Long-term outcomes after curative endoscopic submucosal dissection vs. gastrectomy in late elderly patients aged ≥75 years with early gastric cancer

Long-term outcomes after curative endoscopic submucosal dissection vs. gastrectomy in late elderly patients aged ≥75 years with early gastric cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Long-term outcomes after curative endoscopic submucosal dissection vs. gastrectomy in late elderly patients aged ≥75 years with early gastric cancer Seung Han Kim, Seon-Young Park, Hyunsoo Chung, Chung Hyun Tae, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7689469/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract This study compares outcomes of endoscopic submucosal dissection (ESD) with those of gastrectomy in late elderly patients aged ≥75 years with early gastric cancers (EGCs) that meet the curative resection criteria. We included 4,241 elderly EGC patients treated with either ESD (n=4,083) or gastrectomy (n=158) between 2010 and 2020. The primary outcome was overall survival (OS), and was investigated in the overall cohort and the 4-to-1 propensity score (PS)-matched cohort. During a median follow-up of 6.6 years, the 5-year OS rates were 84.8% and 82.9% in the ESD and surgery groups, respectively; and the OS did not differ between the two groups in the overall and PS-matched cohorts (all P> 0.05 by the log-rank test). In the PS-matched cohort, the multivariate analyses showed that ESD was not a risk factor for overall mortality (adjusted hazard ratio, 0.77; 95% confidence interval, 0.57–1.04). The ESD group had fewer adverse events (AEs) (7.6% vs. 12.0%; P=0.044) than the surgery-group. In conclusion, long-term outcomes after ESD were comparable to those after gastrectomy in EGCs meeting the curative resection criteria with acceptable treatment-related AEs in late elderly EGC patients. Biological sciences/Cancer Health sciences/Gastroenterology Health sciences/Oncology Elderly Early gastric cancer Endoscopic submucosal dissection Gastrectomy Figures Figure 1 Figure 2 Introduction Gastric cancer is an age-related disease; it was detected in about two-thirds of patients aged ≥ 65 years. 1 In Eastern Asian countries, including Korea, Japan, and China, the incidence of gastric cancer (GC) is the highest in the late elderly aged ≥ 75 years. 2 , 3 Because of multiple comorbidities that can affect outcomes, the decision for GC treatment is challenging in late elderly GC patients. 4 , 5 Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early GCs (EGCs) that meet curative resection criteria. 6 , 7 Additionally, ESD is a feasible treatment with acceptable long-term outcomes in EGC patients. 8 – 10 Given the high GC incidence, the number of elderly patients with EGC who could undergo ESD has increased. A previous meta-analysis involving 18 retrospective studies reported that long-term overall survival (OS) after curative ESD of EGCs was comparable to that after gastrectomy. 11 Previous studies evaluating the long-term ESD outcomes compared to outcomes after gastrectomy have been conducted in younger GC patients (aged < 70 years). 11 Like the results in previous studies involving younger patients, comparable OS between ESD and gastrectomy has been reported in elderly EGC patients aged ≥ 70 years. 12 – 15 However, previous studies included a small number of patients who underwent ESD (< 60 patients), 12, 13 short follow-up periods (median follow-up of 50%).(15) The outcome comparisons between ESD and gastrectomy in late elderly EGC patients need to be investigated, including the patients with curative resection ESD criteria and long-term follow-up periods. For the EGCs that met the curative resection criteria for ESD, our study evaluated whether ESD was an acceptable treatment in late elderly EGC patients aged ≥ 75 years compared with gastrectomy. Methods Patients Our study was a multicenter retrospective study. EGC patients aged ≥ 75 years who underwent ESD in 22 hospitals or gastrectomy in two hospitals from January 2011 to December 2020 were included. The patients had EGC lesions that met the curative ESD criteria on the final pathological evaluations after ESD or gastrectomy according to the GC treatment guideline (Table S1 ). 6 Patients were excluded if their ESD results were noncurative, if they had a history of gastrectomy, or if they had incomplete information on follow-up status after treatment. This study was approved by the Institutional Review Board (IRB) of Pusan National University Hospital (IRB number 2309-031-131) and each of the other participating hospitals. Informed signed consents from the patients were waived by the IRB because of the minimal risk of this study. This study was conducted in accordance with the principles of the Declaration of Helsinki. Endoscopic submucosal dissection procedure, gastrectomy, and pathological evaluation An experienced endoscopist qualified by the Korean Society of Gastrointestinal Endoscopy had performed ESD, including lesion marking, precutting outside the marking, and submucosal dissection, with hemostasis for all non-bleeding visible vessels on the ESD ulcer bed. Surgical treatment consisted of radical gastrectomy and lymph node (LN) dissection, according to the GC treatment guideline. 6 Depending on the GC location, experienced surgeons performed total, pylorus-preserving, proximal, or distal gastrectomy. The resected EGC specimens were fixed and immersed in 10% neutral buffered formalin for preparing paraffin blocks. The section intervals of ESD and gastrectomy specimens were 2 mm and 4–5 mm, respectively. 16 The sliced specimens were embedded in paraffin, and hematoxylin/eosin-stained 5-µm sections of each paraffin block were evaluated by specialized gastrointestinal pathologists. Follow-up after early gastric cancer treatment For patients curatively treated with ESD and gastrectomy, patients were followed up with endoscopy and abdominal computed tomography every 6 months for the first 2–3 years and then annually until 5 years after treatment. Study outcomes The primary outcome was OS. Secondary outcomes were disease-specific survival (DSS) and GC recurrence. The event for OS was death from any cause whereas the event for DSS was death from GC or GC recurrence. Other outcomes included treatment-related adverse events (AEs) including death, and risk factors associated with overall mortality and GC recurrence. GC recurrence included local or distant recurrence, metachronous recurrence (GC occurring in the remnant stomach at one year or later after treatment). We collected data on deaths and GC recurrence until February 2025. Statistical analysis Analyses of descriptive data were conducted using the independent t test or Mann–Whitney U test for continuous variables and the chi-square or Fisher exact test for categorical variables. In this study, a propensity score (PS) matched analysis was performed to reduce selection bias between the treatment groups. A logistic regression model was used to estimate the PSs by including the following variables that could affect the outcomes of ESD and surgery: age, sex, comorbid illnesses (diabetes mellitus, hypertension, cardiovascular disease, and cerebrovascular disease), American Society of Anesthesiologists physical status (ASA) score, tumor characteristics (tumor size, depth, ulcer, histologic type), and curative ESD resection criteria (absolute vs. expanded criteria). A 4:1 nearest-neighbor matching was performed with a caliper of 0.2. Survival curves were obtained using the Kaplan–Meier method. To compare the survival outcomes, we used the log-rank test for OS and Gray’s test for DSS and GC recurrence. The evaluation of risk factors for overall mortality and GC recurrence were performed using the Cox proportional hazard regression model and the Fine–Gray regression model, 17 respectively. We used STATA 18.0 (StataCorp, College Station, TX, USA) and R version 4.4.3 for statistical analyses, and a P -value of < 0.05 was considered significant. Results Patient and GC characteristics The detailed study flow is summarized in Fig. 1 . Totally 1,640 patients were excluded from the final cohort because of noncurative resection on the final pathological evaluation, previous gastrectomy history, and incomplete information on follow-up status. Finally, 4,120 patients who underwent ESD (ESD group) and 158 who underwent gastrectomy (surgery group) were included (overall cohort). After PS-matching (PSM), 632 patients in the ESD group and 158 in the surgery group were included in the PSM cohort). Baseline clinical and GC characteristics of the overall and PS-matched cohorts were described in Table 1 . The mean patient age in the overall cohort was 78.7 years. The ESD group had a significantly older (mean age, 78.7 years vs. 78.0 years; P = 0.011) and a larger proportion of male patients (66.2% vs. 58.2%; P = 0.037) than the surgery group. The proportion of hypertension and chronic lung disease was lower in the ESD group, but patients with ASA score ≥ 3 were larger in the ESD group than in the surgery group (23.3% vs. 18.4%; P < 0.001). Regarding tumor characteristics, the ESD group had a larger proportion of tumors with undifferentiated histologic type, lower 1/3 location, and absolute criteria, whereas the surgery group had a larger tumor size and a more proportion of tumors with ulcers. In the PSM cohort, the clinical and GC characteristics between the two groups were well balanced, with a standardized mean difference of < 0.2. Table 1 Patient and tumor characteristics Overall cohort P SMD Propensity score-matched cohort P SMD ESD Surgery ESD Surgery (no = 4,083) (no = 158) (no = 632) (no = 158) Age (year), mean ± SD 78.7 ± 3.3 78.0 ± 2.8 0.011 0.219 78.5 ± 3.1 78.0 ± 2.8 0.056 0.175 Sex, no (%) 0.037 0.166 0.828 0.019 Female 1,379 (33.8) 66 (41.8) 258 (40.8) 66 (41.8) Male 2,704 (66.2) 92 (58.2) 374 (59.2) 92 (58.2) Co-morbid illnesses, no (%) Hypertension 2,450 (60.0) 114 (72.2) 0.002 0.259 399 (63.1) 114 (72.2) 0.034 0.194 Diabetes mellitus 1,036 (25.4) 39 (24.7) 0.845 0.016 162 (25.6) 39 (24.7) 0.806 0.022 Cardiovascular disease 556 (13.6) 14 (8.9) 0.085 0.151 74 (11.7) 14 (8.9) 0.309 0.094 Cerebrovascular disease 323 (7.9) 11 (7.0) 0.664 0.036 67 (10.6) 11 (7.0) 0.170 0.129 Chronic liver disease 67 (1.6) 0 (0) 0.180 0.183 11 (1.7) 0 (0) 0.134 0.188 Chronic lung disease 236 (5.8) 16 (10.1) 0.023 0.161 34 (5.4) 16 (10.1) 0.028 0.178 Chronic kidney disease 306 (7.5) 12 (7.6) 0.962 0.004 56 (8.9) 12 (7.6) 0.612 0.046 Other malignancy 354 (8.7) 9 (5.7) 0.190 0.115 57 (9.0) 9 (5.7) 0.177 0.128 ASA PS score, no (%) < 0.001 0.636 < 0.001 0.571 1 674 (16.5) 1 (0.63) 92 (14.6) 1 (0.63) 2 2,458 (60.2) 128 (81.0) 403 (63.8) 128 (81.0) 3 or higher 951 (23.3) 29 (18.4) 137 (21.7) 29 (18.4) Tumor histologic type, no (%) < 0.001 0.546 0.032 0.18 Differentiated type 4,001 (98.0) 130 (82.3) 560 (88.6) 130 (82.3) Undifferentiated type 82 (2.0) 28 (17.7) 72 (11.4) 28 (17.7) Tumor size (mm), mean ± SD 16.5 ± 10.4 27.0 ± 17.1 < 0.001 0.738 24.3 ± 15.1 27.0 ± 17.1 0.055 0.164 Tumor location, no (%) < 0.001 0.329 Lower 1/3 2,979 (73.0) 96 (60.8) 436 (69.0) 96 (60.8) 0.083 0.196 Middle 1/3 788 (19.3) 53 (33.5) 156 (24.7) 53 (33.5) Upper 1/3 316 (7.7) 9 (5.7) 40 (6.3) 9 (5.7) Tumor depth, no (%) 0.803 0.02 0.304 0.096 Mucosa 3,844 (94.1) 148 (94.1) 576 (91.1) 148 (93.7) SM1 239 (5.9) 10 (6.3) 56 (8.7) 10 (6.3) Presence of ulcer, no (%) 194 (4.8) 23 (14.6) < 0.001 0.337 111 (17.6) 23 (14.6) 0.368 0.082 Curative resection criteria, no (%) < 0.001 1.156 0.962 0.004 Absolute 2,713 (66.4) 27 (17.1) 109 (17.2) 27 (17.1) Expanded 1,370 (33.6) 131 (82.9) 523 (82.8) 131 (82.9) Abbreviations: ESD, endoscopic submucosal dissection; SMD, standardized mean difference; SD, standard deviation; ASA PS, American Society of Anesthesiologist Physical Status; SM, submucosa. Comparison of long-term outcomes A median follow-up was 6.6 years (interquartile range [IQR], 4.6–8.9 years), and the 5-year OS rates were 84.8% in the ESD group and 82.9% in the surgery group. No differences in the OS were observed between the ESD and surgery groups in the overall cohort ( P = 0.396) (Fig. 2 A) or in the PSM cohort ( P = 0.248) (Fig. 2 B). Seven GC-related deaths were observed in the ESD group. Of the patients who died of GC, three received systemic chemotherapy for extra-gastric recurrence, and four (two extra-gastric recurrences and two metachronous recurrences) were observed without treatment for the recurrence. In the overall cohort, DSS rates were not different between the two treatment groups (5-year DSS rates, 99.8% vs. 100%, respectively; P = 0.554). No GC-related deaths were observed in PSM cohort. In the overall cohort, GC recurrence occurred in 248 patients (6.1%, 248 of the 4,083 patients; 190 metachronous recurrences, 52 local recurrences, and 6 extra-gastric recurrences) in the ESD group and one patient (0.6%, 1 of the 158 patients; 1 extra-gastric recurrence) in the surgery group (Table S2). Most of the patients with local (88.5%) and metachronous recurrences (93.7%) were treated by endoscopic therapy or surgical treatment. The 5-year incidences of GC recurrence were 9.3% in the ESD group and 0.7% in the surgery group, and the ESD group had a significantly higher incidence of GC recurrence compared to the surgery group ( P < 0.001) (Fig. 2 C). Similarly, in the PSM cohort, the ESD group had a greater GC recurrence than the surgery group ( P < 0.001) (Fig. 2 D). Risk factors for the overall mortality and GC recurrence Risk factors for overall mortality and GC recurrence were evaluated in the PSM cohort. In the univariate analyses, significant risk factors for overall mortality were age of 80 ~ 84 years and ≥ 85 years; male sex; chronic liver disease, chronic kidney disease, and other malignancies; and, a higher ASA score (2 and ≥ 3) (Table S3). In the multivariate analysis, the overall mortality after ESD (adjusted hazard ratio [aHR], 0.77; 95% confidence interval [CI], 0.57–1.04) was not different from that after surgery (Table 2 ). Age of 80 ~ 84 years (aHR, 1.98; 95% CI, 1.48–2.63) and ≥ 85 years (aHR, 3.82; 95% CI, 2.39–6.10), male sex (aHR, 1.55; 95% CI, 1.18–2.04), presence of other malignancy (aHR, 1.63; 95% CI, 1.07–2.48), and ASA score 2 (aHR, 1.81; 95% CI, 1.07–3.05) were the significant risk factors for overall mortality. Table 2 Risk factors associated with overall mortality and gastric cancer recurrence in multivariate analyses* Overall mortality† Gastric cancer recurrence‡ Total no. aHR 95% CI P aHR 95% CI P Treatment Surgery 158 1.00 1.00 ESD 632 0.77 0.57–1.04 0.088 19.29 2.47-150.98 0.005 Age group 75 ~ 79 years 545 1.00 1.00 80 ~ 84 years 206 1.98 1.48–2.63 < 0.001 1.14 0.53–2.43 0.737 85 years ~ 39 3.82 2.39–6.10 < 0.001 0.99 0.89–1.10 0.867 Sex Female 324 1.00 Male 466 1.55 1.18–2.04 0.002 Chronic liver disease 11 2.22 0.99–4.98 0.054 Chronic kidney disease 68 1.15 0.75–1.75 0.525 Other malignancy 66 1.63 1.07–2.48 0.023 ASA score 1 93 1.00 2 531 1.81 1.07–3.05 0.027 3 or higher 166 1.46 0.81–2.62 0.207 Abbreviations: ESD, endoscopic submucosal dissection; aHR, adjusted hazard ratio; CI, confidence interval. *The analyses were performed in the propensity score-matched cohort. †The Cox-proportional hazard regression model was used to evaluate risk factors for the overall mortality. ‡The Fine-Gray regression model was used to evaluate risk factors for the gastric cancer recurrence. For GC recurrence, ESD treatment and higher age groups of 80 ~ 84 years and ≥ 85 years were significant risk factors in univariate analyses (Table S3). The risk of GC recurrence was significantly greater in the ESD group (aHR, 19.29; 95% CI, 2.47–150.98) than in the surgery group (Table 2 ). Hospital stays and treatment related AEs The hospital duration for EGC treatment was shorter in the ESD group than that in the surgery group (median, 4 days vs. 10 days, respectively; P < 0.001) (Table 3 ). Total treatment-related AEs (7.6% vs. 12.0%, P = 0.044) and AEs requiring surgical treatment (0.1% vs. 1.3%, P = 0.026) were less frequent in the ESD group than in the surgery group. In the surgery group, two patients (1.3%) died of treatment-related AEs (one died due to septic shock after developing anastomotic leakage and one due to septic shock caused by intestinal obstruction after postoperative adhesion). No deaths due to treatment-related AEs were observed in the ESD group. Table 3 Hospital stays and treatment related adverse events Treatment group P ESD Surgery (no = 4,083) (no = 158) Hospital stays (days), median (IQR) 4 (4–5) 10 (7–12) < 0.001 Adverse events Total patients with adverse events, no (%) 312 (7.6) 19 (12.0) 0.044 Details of adverse events, no Bleeding 237 1 Perforation 60 0 Pneumonia 29 4 Ileus or intestinal obstruction 0 5 Anastomotic leakage 0 5 Intraabdominal fluid collection 0 3 Anastomotic stricture 0 1 Wound dehiscence 0 1 Liver failure 0 1 Pulmonary thromboembolism 0 1 Adverse events requiring surgery, no (%) 5 (0.1) 2 (1.3) 0.026 Death due to adverse event, no (%) 0 (0) 2 (1.3) 0.001 Abbreviations: ESD, endoscopic submucosal dissection; IQR, interquartile range. Discussion This multi-center retrospective cohort study showed that the long-term OS after ESD was comparable to that after gastrectomy for EGC meeting the curative resection criteria of ESD in late elderly EGC patients aged ≥ 75 years. Due to the higher rate of local or metachronous recurrence, the ESD group had a higher incidence of GC recurrence than the surgery group. However, most of the local and metachronous recurrences after ESD were treated endoscopically. In addition, the ESD group had shorter hospital stays and fewer treatment-related AEs than the surgery group. Given that > 70% of late elderly persons aged ≥ 75 years had multiple comorbid illnesses, 18 minimally invasive treatments were preferred options to reduce treatment-related morbidity and mortality. In Korea and Japan, where the nationwide gastric cancer screening program was implemented, >50% of newly diagnosed GCs were in the localized stage, 19, 20 and the number of elderly GC patients indicated for ESD at the diagnosis has increased. In late elderly EGC patients aged ≥ 75 years, ESD was technically feasible with the R0 resection rate of > 90% and acceptable treatment-related AEs. 21 – 23 Although previous studies have reported that the OS after ESD was comparable to that after gastrectomy in elderly EGC patients, 12–14 in the previous studies, long-term survival outcomes were evaluated in patients with both curative and noncurative ESD. In elderly EGC patients with noncurative ESD, survival outcomes were affected by whether they underwent additional gastrectomy or not. 24 For proper comparisons of survival outcomes, our study included only patients with EGCs that met the curative resection criteria of ESD to investigate the outcomes after ESD compared to those after gastrectomy. In our study, survival outcomes after ESD for late elderly patients with EGCs meeting the curative resection criteria were favorable, with a 5-year OS of 84.8% and DSS rate of 99.8%. In addition, the survival rates after ESD were comparable to those after gastrectomy in the overall and PSM cohorts, which was consistent with the findings of previous studies involving younger patients with EGC that compared outcomes between ESD and gastrectomy for GCs meeting curative resection criteria. 8 – 10 In our study, although older age (80 to 84 years and > 85 years), presence of other malignancies, and ASA score 2 were risk factors for overall mortality in a multivariate analysis, the outcomes were not affected by treatment modality (ESD vs. gastrectomy) and curative resection criteria (absolute vs. expanded). These findings suggest that ESD is a primary treatment option over gastrectomy in late elderly EGC patients who have EGCs that meet the ESD curative resection criteria. Because of stomach preservation, metachronous recurrence was the main pattern of GC recurrence after curative ESD for EGCs, whereas extra-gastric recurrence was rare. 8 – 10 The recurrence patterns were similar in elderly patients with EGC. 14 , 23 Due to metachronous recurrence after ESD, a higher GC recurrence rate was observed after ESD compared to gastrectomy. 8 – 10 , 14 , 23 Our study also reported a higher GC recurrence in the ESD group than in the surgery group, mainly because of local or metachronous recurrence after ESD. Like the previous studies involving younger or elderly patients with EGC, the majority of the local (71%) or metachronous (84%) cancers were successfully treated with endoscopic therapy. Thus, elderly patients with EGC who underwent ESD should be provided Helicobacter pylori therapy to prevent metachronous recurrence and undergo long-term endoscopic surveillance to detect cancer recurrence at earlier stages like in younger EGC patients, according to guideline recommendations. 25 – 27 Treatment-related AEs are another major concern in the treatment of EGCs in late elderly patients because many elderly patients have multiple comorbid illnesses. Due to poor nutritional status and pulmonary dysfunction, elderly patients with GC who underwent gastrectomy had significantly greater rates of anastomotic leakage and postoperative pneumonia than those in younger patients. 28 , 29 Previous studies comparing the outcomes of gastrectomy and ESD for EGCs also reported higher treatment-related AEs in patients who underwent gastrectomy, particularly late AEs occurring > 30 days after treatment requiring endoscopic or surgical management. 8 , 9 In studies involving elderly patients with EGC, the surgery group had higher AEs requiring intensive care unit admission and severe organ dysfunction (e.g., pneumonia and kidney injury) during the short-term postoperative period. 13 , 14 Rates of ESD related AEs were 8–12%, and bleeding and perforation were major ESD-related AEs that could be treated with conservative or endoscopic therapy. 13 , 14 , 21 , 23 In our study, patients who underwent ESD had less frequent total treatment-related AEs and AEs requiring surgery than those who underwent surgery. In addition, no treatment-related death was observed. The duration of the hospital stay was shorter in the ESD group than that in the surgery group. The findings provided robust evidence that ESD can be safely performed in elderly EGC patients, considering treatment-related AEs and mortality. This study evaluated the oncologic outcomes after ESD vs. gastrectomy in many late elderly EGC patients aged ≥ 75 years (> 4,000 patients) during long-term follow-up. However, this study has several limitations. First, our study was a retrospective cohort study, and selection bias was unavoidable. To reduce bias, we evaluated outcomes in all patients and in the PSM cohort. In addition, a prospective randomized controlled trial may be unethical because ESD is the accepted treatment for EGCs meeting the guideline indication. Second, the risk factors associated with metachronous GC, including H. pylori infection gastric atrophy, and intestinal metaplasia, were not evaluated in this study because it mainly focused on long-term oncologic outcomes. Third, the patient number in the surgery group was smaller than that in the ESD group, owing to the limited availability of surgical data. In conclusion, for late elderly GC patients aged ≥ 75 years, long-term OS and DSS after ESD were comparable to those after gastrectomy for EGCs meeting the curative resection criteria of ESD. Even though a higher risk of GC recurrence was observed after ESD, mainly due to local or metachronous recurrence, most of these were manageable by endoscopic treatment. Considering the lower number of severe treatment-related AEs and higher prevalence of comorbid illnesses in late elderly patients with EGC, ESD might be a preferred primary treatment option over gastrectomy for EGCs meeting both absolute and expanded indications. Declarations Conflicts of interest : The authors declare no conflicts of interest. Funding declaration : Korean College of Helicobacter and Upper Gastrointestinal Research Foundation: grant number KCHUGR-202302501 National Cancer Center: grant number 2310680 and 2311480 Author contributions: Seung Han Kim: data acquisition, drafting of article, critical revision for important intellectual content, and final approval of the manuscript Seon-Young Park: data acquisition, drafting of article, critical revision for important intellectual content, and final approval of the manuscript Hyunsoo Chung: guarantor of the article, data acquisition, drafting of article, critical revision for important intellectual content, and final approval of the manuscript Chung Hyun Tae: data acquisition, critical revision for important intellectual content, and final approval of the manuscript Hyeong Ho Jo: data acquisition, critical revision for important intellectual content, and final approval of the manuscript Jeong Hoon Lee: data acquisition, critical revision for important intellectual content, and final approval of the manuscript Ayoung Lee: data acquisition, critical revision for important intellectual content, and final approval of the manuscript Jae Myung Park: data acquisition, critical revision for important intellectual content, and final approval of the manuscript Hwoon-Yong Jung: data acquisition, critical revision for important intellectual content, and final approval of the manuscript Young-Il Kim: guarantor of the article, conception and design of the study, data acquisition and interpretation, drafting of article, critical revision for important intellectual content, and final approval of the manuscript. Ethics statement This study was approved by the Institutional Review Board (IRB) of Pusan National University Hospital (IRB number 2309-031-131) and each of the other participating hospitals. Informed signed consents from the patients were waived by the IRB because of the minimal risk of this study. Acknowledgement A list of the Korean elderly ESD study group is provided in the supplementary material. Data availability statement The data used in the current study are available from the corresponding author (YI Kim) on reasonable request after approval of the ethics committee of each institution. References Ferlay, J. et al. Global Cancer Observatory: Cancer Today (version 1.1). Lyon, France: International Agency for Research on Cancer 2024. Available from: https://gco.iarc.who.int/today , accessed [30 April 2025]. Hori, M. & Okuyama, A. Age-specific incidence rates of stomach cancer in the world. Jpn J. Clin. Oncol. 50 , 724–725. https://doi.org/10.1093/jjco/hyaa081 (2020). 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Perioperative outcomes and survival in elderly patients aged ≥ 75 years undergoing gastrectomy for gastric cancer: an 18-year retrospective analysis in a single Western centre. Langenbecks Arch. Surg. 406 , 1057–1069. https://doi.org/10.1007/s00423-021-02116-w (2021). Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterials.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":796919,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flows. ESD, endoscopic submucosal dissection; PS, propensity score.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7689469/v1/8d587f850476f4d35345623f.png"},{"id":94772637,"identity":"5fdbc7b9-50d3-4855-8caf-b9d2e590e95d","added_by":"auto","created_at":"2025-10-30 14:20:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1425158,"visible":true,"origin":"","legend":"\u003cp\u003eThe Kaplan-Meier curves for the long-term oncologic outcomes. Overall survival in the overall cohort (A) and propensity score-matched cohort (B). The incidence of gastric cancer recurrence in the overall cohort (C) and in the propensity score-matched cohort (D). ESD, endoscopic submucosal dissection.\u003c/p\u003e","description":"","filename":"Figure2Sinoverallcohort.png","url":"https://assets-eu.researchsquare.com/files/rs-7689469/v1/670634f63f0a9bf8a9539663.png"},{"id":104401940,"identity":"c9a9b48c-3159-42d6-be39-3f0ecc495532","added_by":"auto","created_at":"2026-03-11 12:13:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3319869,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7689469/v1/177fe2b0-d20e-41f4-84ca-620c6ed42173.pdf"},{"id":94772636,"identity":"c64e583e-2ce7-4fde-8a92-164cd184fe08","added_by":"auto","created_at":"2025-10-30 14:20:44","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":32738,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-7689469/v1/e8c09cb1cb7f24610c20363d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long-term outcomes after curative endoscopic submucosal dissection vs. gastrectomy in late elderly patients aged ≥75 years with early gastric cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGastric cancer is an age-related disease; it was detected in about two-thirds of patients aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e In Eastern Asian countries, including Korea, Japan, and China, the incidence of gastric cancer (GC) is the highest in the late elderly aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Because of multiple comorbidities that can affect outcomes, the decision for GC treatment is challenging in late elderly GC patients.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early GCs (EGCs) that meet curative resection criteria.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Additionally, ESD is a feasible treatment with acceptable long-term outcomes in EGC patients.\u003csup\u003e\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Given the high GC incidence, the number of elderly patients with EGC who could undergo ESD has increased.\u003c/p\u003e\u003cp\u003eA previous meta-analysis involving 18 retrospective studies reported that long-term overall survival (OS) after curative ESD of EGCs was comparable to that after gastrectomy.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Previous studies evaluating the long-term ESD outcomes compared to outcomes after gastrectomy have been conducted in younger GC patients (aged\u0026thinsp;\u0026lt;\u0026thinsp;70 years).\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Like the results in previous studies involving younger patients, comparable OS between ESD and gastrectomy has been reported in elderly EGC patients aged\u0026thinsp;\u0026ge;\u0026thinsp;70 years.\u003csup\u003e\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e However, previous studies included a small number of patients who underwent ESD (\u0026lt;\u0026thinsp;60 patients),\u003csup\u003e12, 13\u003c/sup\u003e short follow-up periods (median follow-up of \u0026lt;\u0026thinsp;2 years),\u003csup\u003e14\u003c/sup\u003e and higher proportions of patients with ESD with noncurative resection (\u0026gt;\u0026thinsp;50%).(15) The outcome comparisons between ESD and gastrectomy in late elderly EGC patients need to be investigated, including the patients with curative resection ESD criteria and long-term follow-up periods.\u003c/p\u003e\u003cp\u003eFor the EGCs that met the curative resection criteria for ESD, our study evaluated whether ESD was an acceptable treatment in late elderly EGC patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years compared with gastrectomy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients\u003c/h2\u003e\u003cp\u003eOur study was a multicenter retrospective study. EGC patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years who underwent ESD in 22 hospitals or gastrectomy in two hospitals from January 2011 to December 2020 were included. The patients had EGC lesions that met the curative ESD criteria on the final pathological evaluations after ESD or gastrectomy according to the GC treatment guideline (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Patients were excluded if their ESD results were noncurative, if they had a history of gastrectomy, or if they had incomplete information on follow-up status after treatment.\u003c/p\u003e\u003cp\u003eThis study was approved by the Institutional Review Board (IRB) of Pusan National University Hospital (IRB number 2309-031-131) and each of the other participating hospitals. Informed signed consents from the patients were waived by the IRB because of the minimal risk of this study. This study was conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eEndoscopic submucosal dissection procedure, gastrectomy, and pathological evaluation\u003c/h3\u003e\n\u003cp\u003eAn experienced endoscopist qualified by the Korean Society of Gastrointestinal Endoscopy had performed ESD, including lesion marking, precutting outside the marking, and submucosal dissection, with hemostasis for all non-bleeding visible vessels on the ESD ulcer bed. Surgical treatment consisted of radical gastrectomy and lymph node (LN) dissection, according to the GC treatment guideline.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Depending on the GC location, experienced surgeons performed total, pylorus-preserving, proximal, or distal gastrectomy.\u003c/p\u003e\u003cp\u003eThe resected EGC specimens were fixed and immersed in 10% neutral buffered formalin for preparing paraffin blocks. The section intervals of ESD and gastrectomy specimens were 2 mm and 4\u0026ndash;5 mm, respectively.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e The sliced specimens were embedded in paraffin, and hematoxylin/eosin-stained 5-\u0026micro;m sections of each paraffin block were evaluated by specialized gastrointestinal pathologists.\u003c/p\u003e\n\u003ch3\u003eFollow-up after early gastric cancer treatment\u003c/h3\u003e\n\u003cp\u003eFor patients curatively treated with ESD and gastrectomy, patients were followed up with endoscopy and abdominal computed tomography every 6 months for the first 2\u0026ndash;3 years and then annually until 5 years after treatment.\u003c/p\u003e\n\u003ch3\u003eStudy outcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was OS. Secondary outcomes were disease-specific survival (DSS) and GC recurrence. The event for OS was death from any cause whereas the event for DSS was death from GC or GC recurrence. Other outcomes included treatment-related adverse events (AEs) including death, and risk factors associated with overall mortality and GC recurrence. GC recurrence included local or distant recurrence, metachronous recurrence (GC occurring in the remnant stomach at one year or later after treatment). We collected data on deaths and GC recurrence until February 2025.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eAnalyses of descriptive data were conducted using the independent \u003cem\u003et\u003c/em\u003e test or Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e test for continuous variables and the chi-square or Fisher exact test for categorical variables. In this study, a propensity score (PS) matched analysis was performed to reduce selection bias between the treatment groups. A logistic regression model was used to estimate the PSs by including the following variables that could affect the outcomes of ESD and surgery: age, sex, comorbid illnesses (diabetes mellitus, hypertension, cardiovascular disease, and cerebrovascular disease), American Society of Anesthesiologists physical status (ASA) score, tumor characteristics (tumor size, depth, ulcer, histologic type), and curative ESD resection criteria (absolute vs. expanded criteria). A 4:1 nearest-neighbor matching was performed with a caliper of 0.2. Survival curves were obtained using the Kaplan\u0026ndash;Meier method. To compare the survival outcomes, we used the log-rank test for OS and Gray\u0026rsquo;s test for DSS and GC recurrence. The evaluation of risk factors for overall mortality and GC recurrence were performed using the Cox proportional hazard regression model and the Fine\u0026ndash;Gray regression model,\u003csup\u003e17\u003c/sup\u003e respectively. We used STATA 18.0 (StataCorp, College Station, TX, USA) and R version 4.4.3 for statistical analyses, and a \u003cem\u003eP\u003c/em\u003e-value of \u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003ePatient and GC characteristics\u003c/h2\u003e\u003cp\u003eThe detailed study flow is summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Totally 1,640 patients were excluded from the final cohort because of noncurative resection on the final pathological evaluation, previous gastrectomy history, and incomplete information on follow-up status. Finally, 4,120 patients who underwent ESD (ESD group) and 158 who underwent gastrectomy (surgery group) were included (overall cohort). After PS-matching (PSM), 632 patients in the ESD group and 158 in the surgery group were included in the PSM cohort).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eBaseline clinical and GC characteristics of the overall and PS-matched cohorts were described in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean patient age in the overall cohort was 78.7 years. The ESD group had a significantly older (mean age, 78.7 years vs. 78.0 years; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011) and a larger proportion of male patients (66.2% vs. 58.2%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.037) than the surgery group. The proportion of hypertension and chronic lung disease was lower in the ESD group, but patients with ASA score\u0026thinsp;\u0026ge;\u0026thinsp;3 were larger in the ESD group than in the surgery group (23.3% vs. 18.4%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Regarding tumor characteristics, the ESD group had a larger proportion of tumors with undifferentiated histologic type, lower 1/3 location, and absolute criteria, whereas the surgery group had a larger tumor size and a more proportion of tumors with ulcers. In the PSM cohort, the clinical and GC characteristics between the two groups were well balanced, with a standardized mean difference of \u0026lt;\u0026thinsp;0.2.\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\u003ePatient and tumor characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\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\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eOverall cohort\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eSMD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003ePropensity score-matched cohort\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eSMD\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eESD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSurgery\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eESD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSurgery\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(no\u0026thinsp;=\u0026thinsp;4,083)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(no\u0026thinsp;=\u0026thinsp;158)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e(no\u0026thinsp;=\u0026thinsp;632)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(no\u0026thinsp;=\u0026thinsp;158)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (year), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e78.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.219\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e78.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e78.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.056\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.175\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, no (%)\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\u003cp\u003e0.037\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.166\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.828\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.019\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\u003e1,379 (33.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66 (41.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e258 (40.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e66 (41.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\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\u003e2,704 (66.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e92 (58.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e374 (59.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e92 (58.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCo-morbid illnesses, no (%)\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\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,450 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e114 (72.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.259\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e399 (63.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e114 (72.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.034\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.194\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,036 (25.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39 (24.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.845\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e162 (25.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e39 (24.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.806\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.022\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiovascular disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e556 (13.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (8.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.085\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.151\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e74 (11.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e14 (8.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.309\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.094\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCerebrovascular disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e323 (7.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (7.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.664\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.036\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e67 (10.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e11 (7.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.170\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.129\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic liver disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67 (1.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.180\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.183\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.134\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.188\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic lung disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e236 (5.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (10.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.023\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.161\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e34 (5.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e16 (10.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.028\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.178\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic kidney disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e306 (7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (7.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.962\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e56 (8.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12 (7.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.612\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.046\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther malignancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e354 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.190\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.115\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e57 (9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e9 (5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.177\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.128\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASA PS score, no (%)\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\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.636\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.571\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e674 (16.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e92 (14.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (0.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,458 (60.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e128 (81.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e403 (63.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e128 (81.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3 or higher\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e951 (23.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29 (18.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e137 (21.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e29 (18.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eTumor histologic type, no (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.546\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDifferentiated type\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,001 (98.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e130 (82.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e560 (88.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e130 (82.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUndifferentiated type\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82 (2.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (17.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e72 (11.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e28 (17.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor size (mm), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.738\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e24.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e27.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.055\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.164\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor location, no (%)\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\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.329\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLower 1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,979 (73.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e96 (60.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e436 (69.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e96 (60.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.083\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.196\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMiddle 1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e788 (19.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53 (33.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e156 (24.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e53 (33.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUpper 1/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e316 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e40 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e9 (5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor depth, no (%)\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\u003cp\u003e0.803\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.304\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.096\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMucosa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3,844 (94.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e148 (94.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e576 (91.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e148 (93.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSM1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e239 (5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e56 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresence of ulcer, no (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e194 (4.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (14.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.337\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e111 (17.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e23 (14.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.368\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.082\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCurative resection criteria, no (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.156\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.962\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,713 (66.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (17.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e109 (17.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e27 (17.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExpanded\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,370 (33.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e131 (82.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e523 (82.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e131 (82.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e\u003cp\u003eAbbreviations: ESD, endoscopic submucosal dissection; SMD, standardized mean difference; SD, standard deviation; ASA PS, American Society of Anesthesiologist Physical Status; SM, submucosa.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eComparison of long-term outcomes\u003c/h3\u003e\n\u003cp\u003eA median follow-up was 6.6 years (interquartile range [IQR], 4.6\u0026ndash;8.9 years), and the 5-year OS rates were 84.8% in the ESD group and 82.9% in the surgery group. No differences in the OS were observed between the ESD and surgery groups in the overall cohort (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.396) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA) or in the PSM cohort (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.248) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Seven GC-related deaths were observed in the ESD group. Of the patients who died of GC, three received systemic chemotherapy for extra-gastric recurrence, and four (two extra-gastric recurrences and two metachronous recurrences) were observed without treatment for the recurrence. In the overall cohort, DSS rates were not different between the two treatment groups (5-year DSS rates, 99.8% vs. 100%, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.554). No GC-related deaths were observed in PSM cohort.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIn the overall cohort, GC recurrence occurred in 248 patients (6.1%, 248 of the 4,083 patients; 190 metachronous recurrences, 52 local recurrences, and 6 extra-gastric recurrences) in the ESD group and one patient (0.6%, 1 of the 158 patients; 1 extra-gastric recurrence) in the surgery group (Table S2). Most of the patients with local (88.5%) and metachronous recurrences (93.7%) were treated by endoscopic therapy or surgical treatment. The 5-year incidences of GC recurrence were 9.3% in the ESD group and 0.7% in the surgery group, and the ESD group had a significantly higher incidence of GC recurrence compared to the surgery group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). Similarly, in the PSM cohort, the ESD group had a greater GC recurrence than the surgery group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD).\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eRisk factors for the overall mortality and GC recurrence\u003c/h2\u003e\u003cp\u003eRisk factors for overall mortality and GC recurrence were evaluated in the PSM cohort.\u003c/p\u003e\u003cp\u003eIn the univariate analyses, significant risk factors for overall mortality were age of 80\u0026thinsp;~\u0026thinsp;84 years and \u0026ge;\u0026thinsp;85 years; male sex; chronic liver disease, chronic kidney disease, and other malignancies; and, a higher ASA score (2 and \u0026ge;\u0026thinsp;3) (Table S3). In the multivariate analysis, the overall mortality after ESD (adjusted hazard ratio [aHR], 0.77; 95% confidence interval [CI], 0.57\u0026ndash;1.04) was not different from that after surgery (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Age of 80\u0026thinsp;~\u0026thinsp;84 years (aHR, 1.98; 95% CI, 1.48\u0026ndash;2.63) and \u0026ge;\u0026thinsp;85 years (aHR, 3.82; 95% CI, 2.39\u0026ndash;6.10), male sex (aHR, 1.55; 95% CI, 1.18\u0026ndash;2.04), presence of other malignancy (aHR, 1.63; 95% CI, 1.07\u0026ndash;2.48), and ASA score 2 (aHR, 1.81; 95% CI, 1.07\u0026ndash;3.05) were the significant risk factors for overall mortality.\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\u003eRisk factors associated with overall mortality and gastric cancer recurrence in multivariate analyses*\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\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\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eOverall mortality\u0026dagger;\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u003cp\u003eGastric cancer recurrence\u0026Dagger;\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal no.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eaHR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eaHR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment\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\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e158\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eESD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e632\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.57\u0026ndash;1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.088\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e19.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.47-150.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge group\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\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e75\u0026thinsp;~\u0026thinsp;79 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e545\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e80\u0026thinsp;~\u0026thinsp;84 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e206\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.48\u0026ndash;2.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.53\u0026ndash;2.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.737\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e85 years ~\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.39\u0026ndash;6.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.89\u0026ndash;1.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.867\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\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\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=\"left\" colname=\"c2\"\u003e\u003cp\u003e324\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\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\u003e466\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.18\u0026ndash;2.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic liver disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.99\u0026ndash;4.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.054\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic kidney disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.75\u0026ndash;1.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.525\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther malignancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.07\u0026ndash;2.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.023\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASA score\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\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e531\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.07\u0026ndash;3.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3 or higher\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e166\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.81\u0026ndash;2.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.207\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e\u003cp\u003eAbbreviations: ESD, endoscopic submucosal dissection; aHR, adjusted hazard ratio; CI, confidence interval.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e\u003cp\u003e*The analyses were performed in the propensity score-matched cohort.\u003c/p\u003e\u003cp\u003e\u0026dagger;The Cox-proportional hazard regression model was used to evaluate risk factors for the overall mortality.\u003c/p\u003e\u003cp\u003e\u0026Dagger;The Fine-Gray regression model was used to evaluate risk factors for the gastric cancer recurrence.\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\u003eFor GC recurrence, ESD treatment and higher age groups of 80\u0026thinsp;~\u0026thinsp;84 years and \u0026ge;\u0026thinsp;85 years were significant risk factors in univariate analyses (Table S3). The risk of GC recurrence was significantly greater in the ESD group (aHR, 19.29; 95% CI, 2.47\u0026ndash;150.98) than in the surgery group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eHospital stays and treatment related AEs\u003c/h2\u003e\u003cp\u003eThe hospital duration for EGC treatment was shorter in the ESD group than that in the surgery group (median, 4 days vs. 10 days, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Total treatment-related AEs (7.6% vs. 12.0%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.044) and AEs requiring surgical treatment (0.1% vs. 1.3%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026) were less frequent in the ESD group than in the surgery group. In the surgery group, two patients (1.3%) died of treatment-related AEs (one died due to septic shock after developing anastomotic leakage and one due to septic shock caused by intestinal obstruction after postoperative adhesion). No deaths due to treatment-related AEs were observed in the ESD group.\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\u003eHospital stays and treatment related adverse events\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=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eTreatment group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eESD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSurgery\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(no\u0026thinsp;=\u0026thinsp;4,083)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(no\u0026thinsp;=\u0026thinsp;158)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospital stays (days), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (4\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (7\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" 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\u003eAdverse events\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\u003eTotal patients with adverse events, no (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e312 (7.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (12.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.044\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDetails of adverse events, no\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\u003eBleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e237\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\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\u003ePerforation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\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\u003ePneumonia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\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\u003eIleus or intestinal obstruction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\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\u003eAnastomotic leakage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\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\u003eIntraabdominal fluid collection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\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\u003eAnastomotic stricture\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\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\u003eWound dehiscence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\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\u003eLiver failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\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\u003ePulmonary thromboembolism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\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\u003eAdverse events requiring surgery, no (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (0.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (1.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.026\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeath due to adverse event, no (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (1.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eAbbreviations: ESD, endoscopic submucosal dissection; IQR, interquartile range.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis multi-center retrospective cohort study showed that the long-term OS after ESD was comparable to that after gastrectomy for EGC meeting the curative resection criteria of ESD in late elderly EGC patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years. Due to the higher rate of local or metachronous recurrence, the ESD group had a higher incidence of GC recurrence than the surgery group. However, most of the local and metachronous recurrences after ESD were treated endoscopically. In addition, the ESD group had shorter hospital stays and fewer treatment-related AEs than the surgery group.\u003c/p\u003e\u003cp\u003eGiven that \u0026gt;\u0026thinsp;70% of late elderly persons aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years had multiple comorbid illnesses,\u003csup\u003e18\u003c/sup\u003e minimally invasive treatments were preferred options to reduce treatment-related morbidity and mortality. In Korea and Japan, where the nationwide gastric cancer screening program was implemented, \u0026gt;50% of newly diagnosed GCs were in the localized stage,\u003csup\u003e19, 20\u003c/sup\u003e and the number of elderly GC patients indicated for ESD at the diagnosis has increased. In late elderly EGC patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years, ESD was technically feasible with the R0 resection rate of \u0026gt;\u0026thinsp;90% and acceptable treatment-related AEs.\u003csup\u003e\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Although previous studies have reported that the OS after ESD was comparable to that after gastrectomy in elderly EGC patients,\u003csup\u003e12\u0026ndash;14\u003c/sup\u003e in the previous studies, long-term survival outcomes were evaluated in patients with both curative and noncurative ESD. In elderly EGC patients with noncurative ESD, survival outcomes were affected by whether they underwent additional gastrectomy or not.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e For proper comparisons of survival outcomes, our study included only patients with EGCs that met the curative resection criteria of ESD to investigate the outcomes after ESD compared to those after gastrectomy.\u003c/p\u003e\u003cp\u003eIn our study, survival outcomes after ESD for late elderly patients with EGCs meeting the curative resection criteria were favorable, with a 5-year OS of 84.8% and DSS rate of 99.8%. In addition, the survival rates after ESD were comparable to those after gastrectomy in the overall and PSM cohorts, which was consistent with the findings of previous studies involving younger patients with EGC that compared outcomes between ESD and gastrectomy for GCs meeting curative resection criteria.\u003csup\u003e\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e In our study, although older age (80 to 84 years and \u0026gt;\u0026thinsp;85 years), presence of other malignancies, and ASA score 2 were risk factors for overall mortality in a multivariate analysis, the outcomes were not affected by treatment modality (ESD vs. gastrectomy) and curative resection criteria (absolute vs. expanded). These findings suggest that ESD is a primary treatment option over gastrectomy in late elderly EGC patients who have EGCs that meet the ESD curative resection criteria.\u003c/p\u003e\u003cp\u003eBecause of stomach preservation, metachronous recurrence was the main pattern of GC recurrence after curative ESD for EGCs, whereas extra-gastric recurrence was rare.\u003csup\u003e\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e The recurrence patterns were similar in elderly patients with EGC.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Due to metachronous recurrence after ESD, a higher GC recurrence rate was observed after ESD compared to gastrectomy.\u003csup\u003e\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Our study also reported a higher GC recurrence in the ESD group than in the surgery group, mainly because of local or metachronous recurrence after ESD. Like the previous studies involving younger or elderly patients with EGC, the majority of the local (71%) or metachronous (84%) cancers were successfully treated with endoscopic therapy. Thus, elderly patients with EGC who underwent ESD should be provided \u003cem\u003eHelicobacter pylori\u003c/em\u003e therapy to prevent metachronous recurrence and undergo long-term endoscopic surveillance to detect cancer recurrence at earlier stages like in younger EGC patients, according to guideline recommendations.\u003csup\u003e\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eTreatment-related AEs are another major concern in the treatment of EGCs in late elderly patients because many elderly patients have multiple comorbid illnesses. Due to poor nutritional status and pulmonary dysfunction, elderly patients with GC who underwent gastrectomy had significantly greater rates of anastomotic leakage and postoperative pneumonia than those in younger patients.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Previous studies comparing the outcomes of gastrectomy and ESD for EGCs also reported higher treatment-related AEs in patients who underwent gastrectomy, particularly late AEs occurring\u0026thinsp;\u0026gt;\u0026thinsp;30 days after treatment requiring endoscopic or surgical management.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e In studies involving elderly patients with EGC, the surgery group had higher AEs requiring intensive care unit admission and severe organ dysfunction (e.g., pneumonia and kidney injury) during the short-term postoperative period.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Rates of ESD related AEs were 8\u0026ndash;12%, and bleeding and perforation were major ESD-related AEs that could be treated with conservative or endoscopic therapy.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e In our study, patients who underwent ESD had less frequent total treatment-related AEs and AEs requiring surgery than those who underwent surgery. In addition, no treatment-related death was observed. The duration of the hospital stay was shorter in the ESD group than that in the surgery group. The findings provided robust evidence that ESD can be safely performed in elderly EGC patients, considering treatment-related AEs and mortality.\u003c/p\u003e\u003cp\u003eThis study evaluated the oncologic outcomes after ESD vs. gastrectomy in many late elderly EGC patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years (\u0026gt;\u0026thinsp;4,000 patients) during long-term follow-up. However, this study has several limitations. First, our study was a retrospective cohort study, and selection bias was unavoidable. To reduce bias, we evaluated outcomes in all patients and in the PSM cohort. In addition, a prospective randomized controlled trial may be unethical because ESD is the accepted treatment for EGCs meeting the guideline indication. Second, the risk factors associated with metachronous GC, including \u003cem\u003eH. pylori\u003c/em\u003e infection gastric atrophy, and intestinal metaplasia, were not evaluated in this study because it mainly focused on long-term oncologic outcomes. Third, the patient number in the surgery group was smaller than that in the ESD group, owing to the limited availability of surgical data.\u003c/p\u003e\u003cp\u003eIn conclusion, for late elderly GC patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years, long-term OS and DSS after ESD were comparable to those after gastrectomy for EGCs meeting the curative resection criteria of ESD. Even though a higher risk of GC recurrence was observed after ESD, mainly due to local or metachronous recurrence, most of these were manageable by endoscopic treatment. Considering the lower number of severe treatment-related AEs and higher prevalence of comorbid illnesses in late elderly patients with EGC, ESD might be a preferred primary treatment option over gastrectomy for EGCs meeting both absolute and expanded indications.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e: The authors declare no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding declaration\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eKorean College of \u003cem\u003eHelicobacter\u003c/em\u003e and Upper Gastrointestinal Research Foundation: grant number KCHUGR-202302501\u003c/p\u003e\n\u003cp\u003eNational Cancer Center: grant number 2310680 and 2311480\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeung Han Kim: data acquisition, drafting of article, critical revision for important intellectual content, and final approval of the manuscript\u003c/p\u003e\n\u003cp\u003eSeon-Young Park: data acquisition, drafting of article, critical revision for important intellectual content, and final approval of the manuscript\u003c/p\u003e\n\u003cp\u003eHyunsoo Chung:\u0026nbsp;guarantor of the article, data acquisition, drafting of article, critical revision for important intellectual content, and final approval of the manuscript\u003c/p\u003e\n\u003cp\u003eChung Hyun Tae: data acquisition, critical revision for important intellectual content, and final approval of the manuscript\u003c/p\u003e\n\u003cp\u003eHyeong Ho Jo: data acquisition, critical revision for important intellectual content, and final approval of the manuscript\u003c/p\u003e\n\u003cp\u003eJeong Hoon Lee: data acquisition, critical revision for important intellectual content, and final approval of the manuscript\u003c/p\u003e\n\u003cp\u003eAyoung Lee:\u0026nbsp;data acquisition, critical revision for important intellectual content, and final approval of the manuscript\u003c/p\u003e\n\u003cp\u003eJae Myung Park:\u0026nbsp;data acquisition, critical revision for important intellectual content, and final approval of the manuscript\u003c/p\u003e\n\u003cp\u003eHwoon-Yong Jung:\u0026nbsp;data acquisition, critical revision for important intellectual content, and final approval of the manuscript\u003c/p\u003e\n\u003cp\u003eYoung-Il Kim: guarantor of the article, conception and design of the study, data acquisition and interpretation, drafting of article, critical revision for important intellectual content, and final approval of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board (IRB) of Pusan National University Hospital (IRB number 2309-031-131) and each of the other participating hospitals. Informed signed consents from the patients were waived by the IRB because of the minimal risk of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA list of the Korean elderly ESD study group is provided in the supplementary material.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used in the current study are available from the corresponding author (YI Kim) on reasonable request after approval of the ethics committee of each institution. \u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFerlay, J. et al. Global Cancer Observatory: Cancer Today (version 1.1). Lyon, France: International Agency for Research on Cancer 2024. 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Surg.\u003c/em\u003e \u003cb\u003e406\u003c/b\u003e, 1057\u0026ndash;1069. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00423-021-02116-w\u003c/span\u003e\u003cspan address=\"10.1007/s00423-021-02116-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2021).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Elderly, Early gastric cancer, Endoscopic submucosal dissection, Gastrectomy","lastPublishedDoi":"10.21203/rs.3.rs-7689469/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7689469/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"This study compares outcomes of endoscopic submucosal dissection (ESD) with those of gastrectomy in late elderly patients aged ≥75 years with early gastric cancers (EGCs) that meet the curative resection criteria. We included 4,241 elderly EGC patients treated with either ESD (n=4,083) or gastrectomy (n=158) between 2010 and 2020. The primary outcome was overall survival (OS), and was investigated in the overall cohort and the 4-to-1 propensity score (PS)-matched cohort. During a median follow-up of 6.6 years, the 5-year OS rates were 84.8% and 82.9% in the ESD and surgery groups, respectively; and the OS did not differ between the two groups in the overall and PS-matched cohorts (all P\u003e 0.05 by the log-rank test). In the PS-matched cohort, the multivariate analyses showed that ESD was not a risk factor for overall mortality (adjusted hazard ratio, 0.77; 95% confidence interval, 0.57–1.04). The ESD group had fewer adverse events (AEs) (7.6% vs. 12.0%; P=0.044) than the surgery-group. In conclusion, long-term outcomes after ESD were comparable to those after gastrectomy in EGCs meeting the curative resection criteria with acceptable treatment-related AEs in late elderly EGC patients.","manuscriptTitle":"Long-term outcomes after curative endoscopic submucosal dissection vs. gastrectomy in late elderly patients aged ≥75 years with early gastric cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-30 14:20:39","doi":"10.21203/rs.3.rs-7689469/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"723ae431-f50f-4214-8f21-c4054458b45e","owner":[],"postedDate":"October 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56891436,"name":"Biological sciences/Cancer"},{"id":56891437,"name":"Health sciences/Gastroenterology"},{"id":56891438,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-03-04T12:27:35+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-30 14:20:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7689469","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7689469","identity":"rs-7689469","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}