Improved Survival of Primary-Tumor Resection in Metastatic Thoracic Esophageal Cancer: A Population-Based, Propensity Score Matched Study

Improved Survival of Primary-Tumor Resection in Metastatic Thoracic Esophageal Cancer: A Population-Based, Propensity Score Matched 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 Article Improved Survival of Primary-Tumor Resection in Metastatic Thoracic Esophageal Cancer: A Population-Based, Propensity Score Matched Study Jiayan Wu, Haosheng Zheng, Gengfeng Wang, Fei Qin, Yuzhen Zheng, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4930346/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract The study aims to assess the survival effect of primary-tumor resection (PTR) on thoracic esophageal cancer with distant metastasis(TECDM). Data of patients with TECDM was collected from the Surveillance, Epidemiology, and End Results database from 2010 to 2020. We used a 1:1 propensity-score matching(PSM) analysis to minimize heterogeneity between different groups. Total 7733 patients with TECDM were included, and 121 patients and 7612 patients underwent primary-tumor resection and did not, respectively. Patients underwent primary-tumor resection had a better median OS and median CSS than those patients did not in overall and PSM cohort. In PSM cohort, the median OS was 11 months (95% CI, 9 months to 13 months) for TECDM patients with PTR and 7 months (95% CI, 5 months to 9 months) for those patients without PTR. Additionally, cox proportional hazard models similarly indicated that PTR was a significantly protective factor for TECDM patients in OS (HR: 0.5529; 95% CI, 0.5196 to 0.7730, P < 0.001) and CSS (HR:0.5869 ; 95% CI, 0.479 to 0.7192, P < 0.001). In conclusion, primary-tumor resection prolongs survival of thoracic esophageal cancer patients with distant metastasis. Biological sciences/Cancer/Lung cancer Health sciences/Oncology/Surgical oncology esophageal cancer distant metastasis primary-tumor resection prognosis SEER Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Esophageal cancer(EC), the ninth most common malignancy, is the sixth leading cause, globally, of malignant tumor deaths ( 1 , 2 ). Due to lack of consistent and effective early screening algorithms, most esophageal cancer patients were diagnosed at local advanced stage and some of them were even diagnosed with distant metastases ( 3 ). For patients with distant metastases, treatment were usually limited to systemic chemotherapy or best supportive care according to patients’ performance status. And local therapies such as radiation or palliative resection of primary tumor could be considered to improve quality of life or reduce the esophageal cancer relative symptoms such as obstruction or bleeding for metastatic esophageal cancer patients ( 4 – 6 ). However, it was reported that metastatic esophageal cancer patients who underwent palliative esophagectomy had a better survival than those without esophagectomy ( 7 ). But after esophagectomy, distant metastatic recurrence frequently occurs ( 8 ). Consequently, whether primary-tumor resection improves the prognosis of metastatic esophageal cancer patient remains controversial. The aim of this present study is to assess the survival effect of primary-tumor resection in TECDM patients. Results Baseline characteristics In the present study, total 9680 thoracic esophageal cancer patients with distant metastasis, diagnosed with histologically confirmation, between 2010 and 2020 were collected from the SEER database. Under the inclusion criteria and exclusion criteria, 7733 patients were included in our study (Fig. 1 ). Of those patients, 121 patients underwent primary-tumor resection whereas 7612 patients did not. The baseline clinical and pathological characteristics of the included patients are showed in Supplementary Table 1. To balance the possible covariates such as diagnosis year, age, gender, race, marital status at diagnosis, median household income, differentiation of tumor, T stage of tumor, N stage of tumor, histologically type, location of tumor, size of tumor, chemotherapy, radiotherapy between primary-tumor resection group and no-surgery group, a 1:1 Propensity Score Matched(PSM) analysis was performed. After PSM, the clinical and pathological characteristics is well-balanced in the matched cohort (Supplementary Table 1). Survival outcomes of primary-tumor resection before PSM Kaplan-Meier analysis were performed to evaluate overall survival (OS) and cancer-specific survival (CSS) of TECDM patients with primary-tumor resection(PTR) before PSM, and the log-rank test was used to compare any survival differences between the two groups. The results showed that TECDM patients with PTR had a significantly better median OS( p < 0.001, Fig. 2 A) and CSS(p < 0.001, Fig. 2 B) than TECDM patients without PTR. The median OS of TECDM patients with PTR were 11.0 months (95% CI, 9 months to13 months) and of TECDM patients without PTR were 4 months (95% CI, 4 months to 5 months). And the median CSS of those TECDM patients underwent PTR and of those TECDM patients without PTR was 9.0 months (95% CI, 7 months to 11 months) and 4 months (95% CI, 4 months to 4 months), respectively. In addition, Cox proportional hazards regression model was used to identify independent prognostic factors for CSS and OS in overall cohort. Multivariate Cox model analysis in the overall cohort showed that PTR, diagnosis year, age, race, marital status at diagnosis, median household income, differentiation of tumor, T stage of tumor, N stage of tumor, histologically type, location of tumor, size of tumor, chemotherapy, radiotherapy were independent prognostic factors for CSS in TECDM patients(Supplementary Table 2). Multivariate Cox model analysis revealed that PTR, age, marital status at diagnosis, median household income, differentiation of tumor, T stage, histologically type, tumor size, chemotherapy, radiotherapy were independent prognostic factors for OS in TECDM patients(Supplementary Table 2). Interestingly, PTR was a protective factor of OS in TECDM patients (HR:0.5529; 95% CI, 0.4537 to 0.6738, P < 0.001). Survival outcomes of primary-tumor resection after PSM In the PSM cohort, TECDM patients with PTR also had a significantly better median OS (p < 0.001, Fig. 2 C) and CSS(p < 0.001, Fig. 2 D) than TECDM patients without PTR. After PMS, the median OS of those TECDM patients underwent PTR and of those TECDM patients without PTR was 11.0 months (95% CI, 9 months to 13 months) and 7 months (95% CI, 5 months to 9 months), respectively. And the median CSS of those TECDM patients underwent PTR and of those TECDM patients without PTR was 9.0 months (95% CI, 7 months to 11 months) and 6 months (95% CI, 4 months to 9 months), respectively. Furthermore, Cox proportional hazards model was performed to confirm the prognostic significance of PTR in patients with thoracic esophageal cancer with distant metastasis. Furthermore, multivariate Cox analysis in the matched cohort showed that PTR was independent protective factors for OS (Fig. 3 ) and CSS in TECDM. Subgroup analysis of survival outcomes of primary-tumor resection Multivariate Cox model analysis revealed that PTR, age, median household income, differentiation of tumor, T stage of tumor, histologically type, size of tumor, chemotherapy, radiotherapy were independent prognostic factors for OS in TECDM patients. Next, subgroup analysis was performed to further explore the impact of PTR on OS in TECDM patients. In the age subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in year 65 subgroups(P 60 000 and income < 60 000 subgroups( P < 0.001, Fig. 4 B); In differentiation of tumor subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in GradeⅠ-Ⅱ and GradeⅢ-Ⅳ subgroups( P < 0.001, Fig. 4 C); In T stage of tumor subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in T1-T2 and T3-T4 subgroups( P < 0.001, Fig. 4 D); In histologically type subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in Squamous and Adenocarcinoma subgroups( P 5mm and < 5mm subgroups( P < 0.001, Fig. 4 F). Similarly, subgroup analysis was performed to further explore the impact of other treatments on OS and CSS in TECDM patients. In chemotherapy subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in chemotherapy and no-chemotherapy subgroups( P < 0.001, Fig. 5 A; P < 0.001, Fig. 5 B); Besides, in radiotherapy subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in radiotherapy and no-radiotherapy subgroups( P < 0.001, Fig. 5 C; P < 0.001, Fig. 5 D). Discussion Thoracic esophageal cancer with distant metastasis(TECDM), as one of the severe fatal disease, is considered as an advanced esophageal cancer with poor long-term prognosis ( 9 ). Neoadjuvant chemotherapy with or without radiotherapy followed by esophageal surgery is the cornerstone of locally advanced esophageal cancer treatment ( 10 , 11 ). But thoracic esophageal cancer with distant metastasis was unsuitable for primary tumor resection and recommended treatment for TECDM is systematic therapies ( 9 ). According to NCCN Clinical Practice Guideline, systemic therapy regimens were recommended for metastatic thoracic esophageal cancer. And with aim of relieving symptom and improving in quality of life, palliative supportive care in metastatic thoracic esophageal cancers is encouraged ( 12 ). Similarly, the European Society for Medical Oncology (ESMO) Clinical Practice Guideline does not consider surgery as a treatment option for thoracic esophageal cancer patients with distant metastasis. And the recommended treatment is palliative chemotherapy ( 13 ). Besides, the ESMO Clinical Practice Guidelines state that patients with metastatic esophageal cancer may be considered for different palliative care options such as external radiotherapy, gastrostomy, jejunostomy and metal stent insertion based on their clinical situation ( 14 ). However, considering the benefits of primary-tumor surgery for patients with colorectal cancer and liver metastases, an increasing number of surgeons are focusing on the role of primary tumor surgery in metastatic cancer patients ( 15 , 16 ). For metastatic esophageal cancer, a retrospective study have shown that primary-tumor surgery significantly improve survival in patients with TECDM ( 17 ). But limited by small samples and single center data, the survival benefit of primary- tumor surgery to thoracic esophageal cancer patients with distant metastases need to be further confirmed. In a word, primary-tumor resection in metastatic esophageal cancer remains controversial and debated. In our present study, total 121 patients from multiple centers in USA underwent esophageal primary tumor resection. As a result, primary-tumor resection, an independent prognostic factor, improves overall survival and cancer-specific survival of the thoracic esophageal cancer patients with distant metastasis. First of all, using the SEER data of demographics and survival information, the study showed that great improvements of OS and CSS for TECDM patients with primary-tumor resection in overall cohort. What is more, after Propensity Score Matching, aiming to balance the possible covariates between PTR group and no-PTR group, PTR improves overall survival and cancer-specific survival of the thoracic esophageal cancer patients with distant metastasis in PSM cohort. And multivariate Cox model analysis revealed that PTR, age, median household income, differentiation of tumor, T stage of tumor, histologically type, size of tumor, chemotherapy, radiotherapy were independent prognostic factors for OS in TECDM patients. Last but not the least, in all subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR. The results align with previous retrospective studies in other metastatic gastric, ovarian, kidney and neuroendocrine tumors, primary- tumor resection can lead to the better survival ( 18 – 22 ). We used propensity score matched (PSM) analysis to reduce the possible influence of some potential covariates, between primary-tumor resection group and no-surgery group, that might distort the real relation of primary-tumor resection with CSS and OS. In other words, our study minimized the selection bias of patients to receive PTR. Besides, the present studies focused specifically on metastatic thoracic esophageal cancer patients that are more suitable for surgical resection than other sites. Why primary-tumor surgery is able to prolong the survival of tumor patients with metastasis remains unclear. It was reported that one possible mechanism that primary-tumor resection decreased circulating tumor cells of the blood contributing to distant metastases ( 23 , 24 ). Besides, primary-tumor resection might recover the immune system to prolong the survival of patients with metastatic tumor ( 25 – 27 ). Hence, in the present study, primary-tumor resection might improve overall survival and cancer-specific survival of the thoracic esophageal cancer patients with distant metastasis by decreasing circulating tumor cells of the blood and restoring the function of immune system. However, some opponents consider that primary-tumor resection might accelerate metastasis, which is related to the angiogenesis and growth of metastases after primary tumor resection ( 28 ). Additionally, primary-tumor resection for patients with metastatic esophageal cancer does not significantly improve five-year survival, but increase preoperative or postoperative complications and thus delay systemic therapy ( 29 ). Besides, primary-tumor resection increases medical costs and might lead to low quality of life after surgery ( 30 ). Consequently, the multidisciplinary team should assess whether thoracic esophageal cancer patients with distant metastasis are suitable for resection of primary tumor. There are also some limitations in the present study. First of all, the present study, as a retrospective research, has its natural limitation of selection bias. Consequently, propensity score matched (PSM) was used to reduce the possible confounding bias between the PTR group and no-PTR group, making our conclusions more reliable. What is more, due to limitation of incomplete information from SEER database, some information such as performance status is unreported. Therefore, well-designed randomized control trials should be performed to verify our findings. Conclusions In conclusion, the retrospective study showed that primary-tumor resection is associated with good overall survival and cancer-specific survival in thoracic esophageal cancer patients with distant metastasis. Material and Methods Data source and patients selection The SEER*Stat software (version 8.4.3) was used to download detailed information including patient demographics and survival information. All thoracic esophageal cancer patients with distant metastasis(TECDM) at diagnosis between the years 2010 and 2020 were identified(Fig. 1 ). Firstly, thoracic esophageal cancer patients with distant metastasis were retrieved using the Primary Site - labeled value{Site - labeled = 'C15.1-Thoracic esophagus', 'C15.3-Upper third of esophagus', 'C15.4-Middle third of esophagus', 'C15.5-Lower third of esophagus', 'C15.8-Overlapping lesion of esophagus'}. Secondly, TECDM with microscopically diagnosed at diagnosis between the years 2010 and 2020 were selected. The inclusion criteria were as follows: ( 1 ) diagnosed with esophageal cancer only; ( 2 )confirmed distant metastases; ( 3 ) diagnosed with histologically confirmation; ( 4 ) treatment information of primary tumor was known. The exclusion criteria were as follows: ( 1 ) patients diagnosed with over one primary tumor; ( 2 ) treatment information of primary tumor was unknown. Thirdly, demographics and survival information was collected as followed: ( 1 )diagnosis year; ( 2 )age; ( 3 )gender; ( 4 )race record; ( 5 )marital status at diagnosis; ( 6 ) median household income; ( 7 ) residence record; ( 8 )PRCDA record; ( 9 ) reporting source; ( 10 ) differentiation of tumor; ( 11 ) T stage; ( 12 )N stage; ( 13 ) histologically type; ( 14 )tumor location; ( 15 )tumor size ( 16 )Chemotherapy; ( 17 ) Radiotherapy; ( 19 ) resection of primary tumor; ( 19 ) survival months; ( 20 )Vital status record. Propensity Score Matched (PSM) Propensity score matched (PSM) was used to reduce the possible influence of potential covariates between primary-tumor resection group and no-surgery group. With the nearest neighbor matched method of setting caliper value 0.1, included patients were matched 1:1 into primary-tumor resection and no-surgery group. In the present study, the covariates used for PSM were as follows: diagnosis yea, age record, gender, race record, marital status at diagnosis, median household income, differentiation of tumor, T stage of tumor, N stage of tumor, histologically type, location of tumor, size of tumor, Chemotherapy, Radiotherapy. Statistical Analysis The chi-square test was performed to compare categorical variables in the present study with the aims of revealing any differences of clinical and pathological characteristics between the primary-tumor resection group and no-surgery group. Kaplan-Meier analysis was performed to evaluate overall survival (OS) and cancer-specific survival (CSS) of TECDM patients with primary tumor resection(PTR) before and after PSM, and the log-rank test was used to compare any survival differences between the primary-tumor resection group and no-surgery group. Cox proportional hazards regression model was used to identify independent prognostic factors for CSS and OS in our study. Variables with P < 0.05 in the univariate Cox model were further put into the multivariate Cox model analysis. All statistical analyses in the present study were performed using R software(version 4.3.1 ), and a two sided P value less than 0.05 was considered statistical significance. Ethics Statement Approval of the study was given by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University(2023ZSLYEC-342). This study strictly complied with the Declaration of Helsinki, and all data in the present study was obtained from the SEER database with no need for informed patient consent. Declarations Conflicts of Interest: All authors declare no conflict of interest. Data Sharing Statement The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request. Funding statement: This work was supported by National Key Clinical Discipline & the National Natural Science Foundation of China [grant number 82102955] & No.2: the Guangzhou Basic Research Project [grant number 202201011326]. Author Contribution JY W, XY Q , GF W and HS z wrote the main manuscript text; F Q, Z L, BZ J, YZ Z, JG C and HY L prepared figures 1-5. All authors reviewed the manuscript. Data Availability The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request. References Sung, H. et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71 , 209–249. 10.3322/caac.21660 (2021). Bray, F. et al. Global cancer statistics 2022: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 74 , 229–263. 10.3322/caac.21834 (2024). Demarest, C. T. & Chang, A. C. 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Supplementary Files STable1.Baselinecharacteristicsoftheselectedpatientsbeforeandafterpropensityscorematching..docx STable2.UnivariateandmultivariateanalysisofprognosticfactorsforOSintheoverallcohort.docx Cite Share Download PDF Status: Published Journal Publication published 24 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 25 Nov, 2024 Reviews received at journal 24 Nov, 2024 Reviewers agreed at journal 12 Nov, 2024 Reviews received at journal 19 Oct, 2024 Reviewers agreed at journal 09 Oct, 2024 Reviewers invited by journal 04 Sep, 2024 Editor assigned by journal 04 Sep, 2024 Editor invited by journal 29 Aug, 2024 Submission checks completed at journal 27 Aug, 2024 First submitted to journal 17 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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14:57:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4930346/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4930346/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-85419-y","type":"published","date":"2025-01-24T15:57:43+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66859831,"identity":"27c58bb0-2fda-48d6-bed6-de1fe75aad9d","added_by":"auto","created_at":"2024-10-17 08:15:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":181471,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patients selection in the study.\u003c/p\u003e","description":"","filename":"Onlinefigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4930346/v1/0395c7a4a21304713263ed89.png"},{"id":66858322,"identity":"9c5e9433-6e4c-4302-94bb-03c7908cf481","added_by":"auto","created_at":"2024-10-17 08:07:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":350850,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves for overall survival and cancer-specific survival of TECDM patients with primary-tumor resection versus without primary-tumor resection before and after PSM.\u003c/p\u003e","description":"","filename":"Onlinefigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4930346/v1/906801994197ea29133f7148.png"},{"id":66859832,"identity":"f37e9712-3b4d-46c3-ac8a-4062a86c3724","added_by":"auto","created_at":"2024-10-17 08:15:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":668283,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot showing results of multivariate Cox regression model analysis to explore the independent prognostic factors for overall survival in the PSM cohort.\u003c/p\u003e","description":"","filename":"Onlinefigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4930346/v1/9f65948537935d7eed9798c4.png"},{"id":66858325,"identity":"13d76b05-e30b-4c3a-a48c-49d0cc549e29","added_by":"auto","created_at":"2024-10-17 08:07:23","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":581447,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves for overall survival and cancer-specific survival of TECDM patients with primary-tumor resection versus without primary-tumor resection stratified by clinicopathologic characteristics in the overall cohort.\u003c/p\u003e","description":"","filename":"Onlinefigure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4930346/v1/c2c7922d5062d315015a7071.png"},{"id":66858324,"identity":"9eec8795-cbaf-4b2b-8749-71650e26bb27","added_by":"auto","created_at":"2024-10-17 08:07:23","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":412081,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves for overall survival and cancer-specific survival of TECDM patients with primary-tumor resection versus without primary-tumor resection stratified by therapies in the overall cohort.\u003c/p\u003e","description":"","filename":"Onlinefigu5.png","url":"https://assets-eu.researchsquare.com/files/rs-4930346/v1/aa455c7fabfdefee4bfc5753.png"},{"id":74858448,"identity":"424c18b9-c242-42e4-98c3-9f760df9e98a","added_by":"auto","created_at":"2025-01-27 16:09:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1426164,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4930346/v1/1e6a1205-fdff-48e7-8508-73e8f46cde43.pdf"},{"id":66858320,"identity":"a8672143-e919-4417-950b-a2f5f2c9df93","added_by":"auto","created_at":"2024-10-17 08:07:23","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":26207,"visible":true,"origin":"","legend":"","description":"","filename":"STable1.Baselinecharacteristicsoftheselectedpatientsbeforeandafterpropensityscorematching..docx","url":"https://assets-eu.researchsquare.com/files/rs-4930346/v1/3f3c8f4dac440899738a8b0e.docx"},{"id":66859830,"identity":"e1525486-48cc-4100-8008-95c34f37e37f","added_by":"auto","created_at":"2024-10-17 08:15:23","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":29485,"visible":true,"origin":"","legend":"","description":"","filename":"STable2.UnivariateandmultivariateanalysisofprognosticfactorsforOSintheoverallcohort.docx","url":"https://assets-eu.researchsquare.com/files/rs-4930346/v1/713346270d6435a82b9e37e2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Improved Survival of Primary-Tumor Resection in Metastatic Thoracic Esophageal Cancer: A Population-Based, Propensity Score Matched Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEsophageal cancer(EC), the ninth most common malignancy, is the sixth leading cause, globally, of malignant tumor deaths (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Due to lack of consistent and effective early screening algorithms, most esophageal cancer patients were diagnosed at local advanced stage and some of them were even diagnosed with distant metastases (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). For patients with distant metastases, treatment were usually limited to systemic chemotherapy or best supportive care according to patients\u0026rsquo; performance status. And local therapies such as radiation or palliative resection of primary tumor could be considered to improve quality of life or reduce the esophageal cancer relative symptoms such as obstruction or bleeding for metastatic esophageal cancer patients (\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, it was reported that metastatic esophageal cancer patients who underwent palliative esophagectomy had a better survival than those without esophagectomy (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). But after esophagectomy, distant metastatic recurrence frequently occurs (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Consequently, whether primary-tumor resection improves the prognosis of metastatic esophageal cancer patient remains controversial.\u003c/p\u003e \u003cp\u003eThe aim of this present study is to assess the survival effect of primary-tumor resection in TECDM patients.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics\u003c/h2\u003e \u003cp\u003eIn the present study, total 9680 thoracic esophageal cancer patients with distant metastasis, diagnosed with histologically confirmation, between 2010 and 2020 were collected from the SEER database. Under the inclusion criteria and exclusion criteria, 7733 patients were included in our study (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Of those patients, 121 patients underwent primary-tumor resection whereas 7612 patients did not. The baseline clinical and pathological characteristics of the included patients are showed in Supplementary Table\u0026nbsp;1. To balance the possible covariates such as diagnosis year, age, gender, race, marital status at diagnosis, median household income, differentiation of tumor, T stage of tumor, N stage of tumor, histologically type, location of tumor, size of tumor, chemotherapy, radiotherapy between primary-tumor resection group and no-surgery group, a 1:1 Propensity Score Matched(PSM) analysis was performed. After PSM, the clinical and pathological characteristics is well-balanced in the matched cohort (Supplementary Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSurvival outcomes of primary-tumor resection before PSM\u003c/h2\u003e \u003cp\u003eKaplan-Meier analysis were performed to evaluate overall survival (OS) and cancer-specific survival (CSS) of TECDM patients with primary-tumor resection(PTR) before PSM, and the log-rank test was used to compare any survival differences between the two groups. The results showed that TECDM patients with PTR had a significantly better median OS( p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA) and CSS(p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB) than TECDM patients without PTR. The median OS of TECDM patients with PTR were 11.0 months (95% CI, 9 months to13 months) and of TECDM patients without PTR were 4 months (95% CI, 4 months to 5 months). And the median CSS of those TECDM patients underwent PTR and of those TECDM patients without PTR was 9.0 months (95% CI, 7 months to 11 months) and 4 months (95% CI, 4 months to 4 months), respectively. In addition, Cox proportional hazards regression model was used to identify independent prognostic factors for CSS and OS in overall cohort. Multivariate Cox model analysis in the overall cohort showed that PTR, diagnosis year, age, race, marital status at diagnosis, median household income, differentiation of tumor, T stage of tumor, N stage of tumor, histologically type, location of tumor, size of tumor, chemotherapy, radiotherapy were independent prognostic factors for CSS in TECDM patients(Supplementary Table\u0026nbsp;2). Multivariate Cox model analysis revealed that PTR, age, marital status at diagnosis, median household income, differentiation of tumor, T stage, histologically type, tumor size, chemotherapy, radiotherapy were independent prognostic factors for OS in TECDM patients(Supplementary Table\u0026nbsp;2). Interestingly, PTR was a protective factor of OS in TECDM patients (HR:0.5529; 95% CI, 0.4537 to 0.6738, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSurvival outcomes of primary-tumor resection after PSM\u003c/h2\u003e \u003cp\u003eIn the PSM cohort, TECDM patients with PTR also had a significantly better median OS (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC) and CSS(p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD) than TECDM patients without PTR. After PMS, the median OS of those TECDM patients underwent PTR and of those TECDM patients without PTR was 11.0 months (95% CI, 9 months to 13 months) and 7 months (95% CI, 5 months to 9 months), respectively. And the median CSS of those TECDM patients underwent PTR and of those TECDM patients without PTR was 9.0 months (95% CI, 7 months to 11 months) and 6 months (95% CI, 4 months to 9 months), respectively. Furthermore, Cox proportional hazards model was performed to confirm the prognostic significance of PTR in patients with thoracic esophageal cancer with distant metastasis. Furthermore, multivariate Cox analysis in the matched cohort showed that PTR was independent protective factors for OS (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) and CSS in TECDM.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analysis of survival outcomes of primary-tumor resection\u003c/h2\u003e \u003cp\u003eMultivariate Cox model analysis revealed that PTR, age, median household income, differentiation of tumor, T stage of tumor, histologically type, size of tumor, chemotherapy, radiotherapy were independent prognostic factors for OS in TECDM patients. Next, subgroup analysis was performed to further explore the impact of PTR on OS in TECDM patients. In the age subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in year\u0026thinsp;\u0026lt;\u0026thinsp;65 and year\u0026thinsp;\u0026gt;\u0026thinsp;65 subgroups(P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA); In median household income subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in income\u0026thinsp;\u0026gt;\u0026thinsp;60 000 and income\u0026thinsp;\u0026lt;\u0026thinsp;60 000 subgroups( P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB); In differentiation of tumor subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in GradeⅠ-Ⅱ and GradeⅢ-Ⅳ subgroups( P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC); In T stage of tumor subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in T1-T2 and T3-T4 subgroups( P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD); In histologically type subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in Squamous and Adenocarcinoma subgroups( P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eE); Also, in size of tumor subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in tumor size\u0026thinsp;\u0026gt;\u0026thinsp;5mm and \u0026lt;\u0026thinsp;5mm subgroups( P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eF).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSimilarly, subgroup analysis was performed to further explore the impact of other treatments on OS and CSS in TECDM patients. In chemotherapy subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in chemotherapy and no-chemotherapy subgroups( P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB); Besides, in radiotherapy subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR in radiotherapy and no-radiotherapy subgroups( P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eD).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThoracic esophageal cancer with distant metastasis(TECDM), as one of the severe fatal disease, is considered as an advanced esophageal cancer with poor long-term prognosis (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Neoadjuvant chemotherapy with or without radiotherapy followed by esophageal surgery is the cornerstone of locally advanced esophageal cancer treatment (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). But thoracic esophageal cancer with distant metastasis was unsuitable for primary tumor resection and recommended treatment for TECDM is systematic therapies (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). According to NCCN Clinical Practice Guideline, systemic therapy regimens were recommended for metastatic thoracic esophageal cancer. And with aim of relieving symptom and improving in quality of life, palliative supportive care in metastatic thoracic esophageal cancers is encouraged (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Similarly, the European Society for Medical Oncology (ESMO) Clinical Practice Guideline does not consider surgery as a treatment option for thoracic esophageal cancer patients with distant metastasis. And the recommended treatment is palliative chemotherapy (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Besides, the ESMO Clinical Practice Guidelines state that patients with metastatic esophageal cancer may be considered for different palliative care options such as external radiotherapy, gastrostomy, jejunostomy and metal stent insertion based on their clinical situation (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, considering the benefits of primary-tumor surgery for patients with colorectal cancer and liver metastases, an increasing number of surgeons are focusing on the role of primary tumor surgery in metastatic cancer patients (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). For metastatic esophageal cancer, a retrospective study have shown that primary-tumor surgery significantly improve survival in patients with TECDM (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). But limited by small samples and single center data, the survival benefit of primary- tumor surgery to thoracic esophageal cancer patients with distant metastases need to be further confirmed. In a word, primary-tumor resection in metastatic esophageal cancer remains controversial and debated.\u003c/p\u003e \u003cp\u003eIn our present study, total 121 patients from multiple centers in USA underwent esophageal primary tumor resection. As a result, primary-tumor resection, an independent prognostic factor, improves overall survival and cancer-specific survival of the thoracic esophageal cancer patients with distant metastasis. First of all, using the SEER data of demographics and survival information, the study showed that great improvements of OS and CSS for TECDM patients with primary-tumor resection in overall cohort. What is more, after Propensity Score Matching, aiming to balance the possible covariates between PTR group and no-PTR group, PTR improves overall survival and cancer-specific survival of the thoracic esophageal cancer patients with distant metastasis in PSM cohort. And multivariate Cox model analysis revealed that PTR, age, median household income, differentiation of tumor, T stage of tumor, histologically type, size of tumor, chemotherapy, radiotherapy were independent prognostic factors for OS in TECDM patients. Last but not the least, in all subgroups, the median OS and median CSS of TECDM patients with primary-tumor resection was better than the patients without PTR.\u003c/p\u003e \u003cp\u003eThe results align with previous retrospective studies in other metastatic gastric, ovarian, kidney and neuroendocrine tumors, primary- tumor resection can lead to the better survival (\u003cspan additionalcitationids=\"CR19 CR20 CR21\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). We used propensity score matched (PSM) analysis to reduce the possible influence of some potential covariates, between primary-tumor resection group and no-surgery group, that might distort the real relation of primary-tumor resection with CSS and OS. In other words, our study minimized the selection bias of patients to receive PTR. Besides, the present studies focused specifically on metastatic thoracic esophageal cancer patients that are more suitable for surgical resection than other sites.\u003c/p\u003e \u003cp\u003eWhy primary-tumor surgery is able to prolong the survival of tumor patients with metastasis remains unclear. It was reported that one possible mechanism that primary-tumor resection decreased circulating tumor cells of the blood contributing to distant metastases (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Besides, primary-tumor resection might recover the immune system to prolong the survival of patients with metastatic tumor (\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Hence, in the present study, primary-tumor resection might improve overall survival and cancer-specific survival of the thoracic esophageal cancer patients with distant metastasis by decreasing circulating tumor cells of the blood and restoring the function of immune system.\u003c/p\u003e \u003cp\u003eHowever, some opponents consider that primary-tumor resection might accelerate metastasis, which is related to the angiogenesis and growth of metastases after primary tumor resection (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Additionally, primary-tumor resection for patients with metastatic esophageal cancer does not significantly improve five-year survival, but increase preoperative or postoperative complications and thus delay systemic therapy (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Besides, primary-tumor resection increases medical costs and might lead to low quality of life after surgery (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Consequently, the multidisciplinary team should assess whether thoracic esophageal cancer patients with distant metastasis are suitable for resection of primary tumor.\u003c/p\u003e \u003cp\u003eThere are also some limitations in the present study. First of all, the present study, as a retrospective research, has its natural limitation of selection bias. Consequently, propensity score matched (PSM) was used to reduce the possible confounding bias between the PTR group and no-PTR group, making our conclusions more reliable. What is more, due to limitation of incomplete information from SEER database, some information such as performance status is unreported. Therefore, well-designed randomized control trials should be performed to verify our findings.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, the retrospective study showed that primary-tumor resection is associated with good overall survival and cancer-specific survival in thoracic esophageal cancer patients with distant metastasis.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eData source and patients selection\u003c/h2\u003e \u003cp\u003eThe SEER*Stat software (version 8.4.3) was used to download detailed information including patient demographics and survival information. All thoracic esophageal cancer patients with distant metastasis(TECDM) at diagnosis between the years 2010 and 2020 were identified(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Firstly, thoracic esophageal cancer patients with distant metastasis were retrieved using the Primary Site - labeled value{Site - labeled = 'C15.1-Thoracic esophagus', 'C15.3-Upper third of esophagus', 'C15.4-Middle third of esophagus', 'C15.5-Lower third of esophagus', 'C15.8-Overlapping lesion of esophagus'}. Secondly, TECDM with microscopically diagnosed at diagnosis between the years 2010 and 2020 were selected. The inclusion criteria were as follows: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) diagnosed with esophageal cancer only; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)confirmed distant metastases; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) diagnosed with histologically confirmation; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) treatment information of primary tumor was known. The exclusion criteria were as follows: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) patients diagnosed with over one primary tumor; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) treatment information of primary tumor was unknown. Thirdly, demographics and survival information was collected as followed: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)diagnosis year; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)age; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)gender; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)race record; (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)marital status at diagnosis; (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) median household income; (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) residence record; (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)PRCDA record; (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) reporting source; (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) differentiation of tumor; (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) T stage; (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)N stage; (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) histologically type; (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)tumor location; (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)tumor size (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)Chemotherapy; (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) Radiotherapy; (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) resection of primary tumor; (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) survival months; (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)Vital status record.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePropensity Score Matched (PSM)\u003c/h2\u003e \u003cp\u003ePropensity score matched (PSM) was used to reduce the possible influence of potential covariates between primary-tumor resection group and no-surgery group. With the nearest neighbor matched method of setting caliper value 0.1, included patients were matched 1:1 into primary-tumor resection and no-surgery group. In the present study, the covariates used for PSM were as follows: diagnosis yea, age record, gender, race record, marital status at diagnosis, median household income, differentiation of tumor, T stage of tumor, N stage of tumor, histologically type, location of tumor, size of tumor, Chemotherapy, Radiotherapy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe chi-square test was performed to compare categorical variables in the present study with the aims of revealing any differences of clinical and pathological characteristics between the primary-tumor resection group and no-surgery group. Kaplan-Meier analysis was performed to evaluate overall survival (OS) and cancer-specific survival (CSS) of TECDM patients with primary tumor resection(PTR) before and after PSM, and the log-rank test was used to compare any survival differences between the primary-tumor resection group and no-surgery group. Cox proportional hazards regression model was used to identify independent prognostic factors for CSS and OS in our study. Variables with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in the univariate Cox model were further put into the multivariate Cox model analysis. All statistical analyses in the present study were performed using R software(version 4.3.1 ), and a two sided P value less than 0.05 was considered statistical significance.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEthics Statement\u003c/h2\u003e \u003cp\u003e Approval of the study was given by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University(2023ZSLYEC-342). This study strictly complied with the Declaration of Helsinki, and all data in the present study was obtained from the SEER database with no need for informed patient consent.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflicts of Interest:\u003c/h2\u003e \u003cp\u003eAll authors declare no conflict of interest.\u003c/p\u003e \u003ch2\u003eData Sharing Statement\u003c/strong\u003e \u003cp\u003eThe datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\u003ch2\u003eFunding statement:\u003c/h2\u003e \u003cp\u003eThis work was supported by National Key Clinical Discipline \u0026amp; the National Natural Science Foundation of China [grant number 82102955] \u0026amp; No.2: the Guangzhou Basic Research Project [grant number 202201011326].\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJY W, XY Q , GF W and HS z wrote the main manuscript text; F Q, Z L, BZ J, YZ Z, JG C and HY L prepared figures 1-5. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSung, H. et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. \u003cem\u003eCA Cancer J. Clin.\u003c/em\u003e \u003cb\u003e71\u003c/b\u003e, 209\u0026ndash;249. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3322/caac.21660\u003c/span\u003e\u003cspan address=\"10.3322/caac.21660\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBray, F. et al. 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The influence of local therapy on the survival of patients with metastatic rectal cancer: a population-based, propensity-matched study. \u003cem\u003eJ. Cancer Res. Clin. Oncol.\u003c/em\u003e \u003cb\u003e143\u003c/b\u003e, 1891\u0026ndash;1903. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00432-017-2442-2\u003c/span\u003e\u003cspan address=\"10.1007/s00432-017-2442-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"esophageal cancer, distant metastasis, primary-tumor resection, prognosis, SEER","lastPublishedDoi":"10.21203/rs.3.rs-4930346/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4930346/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe study aims to assess the survival effect of primary-tumor resection (PTR) on thoracic esophageal cancer with distant metastasis(TECDM). Data of patients with TECDM was collected from the Surveillance, Epidemiology, and End Results database from 2010 to 2020. We used a 1:1 propensity-score matching(PSM) analysis to minimize heterogeneity between different groups. Total 7733 patients with TECDM were included, and 121 patients and 7612 patients underwent primary-tumor resection and did not, respectively. Patients underwent primary-tumor resection had a better median OS and median CSS than those patients did not in overall and PSM cohort. In PSM cohort, the median OS was 11 months (95% CI, 9 months to 13 months) for TECDM patients with PTR and 7 months (95% CI, 5 months to 9 months) for those patients without PTR. Additionally, cox proportional hazard models similarly indicated that PTR was a significantly protective factor for TECDM patients in OS (HR: 0.5529; 95% CI, 0.5196 to 0.7730, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and CSS (HR:0.5869 ; 95% CI, 0.479 to 0.7192, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In conclusion, primary-tumor resection prolongs survival of thoracic esophageal cancer patients with distant metastasis.\u003c/p\u003e","manuscriptTitle":"Improved Survival of Primary-Tumor Resection in Metastatic Thoracic Esophageal Cancer: A Population-Based, Propensity Score Matched Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-17 08:07:18","doi":"10.21203/rs.3.rs-4930346/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-25T09:41:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-24T11:43:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"214548120098257609080841511442090611520","date":"2024-11-12T07:32:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-19T13:29:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"313468315994271605017928038375414415968","date":"2024-10-09T11:04:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-04T22:53:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-04T22:52:34+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-29T13:26:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-27T10:56:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-08-17T14:56:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"62d28373-c232-409e-84e2-dbfa84d8d8f3","owner":[],"postedDate":"October 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":37353341,"name":"Biological sciences/Cancer/Lung cancer"},{"id":37353342,"name":"Health sciences/Oncology/Surgical oncology"}],"tags":[],"updatedAt":"2025-01-27T16:02:24+00:00","versionOfRecord":{"articleIdentity":"rs-4930346","link":"https://doi.org/10.1038/s41598-025-85419-y","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-01-24 15:57:43","publishedOnDateReadable":"January 24th, 2025"},"versionCreatedAt":"2024-10-17 08:07:18","video":"","vorDoi":"10.1038/s41598-025-85419-y","vorDoiUrl":"https://doi.org/10.1038/s41598-025-85419-y","workflowStages":[]},"version":"v1","identity":"rs-4930346","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4930346","identity":"rs-4930346","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}