Prognostic Impact of Supraclavicular Lymph Node Metastasis in Thoracic Oesophageal Squamous Cell Carcinoma in a Large Retrospective Study

Prognostic Impact of Supraclavicular Lymph Node Metastasis in Thoracic Oesophageal Squamous Cell Carcinoma in a Large Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prognostic Impact of Supraclavicular Lymph Node Metastasis in Thoracic Oesophageal Squamous Cell Carcinoma in a Large Retrospective Study Pengqiang Gao, Junpeng Lin, Xiaofeng Chen, Peiyuan Wang, Hui Lin, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9406877/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract The definitions of regional nodes differ between the 12th edition of the JES and the UICC staging systems, and the most prominent difference is in the status of the supraclavicular lymph nodes (SCLN). This study was designed to investigate the prognostic impact of metastasis to SCLN in patients with thoracic oesophageal squamous cell carcinoma (ESCC). The study group consisted of 1639 patients with thoracic ESCC who underwent oesophagectomy with 3-field lymphadenectomy at the Department of Thoracic Surgery, Fujian Cancer Hospital and whose clinical and survival information were collected.Of the 1639 patients, 668 (40.8%) had no lymph node metastases, 805 (49.1%) had at least 1 positive node but were SCLN-negative, and 166 (10.1%) had SCLN metastases. The 5-year survival rate was 74.1% for node-negative patients, 44.3% for node-positive patients without SCLN metastases, and 33.7% for patients with SCLN metastases. A comparison of the 5-year survival rates among patients with SCLN metastases revealed that the SCLN-positive group was more similar to the N2 group (P = 0.342) than to the N3 group (P = 0.027). In the multivariate analysis, the male sex (P < 0.001), a higher pT stage (P = 0.005), a poorer degree of pathological differentiation (P = 0.045), and a higher N stage (P < 0.001) retained statistical significance as adverse prognostic factors for overall survival, while SCLN metastasis did not (P = 0.956). The survival benefit of 3-field lymphadenectomy including metastases to SCLNs was indicated in patients with thoracic ESCC. SCLNs appear to be regional nodes similar to other regional nodes. Oesophageal carcinoma Oesophagectomy Supraclavicular lymph nodes Survival rate Prognosis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 INTRODUCTION Oesophageal carcinoma is the tenth most common cancer in the world and ranks sixth in China.[ 1 ][ 2 ] Oesophageal squamous cell carcinoma (ESCC) is the most common histologic cell type in eastern Asian countries and is very invasive, spreading to regional and distant lymph nodes (LNs) at a relatively early stage.[ 3 ] The 3-field lymphadenectomy has long been performed in several Asian countries, including China, the level of LN metastasis can be accurately determined via surgery. More than half of advanced oesophageal carcinoma patients are diagnosed with LN metastasis, and the presence of LNs metastatic is a significant poor prognostic factor in patients with oesophageal cancer.[ 3 ] Therefore, standard lymph node dissection is essential to improve the prognosis of patients with oesophageal cancer. However, there is still controversy between East and West on whether to perform supraclavicular lymph node dissection for thoracic oesophageal cancer.[ 4 ] However, the definitions of regional nodes differ between the Japan Oesophageal Society (JES) classification system and the Union for International Cancer Control (UICC) staging system. The most prominent difference is in the status of the supraclavicular lymph nodes (SCLNs), which have been regarded as regional LNs in Japan and other eastern Asian countries and distant LNs in Western countries.[ 5 ][ 6 ] In 2023, the JES updated its oesophageal cancer practice guidelines. In the 12th edition of the JES staging system, for the first time, the classification of the LN groups by site of origin was no longer used for thoracic oesophageal cancer, and a new unified regional LN classification was established for thoracic oesophageal cancer. In addition, SCLNs were categorized as distant LNs instead of regional LNs. [ 7 ][ 8 ] However, there is still a lack of bulk studies to confirm the current update for the guidelines. Therefore, the study aims to analyse the prognostic impact of SCLN metastatic status on ESCC patients based on a single-centre bulk data, as well as to investigate whether SCLN should be regarded as a regional lymph node in thoracic oesophageal squamous carcinoma. The conventional strategy for dissection is based on the hypothesis that thoracic oesophageal tumour cells involve nearby periesophageal nodes first, while mid- and lower oesophageal tumours involve mid- and lower periesophageal nodes first. Then, tumour cells spread to slightly farther nodes in the upper mediastinum and perigastric area. Finally, tumour cells reach distant nodes in the supraclavicular and celiac areas.[ 9 ] An anatomical study by Kuge et al. showed that long longitudinal lymphatic extension in the oesophageal submucosa is very evident.[ 10 ] Another anatomical study showed a morphological connection between submucosal lymphatic vessels in the proximal oesophagus and recurrent nerve nodes in the superior mediastinum.[ 11 ] These morphologies suggest an explanation for anatomically distant LN metastasis known as 'skip metastasis' in thoracic oesophageal cancer. Kuge et al. also reported that lymphatic routes to periesophageal LNs usually originate from the intermuscular area of the muscularis propria and that lymphatic communication between the submucosa and intermuscular area is rarely apparent histologically.[ 12 ] However, the prognostic impact of these LN metastases from ESCC remains divisive.[ 13 ] In this study, we sought to investigate the prognostic impact of metastatic disease in the SCLNs of patients with ESCC and whether SCLNs should be considered regional LNs in these patients. MATERIALS AND METHODS A total of 1908 patients with thoracic oesophageal cancer underwent surgery from 1999 to 2009, at the Department of Thoracic Surgery, Fujian Cancer Hospital, Fujian Medical University Attached Cancer Hospital. All patient data, including demographic characteristics, symptoms, clinical stage, treatment features, and survival information, were collected. Surgical features, pathologic stage, and detailed LN metastatic status were also collected for the patients who underwent surgery. Of the 1908 patients who underwent oesophagectomy including 3-field lymphadenectomy for R0 resection, 1812 had postoperative histopathological findings of squamous carcinoma and did not receive neoadjuvant therapy. Thus, the total study group comprised 1639 patients with histologically confirmed ESCC who underwent R0 resection and 3-field oesophagectomy without neoadjuvant therapy. The pathologic stage for all patients was reassessed according to the 8th edition of the UICC TNM classification system, and the clinical stage determined using the 8th edition of the UICC/American Joint Committee on Cancer TNM staging system was available for all patients treated. The TNM classification divides the intrathoracic oesophagus into the following 3 anatomic subsites: upper, middle, and lower.[ 14 ] SCLN metastasis was defined by LNs with pathologically confirmed metastasis situated between the inferior belly of the omohyoid muscle posteriorly and the clavicle/upper border of the manubrium anteriorly but also inferior to the lower margin of the cricoid.[ 15 ] Statistical methods Statistical analysis was performed, and relevant curves were created using SPSS 23.0. Unless otherwise stated, mean values and standard deviations are reported. Student's t test was used for comparisons between subgroups. For categorical variables, the chi-square test or Fisher's exact test was used, as appropriate. The kappa test was used to evaluate the consistency between clinical stage and pathologic stage. Survival curves were constructed using the Kaplan–Meier method, which was also used for univariate analysis. Variables with a P value less than 0.1 were included in the Cox proportional hazards model. RESULTS 1. Clinical pathological data The characteristics of the 1639 patients enrolled in this study are listed in Table 1 . The median age of the patients was 56 years. Postoperative pathology revealed that more than half of the patients (75.3%) had proven T3-T4. The tumour location was the upper oesophagus in 265 patients (16.2%), the middle oesophagus in 1240 patients (75.7%), and the lower oesophagus in 134 patients (8.2%). There were 668 patients without LN metastases (40.8%) and 971 patients with LN metastases (59.2%). Of the 971 patients with LN involvement, 805 patients (49.1%) had at least 1 positive LN but were SCLN-negative, and 166 patients (10.1%) had SCLN metastasis. According to the tumour location, the frequency of SCLN metastasis was 14.0% in patients with upper oesophageal tumours, 9.5% in patients with middle oesophageal tumours, and 8.2% in patients with lower oesophageal tumours. The median number of resected nodes was 24.44 (range 1 ~ 74) in this study. Table 1 Patients’ characteristics and tumor data Characteristic and finding No. (%) Median age (range), y 56(30–82) Sex Male 1231(75.1) Female 408(24.9) Tumor location Upper 265(16.2) Middle 1240(75.7) Lower 134(8.2) Degree of pathological differentiation Well-differentiated 280(17.0) Moderately-differentiated 1085(66.2) Poorly-differentiated 274(16.7) Pathologic T classification T1 137(8.4) T2 268(16.4) T3 968(59.1) T4 266(16.2) Pathologic positive node no. (including supraclavicular node) N0 668(40.8) N(1–2) 471(28.7) N(3–6) 346(21.1) N(7-) 154(9.4) Pathologic M classification M1 (supraclavicular node) 166(10.1) 2. Survival analysis The median overall survival (OS) across all patients was 50.20 months, and the 5-year survival rate was 55.4%. The 5-year survival rate was 74.1% for patients with N0, 44.3% for node-positive patients without SCLN disease, and 33.7% for node-positive patients with SCLN metastasis (Fig. 1 ); these differences between pN (+) SCLN(-) and pN (+) SCLN(+) were significant (P < 0.001). Among those patients without SCLN metastasis, the 5-year survival rate was 46.7% for patients with 1–2 positive LNs (pN1), 43.9% for patients with 3–6 positive LNs (pN2), and 18.6% for patients with more than 7 positive LNs (pN3). The 5-year survival rate in the SCLN-positive group was more similar to that in the N2 group (P = 0.342) than that in the N3 group (P = 0.027) (Fig. 2 ). According to the univariate analysis of survival (Table 2 ), the male sex (P < 0.001), poorer degree of pathological differentiation (P < 0.001), a higher T stage (P < 0.001), a higher N stage (P < 0.001), and metastasis to SCLNs (P = 0.020) were associated with worse 5-year OS. Table 2 Univariate analysis of factors for survival Factor 5-y Survival (%) HR P value Sex < 0.001 Male 52.0 1.555 Female 65.7 Tumor location 0.806 Upper 54.7 Middle 55.6 0.950 Lower 55.2 0.906 Degree of pathological differentiation < 0.001 Well-differentiated 64.6 Moderately-differentiated 54.5 1.449 Poorly-differentiated 49.6 1.649 Pathologic T classification < 0.001 T1 81.8 T2 59.7 2.397 T3 55.5 2.852 T4 37.2 5.221 Pathologic N classification (including supraclavicular node) 0) 0.020 Negative 44.3 Positive 33.7 1.281 N(1–2) 46.7 N(3–6) 43.9 N(7-) 18.6 3. Stratified analysis based on location Among patients with upper thoracic oesophageal tumours, the 5-year survival rate was 69.1% for lymph node negative patients, 42.4% for lymph node positive patients without SCLN metastasis, and 51.4% for patients with SCLN metastasis (Fig. 3 A). The difference between the pN(+)SCLN(-) group and the pN(+)SCLN(+) group was not significant (p = 0.562). Among patients with middle thoracic oesophageal tumours, the 5-year survival rate was 74.6% for lymph node negative patients, 44.6% for lymph node positive patients without SCLN metastasis, and 28.8% for patients with SCLN metastasis (Fig. 3 B). The difference between the pN(+)SCLN(-) group and the pN(+)SCLN(+) group was significant (p = 0.004). Among patients with lower thoracic oesophageal tumours, the 5-year survival rate was 81.0% for lymph node negative patients, 45.7% for lymph node positive patients without SCLN metastasis, and 27.3% for patients with SCLN metastasis (Fig. 3 C). The difference between the pN(+)SCLN(-) group and the pN(+)SCLN(+) group was not significant (p = 0.807). According to the analysis of the number of involved LNs, including the SCLNs, patients with more positive nodes showed significantly worse survival (Fig. 4 ). 4. Multivariate analysis A multivariate analysis was performed using factors that were significant in the univariate analysis. Table 3 shows that the male sex (P = 0.001), poorer degree of pathological differentiation (P = 0.045), a higher T stage (P = 0.005), and more positive nodes (P < 0.001) retained statistical significance as adverse prognostic factors for OS, while SCLN metastasis did not (P = 0.956). As shown in Fig. 5 A, 5 B, and 5 C, in patients with the same number of positive nodes, the SCLN status did not predict survival outcomes. Although the 5-year OS was worse in patients with SCLN metastases, this may be related to other confounding factors including T-stage and N-stage rather than SCLN status. Table 3 Multivariate analysis of factors for survival Factor Risk ratio 95%CI P value Sex Male/Female 1.368 1.136–1.648 0.001 Degree of pathological differentiation Moderately,Poorly-differentiated/Well-differentiated 1.246 1.005–1.546 0.045 T stage T3,T4/T0,T1,T2 1.323 1.091–1.605 0.005 No. of positive nodes including supraclavicular nodes N(1–2)/N0 2.123 1.737–2.595 <0.001 N(3–6)/N0 2.956 2.391–3.655 <0.001 N(7-)/N0 4.745 3.654–6.161 <0.001 Supraclavicular node Positive/negative 1.006 0.804–1.259 0.956 DISCUSSION The accurate staging of oesophageal cancer is essential for predicting patient prognosis, as different stages provide critical guidance for assessing outcomes and informing treatment decisions. The current staging systems for oesophageal cancer primarily include the primary tumor (T stage), lymph node metastasis (N stage), and distant metastasis (M stage), with the N stage being a key component of the system. Adequate lymph node dissection facilitates a more precise N stage evaluation. While 3-field lymphadenectomy provides comprehensive nodal staging and potential survival benefits in thoracic ESCC, its associated complications warrant careful consideration. Mine et al.[ 4 ] noted increased operative time and mortality with prophylactic SCLN dissection. Patient selection and targeted dissection are critical to balance efficacy and safety. However, differences persist between Eastern and Western approaches to lymph node dissection in oesophageal cancer, particularly regarding the necessity of supraclavicular lymph node (SCLN) dissection. The AJCC consistently classifies SCLN as distant metastasis. In the 7th edition of the international oesophageal cancer staging system published in 2009, the M1 subgroup (M1a and M1b) was eliminated, and SCLN metastasis was defined as distant metastasis. Rice et al. [ 16 ] analyzed 480 postoperative oesophageal cancer patients and found a significant survival difference between patients with M0 and M1 stages. However, no survival differences were observed between the M1a and M1b stages, prompting recommendations to eliminate the M1 subgroup. Similarly, Wijnhoven et al. [ 17 ] reported comparable 5-year survival rates between M1a and M1b patients, supporting this perspective. The AJCC's classification of SCLN as an M stage is based on its biological characteristics as distant metastasis and its influence on prognosis. The evidence for the AJCC 8th edition staging system was derived from the WEC database, which focuses solely on the number of positive lymph nodes without considering their anatomical location [ 18 ]. Conversely, the JES staging system for abdominal lymph nodes adopts the Japanese gastric cancer staging, with specific modifications for mediastinal and cervical lymph nodes tailored to oesophageal cancer, supported by extensive research on lymph node metastasis locations in Japan [ 19 ]. Chang et al. [ 20 ] used propensity score matching analysis to compare the prognostic accuracy of the JES 11th edition and AJCC 8th edition systems in patients with thoracic oesophageal squamous cell carcinoma (ESCC). Their findings showed the AJCC 8th edition outperformed the JES 11th edition in predicting prognosis. Zhang et al. [ 21 ] compared the two systems in Chinese ESCC patients, concluding that both had similar prognostic performance. In earlier JES editions, SCLN was classified as a regional lymph node: a second station for upper and middle thoracic oesophageal cancer and a third station for lower thoracic oesophageal cancer. However, there remains controversy over the benefits of SCLN dissection. In the 12th edition of the JES staging system, SCLN was redefined as an extraregional lymph node (M1a stage)[ 7 ][ 8 ]. Some clinical studies indicate that the prognosis of SCLN metastasis is better than that of visceral metastasis. For example, Shim et al. [ 22 ] reported higher survival rates in patients with SCLN metastasis than in those with visceral organ metastasis, while Chao et al. [ 23 ] observed significantly improved survival rates in patients with SCLN metastasis after chemoradiotherapy compared to those with visceral metastasis. In summary, the classification of SCLN in thoracic oesophageal cancer remains contentious between Eastern and Western perspectives. Further large-scale studies are needed to clarify whether SCLN should be considered a regional lymph node. In this study, we analyzed 1,639 patients with ESCC who underwent 3-field lymphadenectomy. While patients with SCLN metastasis had significantly worse prognoses than those without SCLN metastasis, SCLN metastasis was not identified as an independent prognostic factor. Therefore, SCLN should be included as part of regional lymph node dissection in ESCC. The metastasis rate to SCLN in this study was 10.1%, consistent with previous reports of approximately 10% [ 3 ][ 14 ]. The mean number of dissected lymph nodes ranged from 1 to 74, with an average of 24.44 nodes. Among patients with SCLN metastasis, the mean number of dissected lymph nodes was 27.31. The SCLN metastasis rate varied depending on the tumor's location: Tachimori et al. [ 15 ][ 24 ] reported rates of 6.3–21.2% for upper thoracic tumors, 6.9–25.5% for middle thoracic tumors, and 3.7–6.2% for lower thoracic tumors. Similarly, our study found rates of 14.0%, 9.5%, and 8.2% for upper, middle, and lower thoracic tumors, respectively. These findings confirm the risk of SCLN metastasis regardless of the tumor's primary location. Survival analysis revealed that the pN (+) SCLN(-) group had better outcomes than the pN (+) SCLN(+) group. Univariate analysis confirmed that SCLN metastasis is closely associated with ESCC prognosis. However, stratified analysis by N stage showed no significant difference in 5-year survival rates between patients with and without SCLN metastasis within the same N stage. This suggests that SCLN behaves more like a regional lymph node, consistent with studies by domestic and Japanese researchers [[ 25 ][ 26 ][ 27 ]. Some studies argue that for middle and upper thoracic ESCC, SCLN should be considered a regional lymph node rather than distant metastasis [[ 24 ][ 25 ][ 28 ]. Subgroup analyses by tumor location in this study showed that among upper and lower thoracic patients, the survival rates of the pN (+) SCLN(-) group and pN (+) SCLN(+) group were comparable. However, for middle thoracic patients, the pN (+) SCLN(-) group had significantly better survival rates than the pN (+) SCLN(+) group. Further studies with larger sample sizes are required to confirm the impact of SCLN metastasis on prognosis in lower thoracic cases. Further multivariate analyses were performed and found that only the number of LNs, gender (male) and higher T-stage were found to be independent risk factors for survival outcomes, while SCLN metastasis was not an independent risk factor for prognosis in patients with oesophageal squamous carcinoma. Therefore, SCLN should be classified as part of the regional lymph nodes of oesophageal squamous carcinoma. In this study, we found that the prognosis of the SCLN metastasis group was similar to that of the pN2 stage and significantly superior to that of the pN3 stage. The similarity in survival between SCLN-positive (33.7%) and N2 patients (43.9%, P = 0.342) is driven by nodal burden, not anatomical location. Multivariate analysis confirmed that survival disparities are explained by N-stage (P < 0.001), not SCLN status (P = 0.956). This aligns with studies showing nodal quantity, not station, dictates prognosis in ESCC [ 26 ]. Therefore, we suggest that SCLN metastasis could be considered as part of N2 staging in subsequent staging updates to improve the accuracy of staging. While our study primarily focused on the prognostic role of SCLN metastasis in the era of surgical resection, recent advancements in systemic therapies, particularly immunotherapy, have reshaped the landscape of esophageal cancer management. Immune checkpoint inhibitors have demonstrated efficacy in both locally advanced and metastatic ESCC, with potential implications for lymph node metastasis control. For instance, the KEYNOTE-181 trial reported that pembrolizumab significantly improved overall survival in patients with advanced ESCC, including those with lymph node involvement.[ 29 ] Similarly, the CheckMate 577 trial highlighted the role of adjuvant nivolumab in reducing recurrence risk post-surgery, which may indirectly influence the management of regional nodes such as SCLNs.[ 30 ] Emerging evidence also suggests that immunotherapy could enhance the therapeutic effect of lymphadenectomy by targeting micrometastases. A recent multicenter study by Li et al. observed that neoadjuvant PD-1 blockade combined with chemotherapy resulted in higher pathological complete response rates in lymph nodes compared to chemotherapy alone.[ 31 ] These findings raise the possibility that future staging systems may need to account for the synergistic effects of immunotherapy and surgery, potentially redefining the prognostic significance of SCLN metastasis. However, our study's cohort predates the widespread use of immunotherapy, and further prospective studies are warranted to validate its impact on SCLN classification. As a large retrospective study containing data on 3-field lymphadenectomy in 1,639 cases of oesophageal squamous carcinoma, this study provides an important evidence-based basis for the clinical management of oesophageal cancer. Of course, this study has some limitations. First, the retrospective study design is an important limitation of this study. Retrospective studies usually rely on existing medical records, which may limit the completeness and accuracy of the data. In addition, retrospective studies are subject to selection bias. Second, the study was included over a relatively long period of time, and changes have occurred in the treatment methods and perioperative management of oesophageal cancer in the last few years, which can have an impact on the prognosis of patients. Finally, being a single-centre study, there is still a need to include more centres in the future to expand the sample size to validate the findings of this study. We will continue our efforts to improve the quality and applicability of the study and look forward to future studies that will provide more accurate and comprehensive results. The study suggests that SCLN should be considered part of regional lymph nodes in ESCC and proposes incorporating SCLN metastasis into the N2 stage for improved staging accuracy and patient outcomes, though further validation through prospective multi-center studies is warranted. Declarations Funding Information : The authors did not receive support from any organization for the submitted work. No funding was received to assist with the preparation of this manuscript. No funding was received for conducting this study. No funds, grants, or other support was received. The authors have no relevant financial or non-financial interests to disclose.All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Conflict of Interest : The authors have no conflict of interest.The authors have no competing interests to declare that are relevant to the content of this article. Ethics Statement : Approval of the research protocol by an Institutional Reviewer Board: K2024-063-01 Informed Consent: N/A Registry and the Registration No. of the study/trial: N/A Animal Studies: N/A Author Contributions : Pengqiang Gao and Junpeng Lin contributed equally to this work. Feng Wang conceived and designed the study. Pengqiang Gao, Junpeng Lin, Xiaofeng Chen, Peiyuan Wang, Hui Lin, Hang Zhou, Shuoyan Liu, and Feng Wang contributed to data collection, analysis, and interpretation. Pengqiang Gao and Junpeng Lin drafted the manuscript. All authors reviewed, edited, and approved the final version of the manuscript. Ethics approval and consent to participate This study was performed in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments. The study protocol was approved by the Ethics Committee of Fujian Cancer Hospital (Approval No. K2024-444-01). As this was a retrospective analysis of de-identified existing data, the committee granted a waiver of informed consent. Consent to participate : This retrospective study was approved by the Institutional Review Board of Fujian Cancer Hospital (Approval No. K2024-444-01). Due to the retrospective nature of the study and the use of anonymized data, the requirement for informed consent was waived by the ethics committee. Consent to publish : Not applicable. Competing interests :The authors declare no competing interests. Data Availability :The datasets generated and/or analysed during the current study are not publicly available due to patient privacy and confidentiality reasons but are available from the corresponding author on reasonable request. References Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71 (3):209-249. doi:10.3322/caac.21660. Zheng R, Zhang S, Zeng H, et al. Cancer incidence and mortality in China, 2016. J Natl Cancer Cent. 2022;2 (1):1-9. Published 2022 Feb 27. doi:10.1016/j.jncc.2022.02.002. Miyata H, Yamasaki M, Miyazaki Y, et al. Clinical Importance of Supraclavicular Lymph Node Metastasis After Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma. Ann Surg. 2015;262 (2):280-285. doi:10.1097/SLA.0000000000000933. Mine S, Watanabe M, Kumagai K, et al. 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Oncotarget. 2017;8 (25):41563-41571. doi:10.18632/oncotarget.14892. Yamasaki M, Miyata H, Miyazaki Y, et al. Evaluation of the nodal status in the 7th edition of the UICC-TNM classification for esophageal squamous cell carcinoma: proposed modifications for improved survival stratification: impact of lymph node metastases on overall survival after esophagectomy. Ann Surg Oncol. 2014;21 (9):2850-2856. doi:10.1245/s10434-014-3696-4. Tachimori Y, Ozawa S, Numasaki H, et al. Supraclavicular node metastasis from thoracic esophageal carcinoma: A surgical series from a Japanese multi-institutional nationwide registry of esophageal cancer. J Thorac Cardiovasc Surg. 2014;148 (4):1224-1229. doi:10.1016/j.jtcvs.2014.02.008. Udagawa H, Ueno M, Shinohara H, et al. The importance of grouping of lymph node stations and rationale of three-field lymphoadenectomy for thoracic esophageal cancer. J Surg Oncol. 2012;106 (6):742-747. doi:10.1002/jso.23122. Kojima T, Shah MA, Muro K, et al. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020;38 (35):4138-4148. doi:10.1200/JCO.20.01888 Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021;384 (13):1191-1203. doi:10.1056/NEJMoa2032125 Liu J, Yang Y, Liu Z, et al. Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma. J Immunother Cancer. 2022;10 (3): e004291. doi:10.1136/jitc-2021-004291 Additional Declarations No competing interests reported. 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08:17:41","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":43415,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9406877/v1/ab512deb75ac20df3aaead4c.jpg"},{"id":109760155,"identity":"e5b7720f-1a5a-40fc-a109-62c082dcb787","added_by":"auto","created_at":"2026-05-22 07:28:13","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":52011,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9406877/v1/21d71676d041b89075dab626.jpg"},{"id":109759711,"identity":"d544db97-1a75-4783-b1f2-a5aaf93fbd98","added_by":"auto","created_at":"2026-05-22 07:27:34","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":90660,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9406877/v1/f0b57ad73093c785fa789d02.jpg"},{"id":109760060,"identity":"a24b2108-d6ae-4f7d-a5e6-0286c91e5cdd","added_by":"auto","created_at":"2026-05-22 07:28:07","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":53786,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9406877/v1/0aaffb880280b3f07b2c5e38.jpg"},{"id":109446064,"identity":"9988fee6-16c4-4326-a44d-6cb2d118e7b1","added_by":"auto","created_at":"2026-05-18 08:17:41","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":94876,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9406877/v1/5e661e04dd0565b38486ee96.jpg"},{"id":109763827,"identity":"dc44ea2c-0429-475c-83ab-f7f4fe9a4aac","added_by":"auto","created_at":"2026-05-22 07:35:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":603015,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9406877/v1/05d28917-0290-4d45-8286-5ce25949d015.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic Impact of Supraclavicular Lymph Node Metastasis in Thoracic Oesophageal Squamous Cell Carcinoma in a Large Retrospective Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eOesophageal carcinoma is the tenth most common cancer in the world and ranks sixth in China.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e][\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Oesophageal squamous cell carcinoma (ESCC) is the most common histologic cell type in eastern Asian countries and is very invasive, spreading to regional and distant lymph nodes (LNs) at a relatively early stage.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] The 3-field lymphadenectomy has long been performed in several Asian countries, including China, the level of LN metastasis can be accurately determined via surgery. More than half of advanced oesophageal carcinoma patients are diagnosed with LN metastasis, and the presence of LNs metastatic is a significant poor prognostic factor in patients with oesophageal cancer.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Therefore, standard lymph node dissection is essential to improve the prognosis of patients with oesophageal cancer. However, there is still controversy between East and West on whether to perform supraclavicular lymph node dissection for thoracic oesophageal cancer.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eHowever, the definitions of regional nodes differ between the Japan Oesophageal Society (JES) classification system and the Union for International Cancer Control (UICC) staging system. The most prominent difference is in the status of the supraclavicular lymph nodes (SCLNs), which have been regarded as regional LNs in Japan and other eastern Asian countries and distant LNs in Western countries.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e][\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] In 2023, the JES updated its oesophageal cancer practice guidelines. In the 12th edition of the JES staging system, for the first time, the classification of the LN groups by site of origin was no longer used for thoracic oesophageal cancer, and a new unified regional LN classification was established for thoracic oesophageal cancer. In addition, SCLNs were categorized as distant LNs instead of regional LNs. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e][\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] However, there is still a lack of bulk studies to confirm the current update for the guidelines. Therefore, the study aims to analyse the prognostic impact of SCLN metastatic status on ESCC patients based on a single-centre bulk data, as well as to investigate whether SCLN should be regarded as a regional lymph node in thoracic oesophageal squamous carcinoma.\u003c/p\u003e \u003cp\u003eThe conventional strategy for dissection is based on the hypothesis that thoracic oesophageal tumour cells involve nearby periesophageal nodes first, while mid- and lower oesophageal tumours involve mid- and lower periesophageal nodes first. Then, tumour cells spread to slightly farther nodes in the upper mediastinum and perigastric area. Finally, tumour cells reach distant nodes in the supraclavicular and celiac areas.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAn anatomical study by Kuge et al. showed that long longitudinal lymphatic extension in the oesophageal submucosa is very evident.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Another anatomical study showed a morphological connection between submucosal lymphatic vessels in the proximal oesophagus and recurrent nerve nodes in the superior mediastinum.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] These morphologies suggest an explanation for anatomically distant LN metastasis known as 'skip metastasis' in thoracic oesophageal cancer. Kuge et al. also reported that lymphatic routes to periesophageal LNs usually originate from the intermuscular area of the muscularis propria and that lymphatic communication between the submucosa and intermuscular area is rarely apparent histologically.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] However, the prognostic impact of these LN metastases from ESCC remains divisive.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] In this study, we sought to investigate the prognostic impact of metastatic disease in the SCLNs of patients with ESCC and whether SCLNs should be considered regional LNs in these patients.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eA total of 1908 patients with thoracic oesophageal cancer underwent surgery from 1999 to 2009, at the Department of Thoracic Surgery, Fujian Cancer Hospital, Fujian Medical University Attached Cancer Hospital. All patient data, including demographic characteristics, symptoms, clinical stage, treatment features, and survival information, were collected. Surgical features, pathologic stage, and detailed LN metastatic status were also collected for the patients who underwent surgery. Of the 1908 patients who underwent oesophagectomy including 3-field lymphadenectomy for R0 resection, 1812 had postoperative histopathological findings of squamous carcinoma and did not receive neoadjuvant therapy. Thus, the total study group comprised 1639 patients with histologically confirmed ESCC who underwent R0 resection and 3-field oesophagectomy without neoadjuvant therapy.\u003c/p\u003e \u003cp\u003e The pathologic stage for all patients was reassessed according to the 8th edition of the UICC TNM classification system, and the clinical stage determined using the 8th edition of the UICC/American Joint Committee on Cancer TNM staging system was available for all patients treated. The TNM classification divides the intrathoracic oesophagus into the following 3 anatomic subsites: upper, middle, and lower.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eSCLN metastasis was defined by LNs with pathologically confirmed metastasis situated between the inferior belly of the omohyoid muscle posteriorly and the clavicle/upper border of the manubrium anteriorly but also inferior to the lower margin of the cricoid.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical methods\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed, and relevant curves were created using SPSS 23.0. Unless otherwise stated, mean values and standard deviations are reported. Student's t test was used for comparisons between subgroups. For categorical variables, the chi-square test or Fisher's exact test was used, as appropriate. The kappa test was used to evaluate the consistency between clinical stage and pathologic stage. Survival curves were constructed using the Kaplan\u0026ndash;Meier method, which was also used for univariate analysis. Variables with a P value less than 0.1 were included in the Cox proportional hazards model.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e \u003cb\u003e1. Clinical pathological data\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe characteristics of the 1639 patients enrolled in this study are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age of the patients was 56 years. Postoperative pathology revealed that more than half of the patients (75.3%) had proven T3-T4. The tumour location was the upper oesophagus in 265 patients (16.2%), the middle oesophagus in 1240 patients (75.7%), and the lower oesophagus in 134 patients (8.2%). There were 668 patients without LN metastases (40.8%) and 971 patients with LN metastases (59.2%). Of the 971 patients with LN involvement, 805 patients (49.1%) had at least 1 positive LN but were SCLN-negative, and 166 patients (10.1%) had SCLN metastasis. According to the tumour location, the frequency of SCLN metastasis was 14.0% in patients with upper oesophageal tumours, 9.5% in patients with middle oesophageal tumours, and 8.2% in patients with lower oesophageal tumours. The median number of resected nodes was 24.44 (range 1\u0026thinsp;~\u0026thinsp;74) in this study.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatients\u0026rsquo; characteristics and tumor data\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic and finding\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo. (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age (range), y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56(30\u0026ndash;82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1231(75.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e408(24.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e265(16.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1240(75.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134(8.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDegree of pathological differentiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWell-differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e280(17.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerately-differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1085(66.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoorly-differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e274(16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathologic T classification\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e137(8.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e268(16.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e968(59.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e266(16.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathologic positive node no. (including supraclavicular node)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e668(40.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e471(28.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(3\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e346(21.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(7-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e154(9.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathologic M classification\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM1 (supraclavicular node)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e166(10.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003e2. Survival analysis\u003c/b\u003e \u003c/p\u003e\u003cp\u003eThe median overall survival (OS) across all patients was 50.20 months, and the 5-year survival rate was 55.4%. The 5-year survival rate was 74.1% for patients with N0, 44.3% for node-positive patients without SCLN disease, and 33.7% for node-positive patients with SCLN metastasis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e); these differences between pN (+) SCLN(-) and pN (+) SCLN(+) were significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Among those patients without SCLN metastasis, the 5-year survival rate was 46.7% for patients with 1\u0026ndash;2 positive LNs (pN1), 43.9% for patients with 3\u0026ndash;6 positive LNs (pN2), and 18.6% for patients with more than 7 positive LNs (pN3). The 5-year survival rate in the SCLN-positive group was more similar to that in the N2 group (P\u0026thinsp;=\u0026thinsp;0.342) than that in the N3 group (P\u0026thinsp;=\u0026thinsp;0.027) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAccording to the univariate analysis of survival (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), the male sex (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), poorer degree of pathological differentiation (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), a higher T stage (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), a higher N stage (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and metastasis to SCLNs (P\u0026thinsp;=\u0026thinsp;0.020) were associated with worse 5-year OS.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate analysis of factors for survival\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-y Survival (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.555\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e54.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e55.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.950\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e55.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.906\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDegree of pathological differentiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWell-differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e64.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerately-differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e54.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.449\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoorly-differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e49.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.649\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathologic T classification\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e81.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.397\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e55.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.852\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.221\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathologic N classification (including supraclavicular node)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e74.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.237\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(3\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(7-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.366\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSupraclavicular lymph node (positive lymph node\u0026thinsp;\u0026gt;\u0026thinsp;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.281\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(3\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(7-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\u003cp\u003e \u003cb\u003e3. Stratified analysis based on location\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAmong patients with upper thoracic oesophageal tumours, the 5-year survival rate was 69.1% for lymph node negative patients, 42.4% for lymph node positive patients without SCLN metastasis, and 51.4% for patients with SCLN metastasis (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). The difference between the pN(+)SCLN(-) group and the pN(+)SCLN(+) group was not significant (p\u0026thinsp;=\u0026thinsp;0.562). Among patients with middle thoracic oesophageal tumours, the 5-year survival rate was 74.6% for lymph node negative patients, 44.6% for lymph node positive patients without SCLN metastasis, and 28.8% for patients with SCLN metastasis (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). The difference between the pN(+)SCLN(-) group and the pN(+)SCLN(+) group was significant (p\u0026thinsp;=\u0026thinsp;0.004). Among patients with lower thoracic oesophageal tumours, the 5-year survival rate was 81.0% for lymph node negative patients, 45.7% for lymph node positive patients without SCLN metastasis, and 27.3% for patients with SCLN metastasis (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). The difference between the pN(+)SCLN(-) group and the pN(+)SCLN(+) group was not significant (p\u0026thinsp;=\u0026thinsp;0.807). According to the analysis of the number of involved LNs, including the SCLNs, patients with more positive nodes showed significantly worse survival (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003e4. Multivariate analysis\u003c/b\u003e \u003c/p\u003e\u003cp\u003eA multivariate analysis was performed using factors that were significant in the univariate analysis. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows that the male sex (P\u0026thinsp;=\u0026thinsp;0.001), poorer degree of pathological differentiation (P\u0026thinsp;=\u0026thinsp;0.045), a higher T stage (P\u0026thinsp;=\u0026thinsp;0.005), and more positive nodes (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) retained statistical significance as adverse prognostic factors for OS, while SCLN metastasis did not (P\u0026thinsp;=\u0026thinsp;0.956). As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e5\u003c/span\u003eA, \u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e5\u003c/span\u003eB, and \u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e5\u003c/span\u003eC, in patients with the same number of positive nodes, the SCLN status did not predict survival outcomes. Although the 5-year OS was worse in patients with SCLN metastases, this may be related to other confounding factors including T-stage and N-stage rather than SCLN status.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate analysis of factors for survival\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRisk ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale/Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.136\u0026ndash;1.648\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDegree of pathological differentiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerately,Poorly-differentiated/Well-differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.246\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.005\u0026ndash;1.546\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3,T4/T0,T1,T2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.091\u0026ndash;1.605\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of positive nodes including supraclavicular nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(1\u0026ndash;2)/N0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.737\u0026ndash;2.595\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(3\u0026ndash;6)/N0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.956\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.391\u0026ndash;3.655\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN(7-)/N0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.745\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.654\u0026ndash;6.161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSupraclavicular node\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive/negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.804\u0026ndash;1.259\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.956\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe accurate staging of oesophageal cancer is essential for predicting patient prognosis, as different stages provide critical guidance for assessing outcomes and informing treatment decisions. The current staging systems for oesophageal cancer primarily include the primary tumor (T stage), lymph node metastasis (N stage), and distant metastasis (M stage), with the N stage being a key component of the system. Adequate lymph node dissection facilitates a more precise N stage evaluation. While 3-field lymphadenectomy provides comprehensive nodal staging and potential survival benefits in thoracic ESCC, its associated complications warrant careful consideration. Mine et al.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] noted increased operative time and mortality with prophylactic SCLN dissection. Patient selection and targeted dissection are critical to balance efficacy and safety. However, differences persist between Eastern and Western approaches to lymph node dissection in oesophageal cancer, particularly regarding the necessity of supraclavicular lymph node (SCLN) dissection.\u003c/p\u003e \u003cp\u003eThe AJCC consistently classifies SCLN as distant metastasis. In the 7th edition of the international oesophageal cancer staging system published in 2009, the M1 subgroup (M1a and M1b) was eliminated, and SCLN metastasis was defined as distant metastasis. Rice et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] analyzed 480 postoperative oesophageal cancer patients and found a significant survival difference between patients with M0 and M1 stages. However, no survival differences were observed between the M1a and M1b stages, prompting recommendations to eliminate the M1 subgroup. Similarly, Wijnhoven et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] reported comparable 5-year survival rates between M1a and M1b patients, supporting this perspective. The AJCC's classification of SCLN as an M stage is based on its biological characteristics as distant metastasis and its influence on prognosis. The evidence for the AJCC 8th edition staging system was derived from the WEC database, which focuses solely on the number of positive lymph nodes without considering their anatomical location [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Conversely, the JES staging system for abdominal lymph nodes adopts the Japanese gastric cancer staging, with specific modifications for mediastinal and cervical lymph nodes tailored to oesophageal cancer, supported by extensive research on lymph node metastasis locations in Japan [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Chang et al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] used propensity score matching analysis to compare the prognostic accuracy of the JES 11th edition and AJCC 8th edition systems in patients with thoracic oesophageal squamous cell carcinoma (ESCC). Their findings showed the AJCC 8th edition outperformed the JES 11th edition in predicting prognosis. Zhang et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] compared the two systems in Chinese ESCC patients, concluding that both had similar prognostic performance. In earlier JES editions, SCLN was classified as a regional lymph node: a second station for upper and middle thoracic oesophageal cancer and a third station for lower thoracic oesophageal cancer. However, there remains controversy over the benefits of SCLN dissection. In the 12th edition of the JES staging system, SCLN was redefined as an extraregional lymph node (M1a stage)[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e][\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Some clinical studies indicate that the prognosis of SCLN metastasis is better than that of visceral metastasis. For example, Shim et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] reported higher survival rates in patients with SCLN metastasis than in those with visceral organ metastasis, while Chao et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] observed significantly improved survival rates in patients with SCLN metastasis after chemoradiotherapy compared to those with visceral metastasis. In summary, the classification of SCLN in thoracic oesophageal cancer remains contentious between Eastern and Western perspectives. Further large-scale studies are needed to clarify whether SCLN should be considered a regional lymph node.\u003c/p\u003e \u003cp\u003eIn this study, we analyzed 1,639 patients with ESCC who underwent 3-field lymphadenectomy. While patients with SCLN metastasis had significantly worse prognoses than those without SCLN metastasis, SCLN metastasis was not identified as an independent prognostic factor. Therefore, SCLN should be included as part of regional lymph node dissection in ESCC. The metastasis rate to SCLN in this study was 10.1%, consistent with previous reports of approximately 10% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e][\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The mean number of dissected lymph nodes ranged from 1 to 74, with an average of 24.44 nodes. Among patients with SCLN metastasis, the mean number of dissected lymph nodes was 27.31. The SCLN metastasis rate varied depending on the tumor's location: Tachimori et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e][\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] reported rates of 6.3\u0026ndash;21.2% for upper thoracic tumors, 6.9\u0026ndash;25.5% for middle thoracic tumors, and 3.7\u0026ndash;6.2% for lower thoracic tumors. Similarly, our study found rates of 14.0%, 9.5%, and 8.2% for upper, middle, and lower thoracic tumors, respectively. These findings confirm the risk of SCLN metastasis regardless of the tumor's primary location. Survival analysis revealed that the pN (+) SCLN(-) group had better outcomes than the pN (+) SCLN(+) group. Univariate analysis confirmed that SCLN metastasis is closely associated with ESCC prognosis. However, stratified analysis by N stage showed no significant difference in 5-year survival rates between patients with and without SCLN metastasis within the same N stage. This suggests that SCLN behaves more like a regional lymph node, consistent with studies by domestic and Japanese researchers [[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e][\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e][\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSome studies argue that for middle and upper thoracic ESCC, SCLN should be considered a regional lymph node rather than distant metastasis [[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e][\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e][\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Subgroup analyses by tumor location in this study showed that among upper and lower thoracic patients, the survival rates of the pN (+) SCLN(-) group and pN (+) SCLN(+) group were comparable. However, for middle thoracic patients, the pN (+) SCLN(-) group had significantly better survival rates than the pN (+) SCLN(+) group. Further studies with larger sample sizes are required to confirm the impact of SCLN metastasis on prognosis in lower thoracic cases. Further multivariate analyses were performed and found that only the number of LNs, gender (male) and higher T-stage were found to be independent risk factors for survival outcomes, while SCLN metastasis was not an independent risk factor for prognosis in patients with oesophageal squamous carcinoma. Therefore, SCLN should be classified as part of the regional lymph nodes of oesophageal squamous carcinoma.\u003c/p\u003e \u003cp\u003eIn this study, we found that the prognosis of the SCLN metastasis group was similar to that of the pN2 stage and significantly superior to that of the pN3 stage. The similarity in survival between SCLN-positive (33.7%) and N2 patients (43.9%, P\u0026thinsp;=\u0026thinsp;0.342) is driven by nodal burden, not anatomical location. Multivariate analysis confirmed that survival disparities are explained by N-stage (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), not SCLN status (P\u0026thinsp;=\u0026thinsp;0.956). This aligns with studies showing nodal quantity, not station, dictates prognosis in ESCC [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Therefore, we suggest that SCLN metastasis could be considered as part of N2 staging in subsequent staging updates to improve the accuracy of staging.\u003c/p\u003e \u003cp\u003eWhile our study primarily focused on the prognostic role of SCLN metastasis in the era of surgical resection, recent advancements in systemic therapies, particularly immunotherapy, have reshaped the landscape of esophageal cancer management. Immune checkpoint inhibitors have demonstrated efficacy in both locally advanced and metastatic ESCC, with potential implications for lymph node metastasis control. For instance, the KEYNOTE-181 trial reported that pembrolizumab significantly improved overall survival in patients with advanced ESCC, including those with lymph node involvement.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] Similarly, the CheckMate 577 trial highlighted the role of adjuvant nivolumab in reducing recurrence risk post-surgery, which may indirectly influence the management of regional nodes such as SCLNs.[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] Emerging evidence also suggests that immunotherapy could enhance the therapeutic effect of lymphadenectomy by targeting micrometastases. A recent multicenter study by Li et al. observed that neoadjuvant PD-1 blockade combined with chemotherapy resulted in higher pathological complete response rates in lymph nodes compared to chemotherapy alone.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] These findings raise the possibility that future staging systems may need to account for the synergistic effects of immunotherapy and surgery, potentially redefining the prognostic significance of SCLN metastasis. However, our study's cohort predates the widespread use of immunotherapy, and further prospective studies are warranted to validate its impact on SCLN classification.\u003c/p\u003e \u003cp\u003eAs a large retrospective study containing data on 3-field lymphadenectomy in 1,639 cases of oesophageal squamous carcinoma, this study provides an important evidence-based basis for the clinical management of oesophageal cancer. Of course, this study has some limitations. First, the retrospective study design is an important limitation of this study. Retrospective studies usually rely on existing medical records, which may limit the completeness and accuracy of the data. In addition, retrospective studies are subject to selection bias. Second, the study was included over a relatively long period of time, and changes have occurred in the treatment methods and perioperative management of oesophageal cancer in the last few years, which can have an impact on the prognosis of patients. Finally, being a single-centre study, there is still a need to include more centres in the future to expand the sample size to validate the findings of this study. We will continue our efforts to improve the quality and applicability of the study and look forward to future studies that will provide more accurate and comprehensive results.\u003c/p\u003e \u003cp\u003eThe study suggests that SCLN should be considered part of regional lymph nodes in ESCC and proposes incorporating SCLN metastasis into the N2 stage for improved staging accuracy and patient outcomes, \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ethough further validation through prospective multi-center studies is warranted.\u003c/span\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding Information\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003eThe authors did not receive support from any organization for the submitted work. No funding was received to assist with the preparation of this manuscript. No funding was received for conducting this study. No funds, grants, or other support was received. The authors have no relevant financial or non-financial interests to disclose.All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003eThe authors have no conflict of interest.The authors have no competing interests to declare that are relevant to the content of this article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003eApproval of the research protocol by an Institutional Reviewer Board: K2024-063-01\u003c/p\u003e\n\u003cp\u003eInformed Consent: N/A\u003c/p\u003e\n\u003cp\u003eRegistry and the Registration No. of the study/trial: N/A\u003c/p\u003e\n\u003cp\u003eAnimal Studies: N/A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePengqiang Gao and Junpeng Lin contributed equally to this work.\u003c/p\u003e\n\u003cp\u003eFeng Wang conceived and designed the study.\u003c/p\u003e\n\u003cp\u003ePengqiang Gao, Junpeng Lin, Xiaofeng Chen, Peiyuan Wang, Hui Lin, Hang Zhou, Shuoyan Liu, and Feng Wang contributed to data collection, analysis, and interpretation.\u003c/p\u003e\n\u003cp\u003ePengqiang Gao and Junpeng Lin drafted the manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors reviewed, edited, and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments. The study protocol was approved by the Ethics Committee of Fujian Cancer Hospital (Approval No. K2024-444-01). As this was a retrospective analysis of de-identified existing data, the committee granted a waiver of informed consent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003eThis retrospective study was approved by the Institutional Review Board of Fujian Cancer Hospital (Approval No. K2024-444-01). Due to the retrospective nature of the study and the use of anonymized data, the requirement for informed consent was waived by the ethics committee.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e:The authors declare no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e:The datasets generated and/or analysed during the current study are not publicly available due to patient privacy and confidentiality reasons but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003e\u003cu\u003eSung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. 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J Thorac Cardiovasc Surg. 2014;148 (4):1224-1229. doi:10.1016/j.jtcvs.2014.02.008.\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003e\u003cu\u003eUdagawa H, Ueno M, Shinohara H, et al. The importance of grouping of lymph node stations and rationale of three-field lymphoadenectomy for thoracic esophageal cancer. J Surg Oncol. 2012;106 (6):742-747. doi:10.1002/jso.23122.\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003e\u003cu\u003eKojima T, Shah MA, Muro K, et al. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020;38 (35):4138-4148. doi:10.1200/JCO.20.01888\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003e\u003cu\u003eKelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021;384 (13):1191-1203. doi:10.1056/NEJMoa2032125\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003e\u003cu\u003eLiu J, Yang Y, Liu Z, et al. Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma. J Immunother Cancer. 2022;10 (3): e004291. doi:10.1136/jitc-2021-004291\u003c/u\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Oesophageal carcinoma, Oesophagectomy, Supraclavicular lymph nodes, Survival rate; Prognosis","lastPublishedDoi":"10.21203/rs.3.rs-9406877/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9406877/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe definitions of regional nodes differ between the 12th edition of the JES and the UICC staging systems, and the most prominent difference is in the status of the supraclavicular lymph nodes (SCLN). This study was designed to investigate the prognostic impact of metastasis to SCLN in patients with thoracic oesophageal squamous cell carcinoma (ESCC). The study group consisted of 1639 patients with thoracic ESCC who underwent oesophagectomy with 3-field lymphadenectomy at the Department of Thoracic Surgery, Fujian Cancer Hospital and whose clinical and survival information were collected.Of the 1639 patients, 668 (40.8%) had no lymph node metastases, 805 (49.1%) had at least 1 positive node but were SCLN-negative, and 166 (10.1%) had SCLN metastases. The 5-year survival rate was 74.1% for node-negative patients, 44.3% for node-positive patients without SCLN metastases, and 33.7% for patients with SCLN metastases. A comparison of the 5-year survival rates among patients with SCLN metastases revealed that the SCLN-positive group was more similar to the N2 group (P\u0026thinsp;=\u0026thinsp;0.342) than to the N3 group (P\u0026thinsp;=\u0026thinsp;0.027). In the multivariate analysis, the male sex (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), a higher pT stage (P\u0026thinsp;=\u0026thinsp;0.005), a poorer degree of pathological differentiation (P\u0026thinsp;=\u0026thinsp;0.045), and a higher N stage (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) retained statistical significance as adverse prognostic factors for overall survival, while SCLN metastasis did not (P\u0026thinsp;=\u0026thinsp;0.956). The survival benefit of 3-field lymphadenectomy including metastases to SCLNs was indicated in patients with thoracic ESCC. SCLNs appear to be regional nodes similar to other regional nodes.\u003c/p\u003e","manuscriptTitle":"Prognostic Impact of Supraclavicular Lymph Node Metastasis in Thoracic Oesophageal Squamous Cell Carcinoma in a Large Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-18 08:17:37","doi":"10.21203/rs.3.rs-9406877/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-21T09:25:36+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-13T06:41:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"30108471414183300847437394972443404422","date":"2026-05-08T06:11:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T05:57:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"240857138091420004733406383446262662893","date":"2026-05-08T02:20:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"101320839874762521771458136331368644568","date":"2026-05-07T22:59:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-07T16:26:23+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-05-05T06:22:15+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-30T13:02:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-28T15:40:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2026-04-28T13:36:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9dae9056-d178-45fc-9188-5640fb88f798","owner":[],"postedDate":"May 18th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-21T09:25:36+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-13T06:41:59+00:00","index":49,"fulltext":""},{"type":"reviewerAgreed","content":"30108471414183300847437394972443404422","date":"2026-05-08T06:11:07+00:00","index":46,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T05:57:42+00:00","index":45,"fulltext":""},{"type":"reviewerAgreed","content":"240857138091420004733406383446262662893","date":"2026-05-08T02:20:03+00:00","index":44,"fulltext":""},{"type":"reviewerAgreed","content":"101320839874762521771458136331368644568","date":"2026-05-07T22:59:47+00:00","index":43,"fulltext":""},{"type":"reviewersInvited","content":"8","date":"2026-05-07T16:26:23+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-05-05T06:22:15+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-21T09:40:43+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-18 08:17:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9406877","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9406877","identity":"rs-9406877","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}