFS, the HR for N2 was 1.93 (95% CI = 1.04–3.56, p = 0.037), and for N3, the HR was 3.30 (95% CI = 1.09–9.98, p = 0.035) as shown in Fig. 6 . These findings suggest that LA-ESCC patients with clinical N2 or N3 stage are at higher risk for tumor progression and have poorer prognosis. Safety results AEs in this study were defined as complications occurring from the initiation of neoadjuvant therapy through one week after surgery completion. As shown in Table 5 , after PSM, no statistically significant differences were observed in the incidence of myelosuppression of Grade ≥ 3 (16.09% vs. 17.24%), liver dysfunction of Grade ≥ 3 (2.30% vs. 0%), vomiting of Grade ≥ 3 (6.70% vs. 2.30%), pneumonia (36.78% vs. 24.14%), or esophageal fistula (1.15% vs. 3.45%) between the nCRT and nCIT groups (p > 0.05). Table 5 Treatment related adverse events post neoadjuvant therapy TRAEs n (%) nCRT (n = 87) nCIT (n = 87) P Myelosuppression 0.839 Grade 1/2 73(83.9) 72(82.8) Grade ≥ 3 14(16.1) 15(17.2) Liver dysfunction 0.497 Grade 1/2 85(97.7) 87(1) Grade ≥ 3 2(2.3) 0 Vomiting 0.278 Grade 1/2 81(93.1) 85(97.7) Grade ≥ 3 6(6.9) 2(2.3) Pneumonia 0.070 yes 32(36.8) 21(24.1) no 55(63.2) 66(75.9) Esophageal fistula 0.621 yes 1(1.1) 3(3.4) no 86(98.9) 84(96.6) nCIT: Neoadjuvant chemotherapy plus immunotherapy; nCRT: Neoadjuvant chemoradiotherapy. Discussion nCIT, as a novel neoadjuvant therapeutic approach, has been demonstrated to exhibit definitive efficacy in various solid tumors, such as non-small cell lung cancer and triple-negative breast cancer [ 19 , 20 ] . In the first reported multicenter clinical study, we observed that patients with LA-ESCC treated with nCIT followed by esophagectomy demonstrated better OS and DFS compared to those receiving nCRT followed by surgery. A retrospective study by Yu YK et al. which analyzed the efficacy of neoadjuvant therapy in 202 patients with LA-ESCC (81 receiving nCIT and 121 receiving nCRT), found that after adjustment for inverse probability of treatment weighting, the nCIT group had superior 3-year OS (91.70% vs. 79.80%; p = 0.032) and 3-year DFS (87.40% vs. 72.80%; p = 0.039) compared to the nCRT group, which was similar to the results of our study. However, contrasting findings have been reported in other single-center studies [ 21 ] . Zhao et al. reported that the nCRT group had significantly superior DFS and OS compared to the nCIT group (12-month DFS: 94.30% vs. 81.80%, p = 0.006; 12-month OS: 100.00% vs. 95.40%, p = 0.032) [ 22 ] . These mixed results underscore the need for further research to compare the efficacy of nCRT and nCIT in LA-ESCC. Our study’s multivariate Cox regression analysis identified clinical N stage as an independent prognostic factor for both DFS and OS ( p < 0.05). With data from multiple centers and long-term follow-up, our research provides a robust comparison of these two treatment modalities, highlighting the potential long-term benefits of tumor immunotherapy. Subgroup analysis revealed that patients with N-positive disease had significantly longer DFS and OS in the nCIT group ( p < 0.05), suggesting that nCIT may offer particular advantages for LA-ESCC patients with N-positive status. Patients with lymph node-positive status often have undetectable metastases in the bloodstream at the time of diagnosis [ 23 ] . Compared to the localized effects of radiotherapy, immunotherapy may reduce recurrence in this patient population through its systemic therapeutic effects. A retrospective study comparing the feasibility and safety of nCRT plus surgery versus nCIT plus surgery in 64 patients with resectable LA-ESCC found that the nCRT group had better pathological responses, with a pCR rate of 43.80% vs. 18.80% and a MPR rate of 71.90% vs. 34.40% compared to the nCIT group [ 24 ] . Similarly, our study showed that the nCRT group had a higher pCR rate (37.90% vs. 14.90%, p < 0.001). Furthermore, Another retrospective cohort study involving 44 patients (23 in the nCRT group and 21 in the nCIT group) found no significant difference in adverse event rates or post-surgery pathological remission rates between the two groups [ 25 ] , which contrasts with our findings in terms of pathological response, likely due to retrospective biases and small sample size. Previous study have shown that patients achieving pCR often experience prolonged DFS and OS [ 26 ] . However, A meta-analysis indicated that patients with early-stage triple-negative breast cancerwho achieved pathological complete response (defined as ypT0, ypN0 or ypT0/is ypN0) demonstrated improved survival rates [ 27 ] . The KEYNOTE-585 study also have shown that combining immunotherapy with chemotherapy increased the pCR rate by 10% compared to the chemotherapy-alone group, but neither EFS nor OS reached the predefined endpoints [ 28 ] . It is important to recognize that pCR does not always equate to optimal outcomes. Neoadjuvant therapies can cause adverse effects, such as cardiotoxicity, which may diminish patients’ quality of life. Additionally, even in cases where pCR is achieved, micrometastatic disease or minimal residual cancer may persist, potentially leading to recurrence or metastasis and, ultimately, treatment failure. Consequently, while pCR rates are valuable, greater emphasis should be placed on DFS and OS as comprehensive measures of therapeutic success. This study has several limitations. First, as a retrospective analysis, the results may still be subject to inherent biases despite the application of PSM to mitigate them. Additionally, the relatively small sample size limits the robustness of the findings, highlighting the need for larger studies. Furthermore, the follow-up period is limited, requiring longer follow-up to more accurately assess long-term survival outcomes. We plan to continue monitoring patient survival and update the findings in future studies. Conclusions Neoadjuvant chemoimmunotherapy followed by surgery is well tolerated and effective treatment option for locally advanced resectable esophageal squamous cell carcinoma, especially for patients with lymph node-positive disease. Declarations Conflict of Interest All authors declare no potential conflicts of interest or financial relationships related to the conduct of this study. Data Availability Statement The raw data from this study are not publicly available to protect patient privacy. For access to the research data, please contact the corresponding author. Author contributions Zhichao Fu, Xue Yan and Yongshi Shen concepted and designed the study; Data collection was done by Ying Peng and Peng Mo; formal analysis was done by Xue Yan, Ying Peng, Miaoyi Su, Liuyu Li, Weijing Jing, Wenzhen Zhang, Peng Mo, Yuanji Xu. 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Safety and Feasibility of Esophagectomy Following Combined Immunotherapy and Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score Matching Analysis[J]. Front Immunol. 2022;13:836338. Zhang H, Zhang Z, Yang L, et al. Perioperative outcomes of neoadjuvant immunotherapy plus chemotherapy and neoadjuvant chemoradiotherapy in the treatment of locally advanced esophageal squamous cell carcinoma: a retrospective comparative cohort study[J]. J Thorac Disease. 2023;15(3):1279–88. Wu T-T, Chirieac LR, Abraham SC, et al. Excellent Interobserver Agreement on Grading the Extent of Residual Carcinoma After Preoperative Chemoradiation in Esophageal and Esophagogastric Junction Carcinoma: A Reliable Predictor for Patient Outcome[J]. Am J Surg Pathol. 2007;31(1):58. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis[J]. Lancet (London England). 2014;384(9938):164–72. Shitara K, Rha SY, Wyrwicz LS, et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study[J]. Lancet Oncol. 2024;25(2):212–24. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5797124","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":400494605,"identity":"27e208bd-88ad-4f63-94a7-4021791c28f9","order_by":0,"name":"Xue Yan","email":"","orcid":"","institution":"Fuzong Clinical Medical College (900th Hospital), Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xue","middleName":"","lastName":"Yan","suffix":""},{"id":400494606,"identity":"a6ea81bd-798c-458c-a6e0-c130e1c0aef4","order_by":1,"name":"Ying Peng","email":"","orcid":"","institution":"Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Peng","suffix":""},{"id":400494608,"identity":"af7f6d8a-7475-4fd9-90d2-653a595fe587","order_by":2,"name":"Peng Mo","email":"","orcid":"","institution":"Fuzong Clinical Medical College (900th Hospital), Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Mo","suffix":""},{"id":400494610,"identity":"671dc2c8-e22d-4255-b9a0-e831b7edbc32","order_by":3,"name":"Liuyu Li","email":"","orcid":"","institution":"Fuzong Clinical Medical College (900th Hospital), Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Liuyu","middleName":"","lastName":"Li","suffix":""},{"id":400494612,"identity":"5be7abd8-5767-4ee9-8f09-3d9083cce22c","order_by":4,"name":"Weijing Jiang","email":"","orcid":"","institution":"Fuzong Clinical Medical College (900th Hospital), Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Weijing","middleName":"","lastName":"Jiang","suffix":""},{"id":400494613,"identity":"33bcb408-9ed0-4c13-b86f-f2e23e57229e","order_by":5,"name":"Wenzhen Zhang","email":"","orcid":"","institution":"Fuzong Clinical Medical College (900th Hospital), Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenzhen","middleName":"","lastName":"Zhang","suffix":""},{"id":400494614,"identity":"bafa5c91-f522-4762-8eea-a5ee723ab71e","order_by":6,"name":"Yuanji Xu","email":"","orcid":"","institution":"Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuanji","middleName":"","lastName":"Xu","suffix":""},{"id":400494615,"identity":"8cfb4ceb-c563-42f1-869e-4d6d24fd12cd","order_by":7,"name":"Miaoyi Su","email":"","orcid":"","institution":"Quanzhou Guangqian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Miaoyi","middleName":"","lastName":"Su","suffix":""},{"id":400494616,"identity":"7740cc7f-e9db-466b-be5a-18f4e9714ae0","order_by":8,"name":"Yongshi Shen","email":"","orcid":"","institution":"Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yongshi","middleName":"","lastName":"Shen","suffix":""},{"id":400494617,"identity":"c41c2219-7849-4525-97a9-a755a89789f9","order_by":9,"name":"Zhichao Fu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBAC+wMQmoeNmfngg4QKG8JaDEAEUJsMHztbssGDM2nEa7GR4+cxk3zYdogILexnjD9/qLgHdBiDWUUC2wEG/vbuBLxa7HlyzCQOnCkGaUm7kcBzh0HizNkNBByWY8ZwsC0BpOXYjQSJZwwGErkEtPC/Mf5w8B9IC2NbQYLBYSK0SOQYSBxsAGlhZmNISCBKy7MyiTPHQFrYmCUSDqTxEPYLf/LmDxU1Cfby/ec/fvz5DxjY7b34tWAAHtKUj4JRMApGwSjACgD/CUNQ+rDiugAAAABJRU5ErkJggg==","orcid":"","institution":"Fuzong Clinical Medical College (900th Hospital), Fujian Medical University","correspondingAuthor":true,"prefix":"","firstName":"Zhichao","middleName":"","lastName":"Fu","suffix":""}],"badges":[],"createdAt":"2025-01-09 14:08:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5797124/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5797124/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73788107,"identity":"0c9f6398-c1bd-419a-b5ff-1a33c175510a","added_by":"auto","created_at":"2025-01-14 16:33:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":48200,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient flowchart\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5797124/v1/738af590e8c40c4c6c4931c3.png"},{"id":73788109,"identity":"78f65624-8aa5-409e-ad15-91b78d990d4f","added_by":"auto","created_at":"2025-01-14 16:33:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":42428,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analysis for LA-ESCC patients in the nCIT group and the nCRT group. (A) Kaplan-Meier plot of disease free survival; (B) Kaplan-Meier plot of overall survival.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5797124/v1/c391d6432b91c8689596823e.png"},{"id":73789419,"identity":"ec4e4a68-ed22-4b6b-84b5-059aa2371ec2","added_by":"auto","created_at":"2025-01-14 16:41:46","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":82034,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup Survival Analysis for Lymph Node Positive and Non-cT4 Stage LA-ESCC Patients. (A) Disease-Freesurvival and (B) overall survival in LA-ESCC patients with lymph node positive status. (C) Disease-Freesurvival and (D) overall survival in LA-ESCC patients with non-cT4 stage.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5797124/v1/5445b712749a8f0c04b06502.png"},{"id":73789420,"identity":"7ab0f359-cfe6-450e-833d-9fa68b0eb78d","added_by":"auto","created_at":"2025-01-14 16:41:46","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":98648,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup Survival Analysis for LA-ESCC Patients by Pathological Status. (A) Disease-Freesurvival and (B) overall survival in patients with pCR. (C) Disease-Freesurvival and (D) overall survival in lymph node-negative patients. (E) Disease-Freesurvival and (F) overall survival in patients with clinical T4 stage (cT4).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5797124/v1/56ab6af6a3d37df04aa2bb8f.png"},{"id":73788115,"identity":"7af9b534-65cd-4d21-a7d6-2bdd6df4cfc7","added_by":"auto","created_at":"2025-01-14 16:33:47","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":51101,"visible":true,"origin":"","legend":"\u003cp\u003eUnivariate and Multivariate Cox Regression Analysis of Overall Survival for LA-ESCC Patients. (A) Univariate Cox regression analysis; (B) Multivariate Cox regression analysis.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-5797124/v1/3fffb1f4d8069ee13a65796b.png"},{"id":73788113,"identity":"0544be8d-5b98-4087-afcb-f27401660fc2","added_by":"auto","created_at":"2025-01-14 16:33:46","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":50589,"visible":true,"origin":"","legend":"\u003cp\u003eUnivariate and Multivariate Cox Regression Analysis of Disease-Free Survival for LA-ESCC Patients. (A) Univariate Cox regression analysis; (B) Multivariate Cox regression analysis.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-5797124/v1/3d97d2f7066d69c726356033.png"},{"id":87489046,"identity":"69ddcebe-7ce1-4bcb-894c-78051cbae73e","added_by":"auto","created_at":"2025-07-24 11:31:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1384883,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5797124/v1/e5c2d659-7800-40ab-a1e9-02e748fee588.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Analysis of Clinical Outcomes Between Neoadjuvant Chemoimmunotherapy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEsophageal cancer is one of the most common cancers globally, ranking seventh in incidence and sixth in mortality among all cancers\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in Asia\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e, accounting for over 84% of all esophageal cancer cases\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. In the early stages of esophageal cancer, patients often remain asymptomatic, leading to the majority being diagnosed at a locally advanced stage. Currently, esophagectomy is the primary treatment for patients with resectable locally advanced-ESCC (LA-ESCC). However, surgery alone often results in high recurrence rates and poor survival outcomes\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThere is growing evidence that neoadjuvant therapy can improve survival in patients with LA-ESCC. The CROSS clinical trial demonstrated that neoadjuvant chemoradiotherapy (nCRT) followed by surgery significantly improved overall survival (OS) in patients with LA-ESCC compared to surgery alone\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Similarly, the JCOG9907 clinical study compared the efficacy and safety of neoadjuvant chemotherapy (nCT) to adjuvant chemotherapy in treating LA-ESCC, finding that nCT significantly enhanced OS with an acceptable safety profile\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Immune checkpoint inhibitors (ICIs), such as PD-1 and PD-L1 inhibitors, have demonstrated efficacy in treating advanced ESCC and other cancers\u003csup\u003e[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Additionally, several preclinical studies have highlighted the synergistic effects of combining ICIs with chemotherapy or radiotherapy\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Despite these advancements, there is still a limited number of studies comparing the efficacy of nCRT versus neoadjuvant chemotherapy combined with immunotherapy (nCIT) in resectable LA-ESCC\u003csup\u003e[\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTherefore, this study aimed to compare the treatment responses and long-term survival outcomes of patients with resectable LA-ESCC who received nCRT versus nCIT followed by esophagectomy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eMethods and patients\u003c/h2\u003e \u003cp\u003e This study included patients with LA-ESCC who received either nCIT or nCRT, followed by esophagectomy, at three hospitals (the 900th Hospital, Fujian Cancer Hospital, and Quanzhou Guangqian Hospital) in China between November 2015 and January 2024. The inclusion criteria were: (1) age\u0026thinsp;\u0026gt;\u0026thinsp;18 years old; (2) ECOG score of 0 to 1; (3) thoracic ESCC with clinical stage from T2-4N0M0 or TanyN\u0026thinsp;+\u0026thinsp;M0 based on AJCC 8th; (4) completed neoadjuvant therapy followed by surgery; (5) postoperative pathologic diagnosis of squamous cell carcinoma; (6) No history of any antitumor therapy, such as targeted therapy or immunotherapy; and (7) Availability of complete clinical data and survival or follow-up information. The exclusion criteria were: (1) postoperative pathological diagnosis of non-squamous cell carcinoma; (2) incomplete neoadjuvant therapy or failure to undergo transthoracic esophagectomy following neoadjuvant therapy; (3) receipt of radical radiation therapy; (4) missing clinical data; and (5) presence of other concurrent malignant tumors. The study was approved by institutional ethics board of the 900th Hospital of the Joint Logistics Team (No. 2024-032) and individual consent for this retrospective analysis was waived.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTreatments\u003c/h3\u003e\n\u003cp\u003ePatients in the nCRT group received concurrent chemoradiotherapy. The radiotherapy regimen consisted of 40\u0026ndash;50 Gy, delivered in 20\u0026ndash;25 fractions, with 5 fractions per week. Concurrent chemotherapy included two options: (1) paclitaxel (45\u0026ndash;60 mg/m\u0026sup2;) combined with cisplatin (20\u0026ndash;25 mg/m\u0026sup2;) weekly, or (2) cisplatin (30 mg/m\u0026sup2;) combined with capecitabine (800 mg/m\u0026sup2;) weekly. Patients in the nCIT group received immunotherapy in combination with concurrent TP chemotherapy. Immunotherapy agents included toripalimab (240 mg every 3 weeks), camrelizumab (200 mg every 3 weeks), pembrolizumab (200 mg every 3 weeks), sintilimab (200 mg every 3 weeks), or tislelizumab (200 mg every 3 weeks). The TP chemotherapy regimen included albumin-bound paclitaxel (175 mg/m\u0026sup2;) or docetaxel (70 mg/m\u0026sup2;) combined with cisplatin (75 mg/m\u0026sup2;) or nedaplatin (75 mg/m\u0026sup2;), administered every 3 weeks. After completing neoadjuvant therapy, all patients in both the nCIT and nCRT groups underwent minimally invasive McKeown esophagectomy.\u003c/p\u003e\n\u003ch3\u003eEndpoints and assessments\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint was 3-year OS rate. Second endpoints included pCR, MPR, ORR, DFS and TRAEs. AEs were assessed according to the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0). MPR was defined as \u0026le;\u0026thinsp;10% residual viable tumor cells in the resected tumor bed, evaluated by H\u0026amp;E-stained slides. \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e pCR was defined as the absence of viable tumor cells in both the primary tumor site and resected lymph nodes.\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e OS was defined as the time from treatment to death from any cause, while DFS referred to the time from treatment to disease progression, recurrence at any site, or death from any cause.\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eCategorical variables were compared between the two groups using the chi-square test or Fisher\u0026rsquo;s exact test, and numerical variables were compared using the independent t-test. PSM was applied to minimize baseline differences between the nCIT and nCRT groups, adjusting for measured confounders.\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors for OS and DFS in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Kaplan-Meier survival curves and log-rank tests were used to compare OS and DFS between the two groups. Statistical analyses were performed using R software (version 4.4.1) and SPSS (version 27.0), with a significance threshold set at a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient clinical characteristics\u003c/h2\u003e\n \u003cp\u003eA total of 225 patients were included in this study, including 138 patients who received nCIT and 87 patients who received conventional nCRT as shown in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The median follow-up duration was 44.5 months for the nCIT group and 35.1 months for the nCRT group.\u003c/p\u003e\n \u003cp\u003eBaseline characteristics were presented in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The two groups differed significantly in age, smoking status, tumor location, and clinical T stage, but there were no significant differences in sex, alcohol history, clinical N stage, or clinical stage. To address baseline imbalances, a 1:1 case-control analysis was performed using PSM. After PSM adjustment, baseline characteristics were well-balanced between the two treatment groups, as shown in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Each group consisted of 87 patients following matching.\u003c/p\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBaseline feature,\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enCRT\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;87)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enCIT\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;138)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.927\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70 (80.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e113 (81.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17 (19.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25 (18.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years old)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53 (60.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64 (46.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34 (39.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74 (53.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65 (74.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75 (54.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22 (25.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e63 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrinking\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.153\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70 (80.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e98 (71.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17 (19.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40 (29.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor site\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eupper throacic segment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 (11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiddle thoracic segment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64 (73.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e84 (60.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003elower thoracic segment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38 (27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical T stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20 (14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e79 (90.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e100 (72.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 (11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical N stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.131\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28 (32.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32 (23.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31 (35.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40 (29.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25 (28.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e57 (41.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003cstrong\u003elinical stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅡ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30 (34.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33 (23.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅢ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49 (56.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e81 (58.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅣ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (9.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003enCIT: Neoadjuvant chemotherapy plus immunotherapy; nCRT: Neoadjuvant chemoradiotherapy.\u003c/p\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics after PSM\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBaseline feature,\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enCRT\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;87)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enCIT\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;87)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.852\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70 (80.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68 (78.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17 (19.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years old)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.285\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53 (60.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45 (51.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34 (39.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42 (48.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.318\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65 (74.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22 (25.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrinking\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.582\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70 (80.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66 (75.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17 (19.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21 (24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor site\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.465\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eupper thoracic segment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emiddle thoracic segment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64 (73.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59 (67.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003elower thoracic segment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17 (19.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical T stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.953\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e79 (90.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e78 (89.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical N stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.875\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28 (32.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25 (28.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31 (35.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25 (28.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30 (34.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.933\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅡ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30 (34.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28 (32.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅢ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49 (56.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50 (57.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅣ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (9.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003enCIT: Neoadjuvant chemotherapy plus immunotherapy; nCRT: Neoadjuvant chemoradiotherapy; PSM: Propensity score matching.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eEfficacy results\u003c/h3\u003e\n\u003cp\u003eAs presented in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, the nCRT group showed significantly better outcomes than the nCIT group in terms of ORR (85.06% vs. 45.98%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), postoperative T stage (78.16% vs. 58.62%, p\u0026thinsp;=\u0026thinsp;0.006) N stage descending rate (85.06% vs. 45.98%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as well as the pCR rate (37.9% vs 14.9%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTreatment responses of the two groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enCRT\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;87)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enCIT\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;87)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePR/CR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74(85.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40(46.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13(14.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47(54.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003epCR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33(37.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13(14.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54(62.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74(85.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMPR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51(58.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37(42.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36(41.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50(57.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative T stage descending\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68(78.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51(58.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19(21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36(41.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative N stage descending\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74(85.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40(46.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13(14.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47(54.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003enCIT: Neoadjuvant chemotherapy plus immunotherapy; nCRT: Neoadjuvant chemoradiotherapy; PSM: Propensity score matching; ORR: Objective response rate; pCR: Pathologic complete response; MPR: major pathological response.\u003c/p\u003e\n\u003cp\u003eThe 1-, 2-, and 3-year DFS and OS rates for the nCRT and nCIT are shown in Table 4, Additionally, nCIT group had longer OS and DFS compared to the nCRT group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Subgroup analysis revealed that patients with LA-ESCC and clinical N\u0026thinsp;+\u0026thinsp;or non-cT4 stage in the nCRT group had significantly longer mOS and mDFS (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). However, for patients with LA-ESCC and clinical N- or cT4 stage, there were no significant differences in OS and DFS between nCIT group and nCRT group (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). In addition, among patients with pCR, there was no significant difference in OS and DFS between the two treatment groups (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eTable 4. Long-term survival outcomes of the two groups\u003c/p\u003e\n\u003ctable id=\"Tabd\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enCIT\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enCRT\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1-year DFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91.72%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76.55%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2-year DFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76.73%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e55.09%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3-year DFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66.35%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47.32%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1-year OS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e96.43%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e88.27%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2-year OS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e82.49%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68.03%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3-year OS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75.89%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e55.57%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003enCIT: Neoadjuvant chemotherapy plus immunotherapy; nCRT: Neoadjuvant chemoradiotherapy; DFS: Disease-free survival; OS: Overall survival.\u003c/p\u003e\n\u003cp\u003eUnivariate and multivariate Cox regression analyses identified clinical N stage as an independent prognostic factor for OS and DFS. Specifically, for OS, the hazards ratios (HR) for N1, N2, and N3 were 2.27 (95% CI\u0026thinsp;=\u0026thinsp;1.04\u0026ndash;4.94, p\u0026thinsp;=\u0026thinsp;0.04), 2.65 (95% CI\u0026thinsp;=\u0026thinsp;1.23\u0026ndash;5.74, p\u0026thinsp;=\u0026thinsp;0.013), and 10.79 (95% CI\u0026thinsp;=\u0026thinsp;3.22\u0026ndash;36.17, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), respectively, as shown in Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e. For DFS, the HR for N2 was 1.93 (95% CI\u0026thinsp;=\u0026thinsp;1.04\u0026ndash;3.56, p\u0026thinsp;=\u0026thinsp;0.037), and for N3, the HR was 3.30 (95% CI\u0026thinsp;=\u0026thinsp;1.09\u0026ndash;9.98, p\u0026thinsp;=\u0026thinsp;0.035) as shown in Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e. These findings suggest that LA-ESCC patients with clinical N2 or N3 stage are at higher risk for tumor progression and have poorer prognosis.\u003c/p\u003e\n\u003ch3\u003eSafety results\u003c/h3\u003e\n\u003cp\u003eAEs in this study were defined as complications occurring from the initiation of neoadjuvant therapy through one week after surgery completion. As shown in Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e, after PSM, no statistically significant differences were observed in the incidence of myelosuppression of Grade\u0026thinsp;\u0026ge;\u0026thinsp;3 (16.09% vs. 17.24%), liver dysfunction of Grade\u0026thinsp;\u0026ge;\u0026thinsp;3 (2.30% vs. 0%), vomiting of Grade\u0026thinsp;\u0026ge;\u0026thinsp;3 (6.70% vs. 2.30%), pneumonia (36.78% vs. 24.14%), or esophageal fistula (1.15% vs. 3.45%) between the nCRT and nCIT groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTreatment related adverse events post neoadjuvant therapy\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTRAEs\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enCRT\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;87)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enCIT\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;87)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMyelosuppression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.839\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade 1/2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73(83.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72(82.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14(16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(17.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver dysfunction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.497\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade 1/2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e85(97.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87(1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eVomiting\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.278\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade 1/2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e81(93.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85(97.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6(6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePneumonia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32(36.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e55(63.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66(75.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEsophageal fistula\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.621\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1(1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86(98.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84(96.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003enCIT: Neoadjuvant chemotherapy plus immunotherapy; nCRT: Neoadjuvant chemoradiotherapy.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003enCIT, as a novel neoadjuvant therapeutic approach, has been demonstrated to exhibit definitive efficacy in various solid tumors, such as non-small cell lung cancer and triple-negative breast cancer\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. In the first reported multicenter clinical study, we observed that patients with LA-ESCC treated with nCIT followed by esophagectomy demonstrated better OS and DFS compared to those receiving nCRT followed by surgery. A retrospective study by Yu YK et al. which analyzed the efficacy of neoadjuvant therapy in 202 patients with LA-ESCC (81 receiving nCIT and 121 receiving nCRT), found that after adjustment for inverse probability of treatment weighting, the nCIT group had superior 3-year OS (91.70% vs. 79.80%; p\u0026thinsp;=\u0026thinsp;0.032) and 3-year DFS (87.40% vs. 72.80%; p\u0026thinsp;=\u0026thinsp;0.039) compared to the nCRT group, which was similar to the results of our study. However, contrasting findings have been reported in other single-center studies\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. Zhao et al. reported that the nCRT group had significantly superior DFS and OS compared to the nCIT group (12-month DFS: 94.30% vs. 81.80%, p\u0026thinsp;=\u0026thinsp;0.006; 12-month OS: 100.00% vs. 95.40%, p\u0026thinsp;=\u0026thinsp;0.032)\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. These mixed results underscore the need for further research to compare the efficacy of nCRT and nCIT in LA-ESCC.\u003c/p\u003e \u003cp\u003eOur study\u0026rsquo;s multivariate Cox regression analysis identified clinical N stage as an independent prognostic factor for both DFS and OS (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). With data from multiple centers and long-term follow-up, our research provides a robust comparison of these two treatment modalities, highlighting the potential long-term benefits of tumor immunotherapy. Subgroup analysis revealed that patients with N-positive disease had significantly longer DFS and OS in the nCIT group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), suggesting that nCIT may offer particular advantages for LA-ESCC patients with N-positive status. Patients with lymph node-positive status often have undetectable metastases in the bloodstream at the time of diagnosis\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Compared to the localized effects of radiotherapy, immunotherapy may reduce recurrence in this patient population through its systemic therapeutic effects.\u003c/p\u003e \u003cp\u003eA retrospective study comparing the feasibility and safety of nCRT plus surgery versus nCIT plus surgery in 64 patients with resectable LA-ESCC found that the nCRT group had better pathological responses, with a pCR rate of 43.80% vs. 18.80% and a MPR rate of 71.90% vs. 34.40% compared to the nCIT group\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Similarly, our study showed that the nCRT group had a higher pCR rate (37.90% vs. 14.90%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Furthermore, Another retrospective cohort study involving 44 patients (23 in the nCRT group and 21 in the nCIT group) found no significant difference in adverse event rates or post-surgery pathological remission rates between the two groups\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e, which contrasts with our findings in terms of pathological response, likely due to retrospective biases and small sample size. Previous study have shown that patients achieving pCR often experience prolonged DFS and OS\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. However, A meta-analysis indicated that patients with early-stage triple-negative breast cancerwho achieved pathological complete response (defined as ypT0, ypN0 or ypT0/is ypN0) demonstrated improved survival rates\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. The KEYNOTE-585 study also have shown that combining immunotherapy with chemotherapy increased the pCR rate by 10% compared to the chemotherapy-alone group, but neither EFS nor OS reached the predefined endpoints\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. It is important to recognize that pCR does not always equate to optimal outcomes. Neoadjuvant therapies can cause adverse effects, such as cardiotoxicity, which may diminish patients\u0026rsquo; quality of life. Additionally, even in cases where pCR is achieved, micrometastatic disease or minimal residual cancer may persist, potentially leading to recurrence or metastasis and, ultimately, treatment failure. Consequently, while pCR rates are valuable, greater emphasis should be placed on DFS and OS as comprehensive measures of therapeutic success.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, as a retrospective analysis, the results may still be subject to inherent biases despite the application of PSM to mitigate them. Additionally, the relatively small sample size limits the robustness of the findings, highlighting the need for larger studies. Furthermore, the follow-up period is limited, requiring longer follow-up to more accurately assess long-term survival outcomes. We plan to continue monitoring patient survival and update the findings in future studies.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eNeoadjuvant chemoimmunotherapy followed by surgery is well tolerated and effective treatment option for locally advanced resectable esophageal squamous cell carcinoma, especially for patients with lymph node-positive disease.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no potential conflicts of interest or financial relationships related to the conduct of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw data from this study are not publicly available to protect patient privacy. For access to the research data, please contact the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhichao Fu, Xue Yan and Yongshi Shen concepted and designed the study; Data collection was done by Ying Peng and Peng Mo; formal analysis was done by Xue Yan, Ying Peng, Miaoyi Su, Liuyu Li, Weijing Jing, Wenzhen Zhang, Peng Mo, Yuanji Xu.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of 900th hospital of the Joint Logistics Team (2024-032).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Natural Science Foundation of Fujian Province (grant number: 2021J011259).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSung H, Ferlay J, Siegel RL, et al. 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Lancet Oncol. 2024;25(2):212\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Locally advanced resectable esophageal squamous cell carcinoma, Neoadjuvant chemoradiotherapy, Immunotherapy, Survival","lastPublishedDoi":"10.21203/rs.3.rs-5797124/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5797124/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePatients with locally advanced esophageal squamous-cell carcinoma (LA-ESCC) generally experience poor prognosis after surgery. Neoadjuvant therapy has shown potential to improve survival outcomes. This study aimed to compare the long-term efficacy and safety of neoadjuvant chemoimmunotherapy (nCIT) versus neoadjuvant chemoradiotherapy (nCRT) in patients with LA-ESCC.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis multicenter study included patients with LA-ESCC treated at three hospitals in China between November 2015 and January 2024. Patients underwent either nCIT or nCRT followed by surgical resection. The primary endpoint was the 3-year overall survival (OS) rate. Secondary outcomes included objective response rate (ORR), pathologic complete response (pCR) rate, major pathologic response, disease-free survival (DFS), OS, and treatment-related adverse events. Propensity score matching was employed to adjust for baseline differences.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 225 LA-ESCC patients were included in this study, with 87 patients receiving nCRT and 138 patients receiving nCIT. After propensity score matching adjustment, each group have 87 patients included. The nCRT group demonstrated significantly superior outcomes to nCIT group in terms of ORR (85.06% vs. 45.98%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), T stage down rate (78.16% vs. 58.62%, p\u0026thinsp;=\u0026thinsp;0.006), N stage down rate (85.06% vs. 45.98%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and pCR rate (37.90% vs 14.90%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The median follow-up duration was 44.5 months for the nCIT group and 35.1 months for the nCRT group. The nCIT group exhibited better 3-year OS (75.90% vs 55.60%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) andDFS (66.40% vs. 47.30%, P\u0026thinsp;=\u0026thinsp;0.009) compared to the nCRT group. Subgroup analysis indicated that LA-ESCC patient with N\u0026thinsp;+\u0026thinsp;or non cT4 stage who received neoadjuvant chemoradiotherapy followed by esophagectomy had better OS and DFS. Univariate and multivariate Cox regression analyses identified clinical N stage as an independent prognostic factor for both OS and disease-free survival across both cohorts.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003e Neoadjuvant chemoimmunotherapy followed by esophagectomy is a promising treatment strategy for locally advanced resectable esophageal squamous cell carcinoma. nCRT may provide greater benefits in patients with N\u0026thinsp;+\u0026thinsp;or non-cT4 stage disease.\u003c/p\u003e","manuscriptTitle":"Comparative Analysis of Clinical Outcomes Between Neoadjuvant Chemoimmunotherapy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-14 16:33:41","doi":"10.21203/rs.3.rs-5797124/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"19b2ed6e-5a3d-4c3d-8e94-bb94540d7e5c","owner":[],"postedDate":"January 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-24T11:23:49+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-14 16:33:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5797124","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5797124","identity":"rs-5797124","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}