Effective surgical conversion after neoadjuvant immunochemotherapy improves clinical outcomes in borderline resectable esophageal cancer

Effective surgical conversion after neoadjuvant immunochemotherapy improves clinical outcomes in borderline resectable esophageal cancer | 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 Effective surgical conversion after neoadjuvant immunochemotherapy improves clinical outcomes in borderline resectable esophageal cancer Binwen Xu, Chengcheng Zhang, Tao Luo, Yue Zhang, Liwen Zhang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6786605/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 : Immune checkpoint inhibitors have demonstrated preliminary safety and efficacy in treating borderline resectable esophageal squamous cell carcinoma (BR-ESCC). We aimed to compare treatment and survival outcomes between patients with locally advanced resectable ESCC (cT3r) and those with borderline resectable ESCC (cT3br) who underwent surgery following neoadjuvant immunochemotherapy (NICT). Methods : After NICT, 12 patients in the cT3br group were deemed unresectable, while 102 patients with clinically staged T3 ESCC underwent surgery and were included in the study. Patients were categorized into cT3r and cT3br groups based on the likelihood of adjacent vital organ invasion as observed on pre-treatment CT scans. Results : Among the participants, 52 patients were included in the cT3br group and 62 in the cT3r group. The surgical conversion rate for cT3br tumors was 76.9% (40/52). Both groups exhibited comparable outcomes in terms of surgical treatment and postoperative complications ( P > 0.05). Although the non-R0 resection rate was significantly higher in the cT3br group than in the cT3r group (20.0% vs 3.2%, P = 0.005), no significant differences were observed in postoperative overall survival (OS) or disease-free survival (DFS) between the two groups (3-year OS: 76% vs 67%, P = 0.453; 3-year DFS: 69% vs 47%, P = 0.155). Non-R0 resection was significantly associated with worse OS ( P = 0.001) and showed a trend toward association with DFS ( P = 0.069). Conclusion : Surgery following NICT is an effective treatment strategy for BR-ESCC, achieving treatment outcomes and survival prognoses comparable to those in patients with cT3r. borderline resectable esophageal squamous cell carcinoma，neoadjuvant immunochemotherapy，neoadjuvant chemoradiotherapy，R0 resection surgical outcomes Figures Figure 1 Figure 2 Figure 3 Introduction Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy that poses a significant threat to global health. 1 , 2 Due to the absence of prominent clinical symptoms in early esophageal cancer, most patients are diagnosed at a locally advanced stage. In China and some Western countries, neoadjuvant chemoradiotherapy (NRCT) is considered the standard treatment for locally advanced resectable ESCC, while radical chemoradiotherapy is advocated for advanced unresectable cases. 3 , 4 However, the optimal treatment strategy for borderline resectable ESCC remains uncertain, largely due to challenges in accurately determining the feasibility of complete tumor resection. 5 , 6 In 2022, the Japanese Esophageal Society (JES) introduced the T3 substage into the 12th edition of the Esophageal Cancer Classification 7 , subdividing it into locally advanced resectable (cT3r) and borderline resectable (cT3br) categories. Studies have suggested that surgical outcomes after NRCT in patients with cT3br are comparable to those with cT3r. 8 , 9 In the era of immunotherapy, neoadjuvant immunochemotherapy (NICT) has demonstrated higher pathological complete response (pCR) rates and better survival outcomes than NRCT. 10 – 13 Several single-arm studies have highlighted the prospective efficacy of immune checkpoint inhibitors for the neoadjuvant treatment of BR-ESCC, reporting induction-to-surgery conversion rates of 67.5%-71.0%, R0 resection rates of 81.8%-95%, and manageable toxicity. However, data on control groups and survival outcomes remain limited. 14 – 16 Therefore, investigating the differences in outcomes between patients with cT3r and cT3br treated with NICT is of substantial interest. We aimed to compare surgical outcomes and survival prognoses of patients with cT3r and cT3br treated with NICT. Methods Patients This retrospective study included 114 patients with ESCC who received NICT treatment between December 2020 and July 2023 at the thoracic surgery department. All patients were diagnosed with ESCC through preoperative biopsy, with a primary tumor clinical tumor stage of at least cT3. Patients were excluded if they had a clinical stage of cT4b or cT1-2, did not undergo surgery following induction therapy, had a history of other anticancer treatments, or presented with distant metastases (including supraclavicular lymph nodes). A flowchart outlining the patient screening process is shown in Fig. 1. Pathological staging followed the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) Staging System. The study was approved by the hospital's ethics committee and conducted in accordance with the 2013 Declaration of Helsinki. Written informed consent was waived (File number: 2024ER743-1). Definition of staging and margin-resectable tumors Clinical staging and treatment efficacy evaluations before and after neoadjuvant therapy were conducted by a m ultidisciplinary treatment (MDT) team using esophagoscopy, esophageal barium swallow, enhanced computed tomography (CT), and neck and abdominal ultrasonography. Based on the 12th edition of the Japanese Classification of Esophageal Cancer, cT3br thoracic ESCC was defined as a tumor with uncertain invasion into organs like the aorta, trachea, and pulmonary veins. 7 Tracheal invasion was suspected if tracheal wall compression or deformation was observed, and fiberoptic bronchoscopy was performed to rule out definitive intratracheal lesions. Aortic invasion was suspected if partial loss of the fat plane between the lesion’s outermost layer and the aorta was observed, along with an angle between the lesion and the aortic centerline of greater than 60° or less than 90°. 14 Pulmonary vein invasion was indicated by partial loss of the fat plane and substantial protrusion into the pulmonary veins. Fig. 2 provides representative cases of cT3r and cT3br thoracic ESCC. Neoadjuvant therapy regimens and surgery Neoadjuvant chemotherapy regimens included nedaplatin (80 mg/m², IV, day 1) combined with either docetaxel (70 mg/m², IV, day 2) or albumin-bound paclitaxel (200 mg/m², IV, day 2), along with concurrent immunotherapy selected based on patient preference, including sintilimab, camrelizumab, and tislelizumab. All patients underwent two cycles of NICT, with each cycle administered at intervals exceeding 21 days. Tumor resectability was assessed post-treatment through multidisciplinary consultation. Patients deemed suitable for radical resection underwent McKeown esophagectomy with second- or third-field lymph node dissection. Postoperatively, patients were followed up every 3 months during the first 2 years and every 6 months thereafter. Observational results Primary endpoints included the induction-to-surgery conversion rate and the R0 resection rate. The conversion success rate was defined as the proportion of patients with cT3br deemed operable following induction therapy. R0 resection was defined as the microscopic absence of cancer cells at resection margins on pathological slides. Secondary endpoints included overall survival (OS), disease-free survival (DFS), pCR, radiological response rate, and safety. OS was defined as the time from surgery to death from any cause. DFS was the time from surgery to recurrence or death from any cause. pCR was defined as the absence of residual tumor cells in the resected primary tumor or regional lymph nodes. Post-treatment pathological classifications based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 included partial response (PR), progressive disease (PD), and stable disease (SD). Statistical analysis Clinical characteristics were compared using the chi-square test, Fisher’s exact test, and student’s t-test. Data analysis was performed using SPSS software (version 29.0). Kaplan–Meier survival analysis curves were used to assess PFS and OS, and the log-rank test was used to compared survival differences between the groups. Kaplan–Meier survival curves were generated using R software (version 4.3.2). All statistical tests were two-tailed, with a P value < 0.05 considered significant. Result Baseline characteristics After NICT, 12 patients in the cT3br group were deemed unresectable. A total of 102 patients underwent radical surgery and were included in the analysis. The surgical conversion rate after NICT was 76.9% (40/52), with 62 and 40 patients in the cT3r and cT3br groups, respectively. Table 1 indicates no significant differences in baseline characteristics, such as age, sex, BMI, and clinical N stage, between the two groups. However, primary tumor locations differed significantly ( P = 0.025). In the cT3br group, the tumor was primarily located in the middle (85%) and upper esophagus (10%), while in the cT3r group, it was predominantly located in the middle (64.5%) and lower esophagus (25.8%). Radiological evaluations revealed no significant differences in treatment response between the groups ( P = 0.111). Table 1 shows that 41 patients (66.1%) in the cT3r group achieved a partial response (PR) after two cycles of NICT compared to 33 patients (82.5%) in the cT3br group. Table. 1 Clinical characteristics of the patients of cT3r and cT3br Variables cT3r (n=62) cT3br (n=40) P -value Age, mean ± SD，year 63.60 ± 7.02 64.65 ± 9.41 0.520 Sex Male 49 (79.0%) 29 (72.5%) 0.480 Female 13 (21.0%) 11 (27.5%) BMI ≤ 22.9 36 (58.1%) 29 (72.5%) 0.139 ＞22.9 26 (41.9%) 11 (27.5%) Tumor location Upper 6 (9.7%) 4 (10%) 0.025 Middle 40 (64.5%) 34 (85%) Lower 16 (25.8%) 2 (5.0%) Suspected organ invasion Aorta - 15 (37.5%) - Trachea and bronchus - 29 (72.5%) Pulmonary vein - 6 (15.0%) Chemotherapy regime Docetaxel 13 (21.0%) 20 (50.0%) 0.002 Nab-paclitaxel 49 (79.0%) 20 (50.0%) Immunotherapy regime Camrelizumab 15 (24.2%) 10 (25.0%) 1.000 Sintilimab 39 (62.9%) 26 (65.0%) Tislelizumab 6 (9.7%) 3 (7.5%) Toripalimab 2 (3.2%) 1 (2.5%) Clinical N stage N0 30 (48.4%) 14 (35.0%) 0.131 N1 25 (40.3%) 24 (60.0%) N2-3 7 (11.3%) 2 (5.0%) Clinical response PR 41 (66.1%) 33 (82.5%) 0.111 SD/PD 21 (33.9%) 7 (17.5%) ＊PR, Partial Response；PD, Progression Disease；SD, Stale Disease. Surgical outcomes Table 2 summarizes surgical and postoperative pathological outcomes. Surgical duration was comparable between the cT3r and cT3br groups (208.5 minutes vs. 205.2 minutes, P = 0.259). Intraoperative blood loss, number of lymph nodes dissected, and postoperative hospital stays were also comparable between the two groups ( P > 0.05). Tumors in the cT3br group had a significantly higher likelihood of adjacent organs invasion than those in the cT3r group (20.0% vs. 9.7%, P = 0.02). Intraoperative and postoperative pathological findings revealed that in the cT3br group, 7 cases (11.3%) showed bronchial invasion, 1 case (2.5%) showed aortic invasion, and 1 case (2.5%) showed pericardial invasion. In the cT3r group, bronchial invasion was observed in 2 cases (3.2%), mediastinal pleura invasion in 2 cases (1.6%), and diaphragm, lung, and thoracic duct invasion in 1 case each (1.6%). The non-R0 resection rate was significantly higher in the cT3br group than in the cT3r group (20.0% vs. 3.2%, P = 0.005). No significant differences were observed between the two groups regarding the pCR rate or postoperative pathological staging ( P = 0.499 and P = 0.914, respectively). As shown in Table 3, pulmonary infection was the most common postoperative complication in both groups, although the difference was not statistically significant (cT3r, 22.6% vs. cT3b, 35%; P = 0.179). Similarly, there were no significant differences between the groups in terms of other complications, including anastomotic leakage, chylothorax, and respiratory failure ( P > 0.05). Table. 2 Surgical and pathological result between cT3r and cT3br Variables cT3r (n=62) cT3br (n=40) P -value Operation time, median (range),min 208.5 (190.2-235.5) 205.2 (177.8-233.4) 0.259 Blood loss, median (range), ml 80.0 (50.0-100.0) 100.0 (50.0-115.0) 0.276 No.of LNs harvested, mean ± SD 21.10 ± 9.02 20.08 ± 9.79 0.590 POLS, median (range), days 8.0 (7.0-9.25) 9.0 (8.0-10.0) 0.210 Resection margins R0 60（96.8%） 32（80.0%） 0.005 R1/2 2（3.2%） 8（20.0%） Pathological CR pCR 12（19.4%） 10（25.0%） 0.499 Non-pCR 50（80.6%） 30（75%） Pathological organ invasion None 56（90.3%） 32（80.0%) 0.020 Diaphragm/Thoracic Duct/Lung/Pleura 5（8.0%） 1 (2.5%) Aorta 0 1 (2.5%) Trachea and bronchus 2（3.2%） 7 (11.3%) Pulmonary vein 0 0 ypTNM stage I 26 (41.9%) 19 (47.5%) 0.914 II 4 (6.5%) 2 (5.0%) IIIA 8 (12.9%) 5 (12.5%) IIIB 16 (25.8%) 5 (12.5%) IVA 8 (12.9%) 9 (22.5%) Postoperative adjuvant therapy Yes 27 (43.5%) 21 (52.5%) 0.377 No 35 (56.5%) 19 (47.5%) Recurrence after surgery None 40 (64.5%) 30 (75.0%) 0.491 Loco-regional 2 (3.2%) 0 Distant 15 (24.2%) 6(15.0%) Loco-regional and Distant 5 (8.1%) 4 (10.0%) ＊LN, lymph node; POLS, Postoperative Length of Stay; pCR, Pathological complete response Table. 3 Complications after surgical treatment. Variables cT3r (n=62) cT3br (n=40) P -value Pulmonary infection Present 14 (22.6%) 14 (35.0%) 0.170 Absent 48 (77.4%) 26 (65.0%) Anastomotic leakage Present 1 (1.6%) 0 1.000 Absent 61 (98.4%) 40 (100%) Chylothorax Present 0 0 1.000 Absent 62 (100%) 40 (100%) Respiratory failure Present 0 1 (2.5%) 0.392 Absent 62 (100%) 39 (97.5%) Survival outcomes and recurrence patterns The median follow-up duration was 30.5 months (95% CI, 23.98–37.02). As shown in Fig. 3, the 3-year OS and DFS rates were 67% and 47% for the cT3r group, respectively, and 76% and 69% for the cT3br group, with no statistically significant differences ( P = 0.453; P = 0.155). Conversely, non-R0 resection was significantly associated with worse OS (3-year OS; R0 75% vs non-R0 16%, P = 0.001) and showed a near-significant trend in DFS (3-year DFS; R0 60% vs non-R0 29%, P = 0.069). This study also analyzed the postoperative failure patterns in the two groups. As shown in Table 2, 7 patients in the cT3r group experienced local recurrence, and 20 developed distant metastases; in the cT3br group, 4 cases of local recurrence and 10 cases of distant metastases were observed, with no statistically significant differences in recurrence rates (35.5% vs 25%, P = 0.491). Furthermore, the cT3br group received more aggressive adjuvant therapies than the cT3r group, although this difference was not statistically significant (52.5% vs 43.5%, P = 0.377). Discussion This study compared the surgical outcomes and survival prognoses of the patients with cT3r and cT3br esophageal squamous cell carcinoma following NICT. To the best of our knowledge, this is the first study to evaluate the treatment outcomes of these two groups under the NICT regimen. Two key findings emerged: (1) with the NICT regimen, the induction-to-surgery conversion rate for BR-ESCC was 76.9% (40/52). Due to the potential invasion into adjacent vital organs in the cT3br group, the non-R0 resection rate was significantly higher than in the cT3r group. (2) Despite higher malignancy in the cT3br group, treatment outcomes and survival prognoses were comparable to those of the cT3r group after surgery. These findings suggest that for patients with BR-ESCC, the primary treatment strategy should focus on selecting induction regimens that maximize surgical conversion rates and improve R0 resection rates. Landmark studies, such as the CROSS and NEOCRTE5010, have established the pivotal role of NRCT in managing locally advanced ESCC. 3 , 17 However, the optimal preoperative treatment strategy for BR-ESCC remains unclear due to its unique imaging and anatomical characteristics. NEOCRTEC-1601, a single-center phase II clinical trial evaluated surgical outcomes following docetaxel, cisplatin, and fluorouracil (TPF) chemotherapy for BR-ESCC. 18 After 2–3 cycles of TPF treatment, the study reported an induction-to-surgery conversion rate of 57.4% (27/47), with 25 patients (53.2%) achieving R0 resection and a 3-year OS rate of 54.4%. Similarly, TOMOYA et al. 19 demonstrated that DCF triple-drug chemotherapy significantly improved surgical conversion rate (81.2% vs 71.4%) and R0 resection rates (62.5% vs 37.5%) compared to the FP regimen, without increasing surgical complications or toxicities apart from myelosuppression. Unlike simple induction chemotherapy regimens, several studies have assessed the efficacy of NRCT for the treatment of BR-ESCC. A Japanese retrospective study 20 showed that among 50 patients with BR-ESCC undergoing neoadjuvant chemoradiotherapy (NACRT), 27 (54%) successfully achieved induction conversion therapy, with an R0 resection rate of 81.4% (22/27). The study also identified elevated pre-NACRT serum SCC antigen levels as predictive of treatment failure and poor survival. However, we argue that NRCT may not be optimal for patients with BR-ESCC. As highlighted in our previous study, localized effects of radiotherapy can induce edema and fibrosis in the tumor region, complicating clinical staging. This inflammatory edema may hinder the short-term assessment of post-treatment resectability, leading to delayed interventions or missed surgical opportunities. 14 , 21 Immune checkpoint inhibitors are emerging antitumor agents that primarily eradicate cancer cells by reactivating cytotoxic T cells. 2 , 22 – 23 However, clinical data on the efficacy of immunotherapy for BR-ESCC remains relatively limited. A prospective single-center phase II study (ChiCTR2200056728) demonstrated 15 that preoperative camrelizumab combined with chemotherapy achieved a 71% induction-to-surgery conversion rate (22/31), with 81.8% of patients (18/22) undergoing R0 resection. Our findings align with these results. With a median follow-up of 30.5 months (95% CI, 23.98–37.02), the cT3br group exhibited 3-year OS and DFS rates of 76% and 69%, respectively. Notably, despite the higher malignancy rate in the cT3br group, the cT3r group did not show a postoperative survival advantage (OS, P = 0.453; DFS, P = 0.155). This consistency with prior studies, including those by Ryosuke 8 and Akiyuki 9 on NRCT in BR-ESCC, may be attributed to the more aggressive adjuvant treatments administered to cT3br group patients at our center postoperatively. Nonetheless, this suggests that successful induction conversion surgery allows patients with BR-ESCC to achieve surgical outcomes and long-term survival comparable to those with cT3r. Additionally, since the cT3br group patients may exhibit potentially have invasion of adjacent vital organs, enhancing the R0 resection rate is particularly critical. This underscores the need for future research to further treatment strategies for BR-ESCC. This study had some limitations. Firstly, as a single-center retrospective study with limited sample size and heterogeneous chemotherapy and immunotherapy regimens, these findings require validation in large-scale, multicenter prospective studies. Second, there is no consensus on the diagnostic criteria for BR-ESCC. Although patient grouping in this study was performed using multidisciplinary evaluations, subjectivity and variability may have influenced the process. Finally, due to the limited baseline clinical data available, we could not analyze preoperative risk factors for non-R0 resection in surgical patients, which are crucial for developing effective treatment strategies for BR-ESCC. Conclusion In conclusion, NICT appears to be an effective treatment strategy for BR-ESCC, providing high surgical conversion rates, favorable surgical outcomes, and long-term survival comparable to patients with cT3r. Future treatment strategies for BR-ESCC should prioritize improving surgical conversion success and enhancing R0 resection rates. Abbreviations BR-ESCC Borderline resectable esophageal squamous cell carcinoma NICT Neoadjuvant immunochemotherapy OS Overall survival DFS Disease-free survival NRCT Neoadjuvant chemoradiotherapy MDT Multidisciplinary treatment CT Computed tomography PR Partial response PD Progressive disease SD Stable disease pCR Pathological complete remission Declarations Ethics approval and consent to participate This study was reviewed and approved by the Ethics Committee of Affiliated Hospital of North Sichuan Medical College. According to national legislation and institutional requirements, written informed consent was not required for participation in this study. (File number: 2024ER743-1). Consent for publication Not applicable Availability of data and materials The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors. Competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding This study was funded by the Nanchong City University Science and Technology Strategic Cooperation Special Fund (Grant No. 22SXQT0095) and the Scientific Research Foundation for Advanced Talents, Affiliated Hospital of North Sichuan Medical College (Grant No. 2023GC006) Authors' contributions BX: Conceptualization, Data curation, Methodology, Writing - original draft, Writing - review & editing. CZ: Conceptualization, Investigation, Methodology, Writing - review & editing. TL: Data curation, Investigation, Methodology, Writing - review & editing. YZ: Data curation, Investigation, Methodology, Writing - review & editing. LZ: Data curation, Investigation, Methodology, Writing - review & editing. JL: Conceptualization, Methodology, Supervision, Writing - review & editing. GS: Conceptualization, Funding acquisition, Supervision, Writing - review & editing. MF: Conceptualization, Project administration, Supervision, Visualization, Writing - review & editing. Acknowledgements We would like to thank Editage (www.editage.cn) for English language editing. References Njei B, McCarty T R, Birk J W. Trends in esophageal cancer survival in United States adults from 1973 to 2009: a SEER database analysis. Journal of Gastroenterology and Hepatology , 2016, 31(6): 1141-1146. Yang J, Liu X, Cao S, Dong X, Rao S, Cai. Understanding Esophageal Cancer: The Challenges and Opportunities for the Next Decade. Frontiers in Oncology , 2020, 10: 1727. Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, et al. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. Journal of Clinical Oncology , 2018, 36(27): 2796-2803. 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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-6786605","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":471357447,"identity":"1b103976-df2c-4213-8fba-972a81bf3300","order_by":0,"name":"Binwen Xu","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Binwen","middleName":"","lastName":"Xu","suffix":""},{"id":471357448,"identity":"f52f1e4e-1958-4b51-867f-f509997f6acf","order_by":1,"name":"Chengcheng Zhang","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Chengcheng","middleName":"","lastName":"Zhang","suffix":""},{"id":471357449,"identity":"c01bb0ae-b6ca-426e-89f8-4f26f483af76","order_by":2,"name":"Tao Luo","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Luo","suffix":""},{"id":471357450,"identity":"a97ccb47-8415-4b64-ac47-604b691c6c30","order_by":3,"name":"Yue Zhang","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Yue","middleName":"","lastName":"Zhang","suffix":""},{"id":471357451,"identity":"4e4c20ac-7bd4-4746-8cd0-e59f35d619b0","order_by":4,"name":"Liwen Zhang","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Liwen","middleName":"","lastName":"Zhang","suffix":""},{"id":471357452,"identity":"1ca8241a-7698-4fd0-be28-85fee5b6a691","order_by":5,"name":"Junhong Liu","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Junhong","middleName":"","lastName":"Liu","suffix":""},{"id":471357453,"identity":"3f2d8d57-31e5-47d7-9417-045a3622bca7","order_by":6,"name":"Guidong Shi","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Guidong","middleName":"","lastName":"Shi","suffix":""},{"id":471357454,"identity":"35bbe1b6-5350-4ff9-9581-2bb84e17ee68","order_by":7,"name":"Maoyong Fu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBAC9gYE2/BBQkUNYS08BxBsY4MHZ46RpsVM8mELMxFaJLITP3xss8mTDzu8rSKxgY2Bv707gYCW3M2SM9vSig1vp5XdSNwhwyBx5uwGvFrsJXI3SPO2HU7cODvH7EbiGTYGA6AIQVt+w7QUJLYxE6VlG9iW+dI5ZgzEaeF5u81yxrm0xA3SacUSCWeO8RD0Cw977uYbH8psEufPTt748UdFjRx/ey9+LWDAyMbAYHAAagZh5WDwh4FBvoFItaNgFIyCUTDyAAC3i0uaGhBfzQAAAABJRU5ErkJggg==","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":true,"prefix":"","firstName":"Maoyong","middleName":"","lastName":"Fu","suffix":""}],"badges":[],"createdAt":"2025-05-30 17:08:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6786605/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6786605/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84809990,"identity":"144593a7-087e-413f-9859-4588f9760114","added_by":"auto","created_at":"2025-06-17 14:45:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":61247,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study.\u003c/p\u003e","description":"","filename":"Figure.1.png","url":"https://assets-eu.researchsquare.com/files/rs-6786605/v1/ceca330d04cfeb6ab507468d.png"},{"id":84811351,"identity":"37144396-fb2e-49aa-a53d-613f0ccdb472","added_by":"auto","created_at":"2025-06-17 14:53:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1377981,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative images of cT3r and cT3br. \u003cstrong\u003ea-c\u003c/strong\u003e cT3r is adjacent to the bronchus/pulmonary vein/aorta, yet no invasion is observed. \u003cstrong\u003ed-f\u003c/strong\u003e cT3br is immediately adjacent to the bronchus/pulmonary vein/aorta with possible invasion\u003c/p\u003e","description":"","filename":"Figure.2.png","url":"https://assets-eu.researchsquare.com/files/rs-6786605/v1/41051df90e0375a12121bdd9.png"},{"id":84809997,"identity":"9bf56149-13dc-415d-b659-d1075a545ade","added_by":"auto","created_at":"2025-06-17 14:45:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":224821,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival analysis of OS (a) and DFS (b) between cT3r and cT3br; Kaplan-Meier survival analysis of OS (c) and DFS (d) between R0 and non-R0\u003c/p\u003e","description":"","filename":"Figure.3.png","url":"https://assets-eu.researchsquare.com/files/rs-6786605/v1/c6496ce74f1039ffc32fbdae.png"},{"id":89692015,"identity":"3f475f04-6039-4d68-a4fd-380732cabc19","added_by":"auto","created_at":"2025-08-22 17:01:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2313215,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6786605/v1/28d54484-9027-4805-91b3-0fb4587139b6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effective surgical conversion after neoadjuvant immunochemotherapy improves clinical outcomes in borderline resectable esophageal cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEsophageal squamous cell carcinoma (ESCC) is a prevalent malignancy that poses a significant threat to global health. \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Due to the absence of prominent clinical symptoms in early esophageal cancer, most patients are diagnosed at a locally advanced stage. In China and some Western countries, neoadjuvant chemoradiotherapy (NRCT) is considered the standard treatment for locally advanced resectable ESCC, while radical chemoradiotherapy is advocated for advanced unresectable cases.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e However, the optimal treatment strategy for borderline resectable ESCC remains uncertain, largely due to challenges in accurately determining the feasibility of complete tumor resection.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e In 2022, the Japanese Esophageal Society (JES) introduced the T3 substage into the 12th edition of the Esophageal Cancer Classification\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, subdividing it into locally advanced resectable (cT3r) and borderline resectable (cT3br) categories. Studies have suggested that surgical outcomes after NRCT in patients with cT3br are comparable to those with cT3r.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e In the era of immunotherapy, neoadjuvant immunochemotherapy (NICT) has demonstrated higher pathological complete response (pCR) rates and better survival outcomes than NRCT.\u003csup\u003e\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Several single-arm studies have highlighted the prospective efficacy of immune checkpoint inhibitors for the neoadjuvant treatment of BR-ESCC, reporting induction-to-surgery conversion rates of 67.5%-71.0%, R0 resection rates of 81.8%-95%, and manageable toxicity. However, data on control groups and survival outcomes remain limited.\u003csup\u003e\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Therefore, investigating the differences in outcomes between patients with cT3r and cT3br treated with NICT is of substantial interest. We aimed to compare surgical outcomes and survival prognoses of patients with cT3r and cT3br treated with NICT.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study included 114 patients with ESCC who received NICT treatment between December 2020 and July 2023 at the thoracic surgery department. All patients were diagnosed with ESCC through preoperative biopsy, with a primary tumor clinical tumor stage of at least cT3. Patients were excluded if they had a clinical stage of cT4b or cT1-2, did not undergo surgery following induction therapy, had a history of other anticancer treatments, or presented with distant metastases (including supraclavicular lymph nodes). A flowchart outlining the patient screening process is shown in Fig. 1. Pathological staging followed the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) Staging System. The study was approved by the hospital\u0026apos;s ethics committee and conducted in accordance with the 2013 Declaration of Helsinki. Written informed consent was waived (File number: 2024ER743-1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition of staging and margin-resectable tumors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical staging and treatment efficacy evaluations before and after neoadjuvant therapy were conducted by a m\u003cem\u003eultidisciplinary treatment (MDT) team\u0026nbsp;\u003c/em\u003eusing esophagoscopy, esophageal barium swallow, enhanced computed tomography (CT), and neck and abdominal ultrasonography. Based on the 12th edition of the Japanese Classification of Esophageal Cancer, cT3br thoracic ESCC was defined as a tumor with uncertain invasion into organs like the aorta, trachea, and pulmonary veins.\u003csup\u003e7\u003c/sup\u003e Tracheal invasion was suspected if tracheal wall compression or deformation was observed, and fiberoptic bronchoscopy was performed to rule out definitive intratracheal lesions. Aortic invasion was suspected if partial loss of the fat plane between the lesion\u0026rsquo;s outermost layer and the aorta was observed, along with an angle between the lesion and the aortic centerline of greater than 60\u0026deg; or less than 90\u0026deg;. \u003csup\u003e14\u003c/sup\u003e Pulmonary vein invasion was indicated by partial loss of the fat plane and substantial protrusion into the pulmonary veins. Fig. 2 provides representative cases of cT3r and cT3br thoracic ESCC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNeoadjuvant therapy regimens and surgery\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNeoadjuvant chemotherapy regimens included nedaplatin (80 mg/m\u0026sup2;, IV, day 1) combined with either docetaxel (70 mg/m\u0026sup2;, IV, day 2) or albumin-bound paclitaxel (200 mg/m\u0026sup2;, IV, day 2), along with concurrent immunotherapy selected based on patient preference, including sintilimab, camrelizumab, and tislelizumab. All patients underwent two cycles of NICT, with each cycle administered at intervals exceeding 21 days. Tumor resectability was assessed post-treatment through multidisciplinary consultation. Patients deemed suitable for radical resection underwent McKeown esophagectomy with second- or third-field lymph node dissection. Postoperatively, patients were followed up every 3 months during the first 2 years and every 6 months thereafter.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObservational results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrimary endpoints included the induction-to-surgery conversion rate and the R0 resection rate. The conversion success rate was defined as the proportion of patients with cT3br deemed operable following induction therapy. R0 resection was defined as the microscopic absence of cancer cells at resection margins on pathological slides. Secondary endpoints included overall survival (OS), disease-free survival (DFS), pCR, radiological response rate, and safety. OS was defined as the time from surgery to death from any cause. DFS was the time from surgery to recurrence or death from any cause. pCR was defined as the absence of residual tumor cells in the resected primary tumor or regional lymph nodes. Post-treatment pathological classifications based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 included partial response (PR), progressive disease (PD), and stable disease (SD).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical characteristics were compared using the chi-square test, Fisher\u0026rsquo;s exact test, and student\u0026rsquo;s t-test. Data analysis was performed using SPSS software (version 29.0). Kaplan\u0026ndash;Meier survival analysis curves were used to assess PFS and OS, and the log-rank test was used to compared survival differences between the groups. Kaplan\u0026ndash;Meier survival curves were generated using R software (version 4.3.2). All statistical tests were two-tailed, with a \u003cem\u003eP\u003c/em\u003e value \u0026lt; 0.05 considered significant.\u003c/p\u003e"},{"header":"Result","content":"\u003cp\u003e\u003cstrong\u003eBaseline characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter NICT, 12 patients in the cT3br group were deemed unresectable. A total of 102 patients underwent radical surgery and were included in the analysis. The surgical conversion rate after NICT was 76.9% (40/52), with 62 and 40 patients in the cT3r and cT3br groups, respectively. Table 1 indicates no significant differences in baseline characteristics, such as age, sex, BMI, and clinical N stage, between the two groups. However, primary tumor locations differed significantly (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.025). In the cT3br group, the tumor was primarily located in the middle (85%) and upper esophagus (10%), while in the cT3r group, it was predominantly located in the middle (64.5%) and lower esophagus (25.8%). Radiological evaluations revealed no significant differences in treatment response between the groups (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.111). Table 1 shows that 41 patients (66.1%) in the cT3r group achieved a partial response (PR) after two cycles of NICT compared to 33 patients (82.5%) in the cT3br group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable. 1 Clinical characteristics of the patients of cT3r and cT3br\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003ecT3r (n=62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003ecT3br (n=40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eAge, mean \u0026plusmn; SD，year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e63.60 \u0026plusmn; 7.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e64.65 \u0026plusmn; 9.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0.520\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e49 (79.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e29 (72.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.480\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e13 (21.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e11 (27.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026le; 22.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e36 (58.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e29 (72.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.139\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e＞22.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e26 (41.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e11 (27.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eTumor location\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eUpper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e6 (9.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e4 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eMiddle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e40 (64.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e34 (85%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eLower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e16 (25.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e2 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eSuspected organ invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eAorta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e15 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 60px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eTrachea and bronchus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e29 (72.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003ePulmonary vein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e6 (15.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eChemotherapy regime\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eDocetaxel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e13 (21.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e20 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eNab-paclitaxel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e49 (79.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e20 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eImmunotherapy regime\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eCamrelizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e15 (24.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e10 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eSintilimab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e39 (62.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e26 (65.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eTislelizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e6 (9.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e3 (7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eToripalimab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e2 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1 (2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eClinical N stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eN0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e30 (48.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e14 (35.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.131\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eN1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e25 (40.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e24 (60.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eN2-3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;7 (11.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e2 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eClinical response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e41 (66.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e33 (82.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.111\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eSD/PD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e21 (33.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e7 (17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e＊PR, Partial Response；PD, Progression Disease；SD, Stale Disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurgical outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 summarizes surgical and postoperative pathological outcomes. Surgical duration was comparable between the cT3r and cT3br groups (208.5 minutes vs. 205.2 minutes, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.259). Intraoperative blood loss, number of lymph nodes dissected, and postoperative hospital stays were also comparable between the two groups (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026gt; 0.05). Tumors in the cT3br group had a significantly higher likelihood of \u0026nbsp;adjacent organs invasion than those in the cT3r group (20.0% vs. 9.7%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.02). Intraoperative and postoperative pathological findings revealed that in the cT3br group, 7 cases (11.3%) showed bronchial invasion, 1 case (2.5%) showed aortic invasion, and 1 case (2.5%) showed pericardial invasion. In the cT3r group, bronchial invasion was observed in 2 cases (3.2%), mediastinal pleura invasion in 2 cases (1.6%), and diaphragm, lung, and thoracic duct invasion in 1 case each (1.6%). The non-R0 resection rate was significantly higher in the cT3br group than in the cT3r group (20.0% vs. 3.2%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.005). No significant differences were observed between the two groups regarding the pCR rate or postoperative pathological staging (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.499 and \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.914, respectively). As shown in Table 3, pulmonary infection was the most common postoperative complication in both groups, although the difference was not statistically significant (cT3r, 22.6% vs. cT3b, 35%; \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.179). Similarly, there were no significant differences between the groups in terms of other complications, including anastomotic leakage, chylothorax, and respiratory failure (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable. 2 Surgical and pathological result between cT3r and cT3br\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003ecT3r (n=62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003ecT3br (n=40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eOperation time, median (range),min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e208.5 (190.2-235.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e205.2 (177.8-233.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.259\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eBlood loss, median (range), ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e80.0 (50.0-100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e100.0 (50.0-115.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.276\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eNo.of LNs harvested, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e21.10 \u0026plusmn; 9.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e20.08 \u0026plusmn; 9.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.590\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003ePOLS, median (range), days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e8.0 (7.0-9.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e9.0 (8.0-10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.210\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eResection margins\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eR0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e60（96.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e32（80.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eR1/2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e2（3.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e8（20.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003ePathological CR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003epCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e12（19.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e10（25.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.499\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eNon-pCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e50（80.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e30（75%）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003ePathological organ invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e56（90.3%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e32（80.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eDiaphragm/Thoracic Duct/Lung/Pleura\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e5（8.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e1 (2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eAorta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e1 (2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eTrachea and bronchus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e2（3.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e7 (11.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003ePulmonary vein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eypTNM stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e26 (41.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e19 (47.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.914\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e4 (6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e2 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eIIIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e8 (12.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e5 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eIIIB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e16 (25.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e5 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eIVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e8 (12.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e9 (22.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003ePostoperative adjuvant therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e27 (43.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e21 (52.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.377\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e35 (56.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e19 (47.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eRecurrence after surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e40 (64.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e30 (75.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.491\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eLoco-regional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e2 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eDistant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e15 (24.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e6(15.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eLoco-regional and Distant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e5 (8.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003e4 (10.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e＊LN, lymph node; POLS, Postoperative Length of Stay; pCR, Pathological complete response\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable. 3\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eComplications after surgical treatment.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003ecT3r (n=62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003ecT3br (n=40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003ePulmonary infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e14 (22.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e14 (35.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.170\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e48 (77.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e26 (65.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eAnastomotic leakage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e1 (1.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 59px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e61 (98.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e40 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eChylothorax\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 59px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e62 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e40 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eRespiratory failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1 (2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.392\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e62 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e39 (97.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eSurvival outcomes and recurrence patterns\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median follow-up duration was 30.5 months (95% CI, 23.98\u0026ndash;37.02). As shown in Fig. 3, the 3-year OS and DFS rates were 67% and 47% for the cT3r group, respectively, and 76% and 69% for the cT3br group, with no statistically significant differences (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.453; \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.155). Conversely, non-R0 resection was significantly associated with worse OS (3-year OS; R0 75% vs non-R0 16%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.001) and showed a near-significant trend in DFS (3-year DFS; R0 60% vs non-R0 29%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.069). This study also analyzed the postoperative failure patterns in the two groups. As shown in Table 2, 7 patients in the cT3r group experienced local recurrence, and 20 developed distant metastases; in the cT3br group, 4 cases of local recurrence and 10 cases of distant metastases were observed, with no statistically significant differences in recurrence rates (35.5% vs 25%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.491). Furthermore, the cT3br group received more aggressive adjuvant therapies than the cT3r group, although this difference was not statistically significant (52.5% vs 43.5%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.377).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study compared the surgical outcomes and survival prognoses of the patients with cT3r and cT3br esophageal squamous cell carcinoma following NICT. To the best of our knowledge, this is the first study to evaluate the treatment outcomes of these two groups under the NICT regimen. Two key findings emerged: (1) with the NICT regimen, the induction-to-surgery conversion rate for BR-ESCC was 76.9% (40/52). Due to the potential invasion into adjacent vital organs in the cT3br group, the non-R0 resection rate was significantly higher than in the cT3r group. (2) Despite higher malignancy in the cT3br group, treatment outcomes and survival prognoses were comparable to those of the cT3r group after surgery. These findings suggest that for patients with BR-ESCC, the primary treatment strategy should focus on selecting induction regimens that maximize surgical conversion rates and improve R0 resection rates.\u003c/p\u003e \u003cp\u003eLandmark studies, such as the CROSS and NEOCRTE5010, have established the pivotal role of NRCT in managing locally advanced ESCC.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e However, the optimal preoperative treatment strategy for BR-ESCC remains unclear due to its unique imaging and anatomical characteristics. NEOCRTEC-1601, a single-center phase II clinical trial evaluated surgical outcomes following docetaxel, cisplatin, and fluorouracil (TPF) chemotherapy for BR-ESCC.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e After 2\u0026ndash;3 cycles of TPF treatment, the study reported an induction-to-surgery conversion rate of 57.4% (27/47), with 25 patients (53.2%) achieving R0 resection and a 3-year OS rate of 54.4%. Similarly, TOMOYA et al.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e demonstrated that DCF triple-drug chemotherapy significantly improved surgical conversion rate (81.2% vs 71.4%) and R0 resection rates (62.5% vs 37.5%) compared to the FP regimen, without increasing surgical complications or toxicities apart from myelosuppression. Unlike simple induction chemotherapy regimens, several studies have assessed the efficacy of NRCT for the treatment of BR-ESCC. A Japanese retrospective study\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e showed that among 50 patients with BR-ESCC undergoing neoadjuvant chemoradiotherapy (NACRT), 27 (54%) successfully achieved induction conversion therapy, with an R0 resection rate of 81.4% (22/27). The study also identified elevated pre-NACRT serum SCC antigen levels as predictive of treatment failure and poor survival. However, we argue that NRCT may not be optimal for patients with BR-ESCC. As highlighted in our previous study, localized effects of radiotherapy can induce edema and fibrosis in the tumor region, complicating clinical staging. This inflammatory edema may hinder the short-term assessment of post-treatment resectability, leading to delayed interventions or missed surgical opportunities.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eImmune checkpoint inhibitors are emerging antitumor agents that primarily eradicate cancer cells by reactivating cytotoxic T cells.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e However, clinical data on the efficacy of immunotherapy for BR-ESCC remains relatively limited. A prospective single-center phase II study (ChiCTR2200056728) demonstrated\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e that preoperative camrelizumab combined with chemotherapy achieved a 71% induction-to-surgery conversion rate (22/31), with 81.8% of patients (18/22) undergoing R0 resection. Our findings align with these results. With a median follow-up of 30.5 months (95% CI, 23.98\u0026ndash;37.02), the cT3br group exhibited 3-year OS and DFS rates of 76% and 69%, respectively. Notably, despite the higher malignancy rate in the cT3br group, the cT3r group did not show a postoperative survival advantage (OS, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.453; DFS, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.155). This consistency with prior studies, including those by Ryosuke\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e and Akiyuki\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e on NRCT in BR-ESCC, may be attributed to the more aggressive adjuvant treatments administered to cT3br group patients at our center postoperatively. Nonetheless, this suggests that successful induction conversion surgery allows patients with BR-ESCC to achieve surgical outcomes and long-term survival comparable to those with cT3r. Additionally, since the cT3br group patients may exhibit potentially have invasion of adjacent vital organs, enhancing the R0 resection rate is particularly critical. This underscores the need for future research to further treatment strategies for BR-ESCC.\u003c/p\u003e \u003cp\u003eThis study had some limitations. Firstly, as a single-center retrospective study with limited sample size and heterogeneous chemotherapy and immunotherapy regimens, these findings require validation in large-scale, multicenter prospective studies. Second, there is no consensus on the diagnostic criteria for BR-ESCC. Although patient grouping in this study was performed using multidisciplinary evaluations, subjectivity and variability may have influenced the process. Finally, due to the limited baseline clinical data available, we could not analyze preoperative risk factors for non-R0 resection in surgical patients, which are crucial for developing effective treatment strategies for BR-ESCC.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, NICT appears to be an effective treatment strategy for BR-ESCC, providing high surgical conversion rates, favorable surgical outcomes, and long-term survival comparable to patients with cT3r. Future treatment strategies for BR-ESCC should prioritize improving surgical conversion success and enhancing R0 resection rates.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBR-ESCC Borderline resectable esophageal squamous cell carcinoma\u003c/p\u003e\n\u003cp\u003eNICT Neoadjuvant immunochemotherapy\u003c/p\u003e\n\u003cp\u003eOS Overall survival \u003c/p\u003e\n\u003cp\u003eDFS Disease-free survival\u003c/p\u003e\n\u003cp\u003eNRCT Neoadjuvant chemoradiotherapy\u003c/p\u003e\n\u003cp\u003eMDT Multidisciplinary treatment \u003c/p\u003e\n\u003cp\u003eCT Computed tomography\u003c/p\u003e\n\u003cp\u003ePR Partial response\u003c/p\u003e\n\u003cp\u003ePD Progressive disease \u003c/p\u003e\n\u003cp\u003eSD Stable disease\u003c/p\u003e\n\u003cp\u003epCR Pathological complete remission\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was reviewed and approved by the Ethics Committee of Affiliated Hospital of North Sichuan Medical College. According to national legislation and institutional requirements, written informed consent was not required for participation in this study. (File number: 2024ER743-1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Nanchong City University Science and Technology Strategic Cooperation Special Fund (Grant No. 22SXQT0095) and the Scientific Research Foundation for Advanced Talents, Affiliated Hospital of North Sichuan Medical College (Grant No. 2023GC006)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBX: Conceptualization, Data curation, Methodology, Writing - original draft, Writing - review \u0026amp; editing. CZ: Conceptualization, Investigation, Methodology, Writing - review \u0026amp; editing. TL: Data curation, Investigation, Methodology, Writing - review \u0026amp; editing. YZ: Data curation, Investigation, Methodology, Writing - review \u0026amp; editing. LZ: Data curation, Investigation, Methodology, Writing - review \u0026amp; editing. JL: Conceptualization, Methodology, Supervision, Writing - review \u0026amp; editing. GS: Conceptualization, Funding acquisition, Supervision, Writing - review \u0026amp; editing. MF: Conceptualization, Project administration, Supervision, Visualization, Writing - review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Editage (www.editage.cn) for English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNjei B, McCarty T R, Birk J W. Trends in esophageal cancer survival in United States adults from 1973 to 2009: a SEER database analysis. \u003cem\u003eJournal of Gastroenterology and Hepatology\u003c/em\u003e, 2016, 31(6): 1141-1146.\u003c/li\u003e\n\u003cli\u003eYang J, Liu X, Cao S, Dong X, Rao S, Cai. Understanding Esophageal Cancer: The Challenges and Opportunities for the Next Decade. \u003cem\u003eFrontiers in Oncology\u003c/em\u003e, 2020, 10: 1727.\u003c/li\u003e\n\u003cli\u003eYang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, et al. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. \u003cem\u003eJournal of Clinical Oncology\u003c/em\u003e, 2018, 36(27): 2796-2803.\u003c/li\u003e\n\u003cli\u003eVan Hagen P, Hulshof M C C M, Van Lanschot J J B, Steyerberg E W, Van Berge Henegouwen M I, Wijnhoven B P L, et al. 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Clinical outcomes of conversion surgery after induction immunochemotherapy for borderline resectable T4 esophageal squamous cell carcinoma. \u003cem\u003eWorld Journal of Surgical Oncology\u003c/em\u003e, 2024, 22(1): 288.\u003c/li\u003e\n\u003cli\u003eZhang G, Mu T, Zhang Y, Jiao J, Ding Z, Yang H, et al. Preoperative camrelizumab combined with chemotherapy for borderline resectable ESCC: a single-arm, prospective, phase 2 study. \u003cem\u003eMed (New York, N.Y.)\u003c/em\u003e, 2024, 5(11): 1424-1432.e3.\u003c/li\u003e\n\u003cli\u003eChao L, Liu J, Chen Y, Fan Y, Guo S, Zhang S. Benefits of camrelizumab plus carboplatin and albumin paclitaxel as induction therapy for locally advanced borderline resectable or unresectable esophageal squamous cell carcinoma. \u003cem\u003eThoracic Cancer\u003c/em\u003e, 2024, 15(8): 622-629.\u003c/li\u003e\n\u003cli\u003eEyck B M, Van Lanschot J J B, Hulshof M C C M, Van Der Wilk B J, Shapiro J, Van Hagen P, et al. Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial. \u003cem\u003eJournal of Clinical Oncology\u003c/em\u003e, 2021, 39(18): 1995-2004.\u003c/li\u003e\n\u003cli\u003eWu J D, Wang Z Q, Li Q Q, Li Z C, Ren C, Wang D S, et al. A 3-year survival update from a phase 2 study of paclitaxel plus cisplatin and 5-fuorouracil induction chemotherapy for locally advanced borderline-resectable esophageal squamous cell carcinoma: the NEOCRTEC-1601 clinical trial. \u003cem\u003eAnnals of Surgical Oncology\u003c/em\u003e, 2024, 31(2): 838-846.\u003c/li\u003e\n\u003cli\u003eYokota T, Hatooka S, Ura T, Abe T, Takahari D, Shitara K, et al. Docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy for locally advanced borderline-resectable T4 esophageal cancer. \u003cem\u003eAnticancer Research\u003c/em\u003e, 2011, 31(10): 3535-3541.\u003c/li\u003e\n\u003cli\u003eSuzuki T, Okamura A, Watanabe M, Mine S, Imamura Y, Asari T, et al. Neoadjuvant Chemoradiotherapy with Cisplatin Plus Fluorouracil for Borderline Resectable Esophageal Squamous Cell Carcinoma. \u003cem\u003eAnnals of Surgical Oncology\u003c/em\u003e, 2020, 27(5): 1510-1517.\u003c/li\u003e\n\u003cli\u003eHan D, Li B, Zhao Q, Sun H, Dong J, Hao S, et al. The key clinical questions of neoadjuvant chemoradiotherapy for resectable esophageal cancer\u0026mdash;a review. \u003cem\u003eFrontiers in Oncology\u003c/em\u003e, 2022, 12: 890688.\u003c/li\u003e\n\u003cli\u003eZhang J, Dang F, Ren J, Wei W. Biochemical aspects of PD-L1 regulation in cancer immunotherapy. \u003cem\u003eTrends in Biochemical Sciences\u003c/em\u003e, 2018, 43(12): 1014-1032.\u003c/li\u003e\n\u003cli\u003eSalas-Benito D, P\u0026eacute;rez-Gracia J L, Ponz-Sarvis\u0026eacute; M, Rodriguez-Ruiz M E, Mart\u0026iacute;nez-Forero I, Castaňόn E, et al. Paradigms on Immunotherapy Combinations with Chemotherapy. \u003cem\u003eCancer Discovery\u003c/em\u003e, 2021, 11(6): 1353-1367.\u003c/li\u003e\n\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":"borderline resectable, esophageal squamous cell carcinoma，neoadjuvant immunochemotherapy，neoadjuvant chemoradiotherapy，R0 resection, surgical outcomes","lastPublishedDoi":"10.21203/rs.3.rs-6786605/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6786605/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Immune checkpoint inhibitors have demonstrated preliminary safety and efficacy in treating borderline resectable esophageal squamous cell carcinoma (BR-ESCC). We aimed to compare treatment and survival outcomes between patients with locally advanced resectable ESCC (cT3r) and those with borderline resectable ESCC (cT3br) who underwent surgery following neoadjuvant immunochemotherapy (NICT).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: After NICT, 12 patients in the cT3br group were deemed unresectable, while 102 patients with clinically staged T3 ESCC underwent surgery and were included in the study. Patients were categorized into cT3r and cT3br groups based on the likelihood of adjacent vital organ invasion as observed on pre-treatment CT scans.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Among the participants, 52 patients were included in the cT3br group and 62 in the cT3r group. The surgical conversion rate for cT3br tumors was 76.9% (40/52). Both groups exhibited comparable outcomes in terms of surgical treatment and postoperative complications (\u003cem\u003eP \u003c/em\u003e\u0026gt; 0.05). Although the non-R0 resection rate was significantly higher in the cT3br group than in the cT3r group (20.0% vs 3.2%, \u003cem\u003eP \u003c/em\u003e= 0.005), no significant differences were observed in postoperative overall survival (OS) or disease-free survival (DFS) between the two groups (3-year OS: 76% vs 67%, \u003cem\u003eP \u003c/em\u003e= 0.453; 3-year DFS: 69% vs 47%, \u003cem\u003eP \u003c/em\u003e= 0.155). Non-R0 resection was significantly associated with worse OS (\u003cem\u003eP \u003c/em\u003e= 0.001) and showed a trend toward association with DFS (\u003cem\u003eP \u003c/em\u003e= 0.069).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Surgery following NICT is an effective treatment strategy for BR-ESCC, achieving treatment outcomes and survival prognoses comparable to those in patients with cT3r.\u003c/p\u003e","manuscriptTitle":"Effective surgical conversion after neoadjuvant immunochemotherapy improves clinical outcomes in borderline resectable esophageal cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-17 14:45:39","doi":"10.21203/rs.3.rs-6786605/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":"c193b3ca-7f6a-4281-9613-e99d2ffaf23b","owner":[],"postedDate":"June 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-22T16:53:35+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-17 14:45:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6786605","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6786605","identity":"rs-6786605","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}