Radiotherapy and Cancer-Specific Survival in Patients with Stage IV Rectal Cancer: A Large Population-Based Propensity Score–Matched Analysis

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While radiotherapy plays an established role in locally advanced rectal cancer, its clinical relevance in metastatic disease is less clearly defined. In particular, large population-based studies evaluating the relationship between radiotherapy and survival outcomes in metastatic rectal cancer are limited. Methods A retrospective population-based study was conducted using the Surveillance, Epidemiology, and End Results Program database. Patients diagnosed with stage IV rectosigmoid junction or rectal cancer were identified. Cancer-specific survival (CSS) was compared between patients who received radiotherapy and those who did not. Propensity score matching was performed to reduce baseline differences between the treatment groups. Survival outcomes were assessed using Kaplan–Meier analysis and Cox proportional hazards models. Subgroup analyses were also performed to explore the consistency of the findings across clinically relevant patient groups. Results Radiotherapy was associated with more favorable cancer-specific survival in the overall cohort. Patients treated with radiotherapy showed better CSS than those who did not receive radiotherapy. Multivariable Cox regression analysis also indicated that radiotherapy use was independently associated with cancer-specific survival. Similar trends were observed across most of the evaluated clinical subgroups. Conclusions In this population-based study, radiotherapy use was associated with favorable cancer-specific survival in patients with stage IV rectosigmoid junction or rectal cancer. Because registry-based analyses cannot establish causality, these findings should be interpreted with caution. Further prospective studies are needed to clarify the role of radiotherapy in the multidisciplinary management of metastatic rectal cancer. Rectal cancer Metastatic colorectal cancer Radiotherapy Cancer-specific survival Propensity score matching Population-based study Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide 1 , 2 . Although advances in systemic therapy have improved outcomes in metastatic disease, stage IV colorectal cancer continues to carry a poor prognosis, with a 5-year overall survival of approximately 14–20% for patients with unresectable disease 3 , 4 . In particular, the optimal multidisciplinary management strategy for patients with metastatic rectal cancer remains an area of ongoing debate, and current clinical practice guidelines emphasize that treatment should be individualized based on patient characteristics, tumor burden, and available therapeutic options 5 . In patients with stage IV rectal cancer, surgical resection of the primary tumor is sometimes performed to prevent or manage local complications such as obstruction, bleeding, or perforation. Several retrospective and population-based studies have suggested that primary tumor resection may be associated with improved survival in selected patients with metastatic colorectal cancer 6 – 9 . However, recent randomized controlled trials have failed to demonstrate a clear survival benefit of upfront primary tumor resection in asymptomatic patients with unresectable metastases, highlighting the ongoing controversy regarding the role of local treatment in metastatic disease 8 , 10 , 11 . In this context, the potential role of additional local therapies, including radiotherapy, remains uncertain. Radiotherapy plays several roles in rectal cancer management. It is commonly used to improve local control in locally advanced disease. Unlike colon cancer, rectal cancer is uniquely suited for pelvic radiotherapy because of the high risk of local recurrence and the established role of radiation in locally advanced disease. In patients with metastatic rectal cancer, radiotherapy may be delivered for local disease control, symptom palliation, or as part of multimodal treatment strategies 12 , 13 . However, whether local radiotherapy is associated with improved systemic survival outcomes in patients with metastatic rectal cancer remains unclear, particularly in large population-based cohorts 12 , 14 . Given the widespread use of radiotherapy in rectal cancer management, understanding its potential association with survival outcomes in metastatic disease is of clinical importance. Therefore, the present study aimed to evaluate the association between radiotherapy and cancer-specific survival in patients with stage IV rectal cancer using a population-based dataset. Using the Surveillance, Epidemiology, and End Results (SEER) database, we performed a propensity score-matched analysis to investigate survival outcomes in patients with stage IV rectal cancer who received radiotherapy compared with those who did not. METHODS Study population Data for this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (Incidence – SEER Research Data, 17 Registries, November 2024 submission), which covers approximately 28% of the United States population. Because the SEER database contains de-identified, publicly available data, institutional review board approval and informed consent were not required. A total of 358,123 patients diagnosed with colorectal cancer between 2000 and 2015 were initially identified. Among these, 100,619 patients with tumors located in the rectosigmoid junction or rectum were selected using the SEER site recode “Colon and Rectum” based on the International Classification of Diseases for Oncology, Third Edition (ICD-O-3). Tumors located in the rectosigmoid junction were included because these tumors are often managed clinically according to rectal cancer treatment principles, particularly with respect to the potential use of radiotherapy. Only malignant tumors were included, and eligible histologic types included adenocarcinoma and related subtypes (ICD-O-3 codes 8020, 8021, 8140, 8144, 8210, 8211, 8220, 8221, 8261, 8263, 8480, 8481, and 8490). Patients aged 20–90 years at diagnosis and those with only one primary tumor were included. Patients with missing stage information (n = 29,582) or stage 0 disease (n = 2,684) were excluded, leaving 68,353 eligible patients. Cases lacking radiotherapy information (n = 80) and those receiving intraoperative radiation (n = 35), radioactive implants (n = 43), or radioisotopes (n = 16) were further excluded, resulting in 68,179 patients. Among these patients, 15,119 patients with stage IV disease at diagnosis were included in the final study cohort. Statistical analysis Statistical analyses were performed to compare clinical and oncological variables between patients who received radiotherapy and those who did not. Categorical variables were compared using Pearson’s chi-squared test or Fisher’s exact test, as appropriate. Cancer-specific survival (CSS) was defined as the primary endpoint and calculated from the time of diagnosis to death attributed to colorectal cancer according to the SEER cause-specific death classification. Patients who were alive or died from other causes were censored at the time of last follow-up. Survival curves were estimated using the Kaplan–Meier method and compared using the log-rank test. To identify factors associated with cancer-specific survival, univariable and multivariable Cox proportional hazards regression analyses were performed. Variables included in the multivariable analysis were age group, sex, tumor location, tumor grade, T stage, N stage, chemotherapy, and radiotherapy. To reduce potential selection bias between treatment groups, propensity score matching (PSM) was performed. Propensity scores were calculated using logistic regression based on baseline variables including age, sex, tumor location, tumor grade, T stage, N stage, and chemotherapy. One-to-one nearest-neighbor matching without replacement was conducted. Balance between matched groups was assessed using standardized mean differences, and a standardized mean difference < 0.1 was considered to indicate adequate balance. After matching, Kaplan–Meier survival analysis and Cox proportional hazards models were used to evaluate cancer-specific survival between the radiotherapy and non-radiotherapy groups. Subgroup analyses were performed to evaluate the association between radiotherapy and cancer-specific survival across predefined subgroups including sex, age group, tumor location, tumor grade, T stage, N stage, and chemotherapy status. Hazard ratios with 95% confidence intervals were calculated and presented using forest plots. All statistical analyses were performed using GraphPad Prism version 10.6.0 (GraphPad Software, San Diego, CA, USA) and JMP Student Edition 18.2.1 (SAS Institute Inc., Cary, NC, USA). A two-sided p-value of < 0.05 was considered statistically significant. RESULTS Patient, Oncological, and Treatment Characteristics A total of 15,119 patients with stage IV rectosigmoid junction or rectal cancer were included in the study cohort. Among them, 4,949 patients (32.7%) received radiotherapy, whereas 10,170 patients (67.3%) did not. Baseline demographic and oncological characteristics stratified by radiotherapy status are summarized in Table 1 . Significant differences between the radiotherapy and non-radiotherapy groups were observed for several variables, including sex ( P = 0.0074 ), age group ( P < 0.0001 ), race (P = 0.0270), primary tumor location ( P < 0.0001 ), histology ( P = 0.0056 ), tumor grade ( P = 0.0001 ), T stage ( P < 0.0001 ), and N stage ( P < 0.0001 ). Table 1. Baseline demographic and tumor characteristics of patients with stage IV rectosigmoid junction or rectal cancer stratified by radiotherapy status RT ( −) n = 10,170 RT (+) n = 4,949 P value Sex Male Female 6,074 (59.7%) 4,096 (40.3%) 3,068 (62.0%) 1,881 (38.0%) 0.0074 Age group <50 50-64 65-74 ≥75 1,833 (18.0%) 4,021 (39.5%) 2,258 (22.3%) 2,058 (20.2%) 1,170 (23.7%) 2,104 (42.5%) 990 (20.0%) 685 (13.8%) <0.0001 Race and origin White Hispanic Asian or Pacific Islander Black American Indian/Alaska Native Unknown 6,782 (66.7%) 1,306 (12.9%) 932 (9.2%) 1,043 (10.2%) 93 (0.9%) 14 (0.1%) 3,252 (65.7%) 656 (13.3%) 444 (9.0%) 531 (10.7%) 65 (1.3%) 1 (0.0%) 0.0270 Primary tumor location Rectosigmoid Junction Rectum 4,246 (41.8%) 5,924 (58.2%) 782 (15.8%) 4,167 (84.2%) <0.0001 Histology tub pap muc sig por 9,040 (88.9%) 464 (4.6%) 501 (4.9%) 162 (1.6%) 3 (0.0%) 4,325 (87.4%) 235 (4.7%) 312 (6.3%) 73 (1.5%) 4 (0.1%) 0.0056 Grade Well diff. (Grade I) Moderately diff. (Grade II) Poorly diff. (Grade III) Undiff. (Grade IV) Unknown 436 (4.3%) 5,639 (55.5%) 1,744 (17.1%) 167 (1.6%) 2184 (21.5%) 238 (4.8%) 2,855 (57.7%) 872 (17.6%) 83 (1.7%) 901 (18.2%) 0.0001 T factor T1 T2 T3 T4 TX 1,245 (12.2%) 255 (2.5%) 3,530 (34.7%) 2,012 (19.8%) 3,128 (30.8%) 538 (10.9%) 190 (3.8%) 2,290 (46.3%) 1,007 (20.3%) 924 (18.7%) <0.0001 N factor N0 N1 N2 NX 3,283 (32.3%) 2,810 (27.6%) 2,217 (21.8%) 1,860 (18.3%) 1,593 (32.2%) 1,813 (36.6%) 958 (19.4%) 585 (11.8%) <0.0001 RT, Radiotherapy; tub, tubular adenocarcinoma; pap, papillary adenocarcinoma; muc, mucinous adenocarcinoma; sig, signet-ring cell carcinoma; por, poorly differentiated adenocarcinoma; Grade I, well differentiated; Grade II, moderately differentiated; Grade III, poorly differentiated; Grade IV, undifferentiated Patients who received radiotherapy were more likely to have tumors located in the rectum rather than the rectosigmoid junction, whereas patients who did not receive radiotherapy had a higher proportion of tumors arising from the rectosigmoid junction. Treatment characteristics according to radiotherapy status are summarized in Supplementary Table 1. Patients who received radiotherapy were more likely to undergo primary tumor resection compared with those who did not receive radiotherapy (45.7% vs. 41.6%, P < 0.0001 ). Similarly, the proportion of patients receiving chemotherapy was significantly higher in the radiotherapy group (89.8% vs. 63.3%, P < 0.0001 ). Regarding treatment sequencing, patients in the radiotherapy group underwent heterogeneous treatment patterns, including radiotherapy alone (54.3%), radiotherapy prior to surgery (30.3%), radiotherapy after surgery (13.8%), and radiotherapy both before and after surgery (1.6%). Survival Analysis Kaplan–Meier analysis demonstrated that patients who received radiotherapy had significantly improved cancer-specific survival compared with those who did not receive radiotherapy ( P < 0.0001 ; HR = 1.327) (Fig. 2 A). Among patients who underwent primary tumor resection, the addition of radiotherapy was also associated with improved cancer-specific survival compared with surgery alone ( P < 0.0001 ; HR = 1.440) (Fig. 2 B). Multivariable Cox Proportional Hazards Analysis Multivariable Cox proportional hazards regression analysis was performed to identify factors independently associated with cancer-specific survival (Table 2 ). Table 2. Multivariable Cox proportional hazards analysis for cancer-specific survival in stage IV rectosigmoid junction or rectal cancer patients who underwent primary tumor resection HR 95% CI P value Sex Male Female Reference 0.99 0.97-1.01 0.317 Age group <50 50-64 65-74 ≥75 Reference 0.89 1.04 1.35 0.86-0.91 1.01-1.08 1.30-1.40 <0.001 0.007 <0.001 Race and origin White Hispanic Asian or Pacific Islander Black Others Reference 0.92 0.93 1.14 1.03 0.88-0.97 0.88-0.99 1.08-1.20 0.91-1.18 0.003 0.017 <0.001 0.609 Primary tumor location Rectosigmoid Junction Rectum Reference 0.98 0.96-1.00 0.086 Histology tub pap/muc sig/por Reference 0.92 1.32 0.87-0.97 1.20-1.44 0.003 <0.001 Grade Grade I/II Grade III/ IV Unknown Reference 1.23 0.96 1.19-1.27 0.93-0.99 <0.0001 0.012 T factor T1/2 T3 T4 TX Reference 0.88 1.14 1.05 0.85-0.91 1.10-1.18 1.01-1.08 <0.0001 <0.0001 0.011 N factor N0 N1 N2 NX Reference 0.91 1.13 1.09 0.88-0.94 1.09-1.17 1.05-1.14 <0.0001 <0.0001 <0.0001 Surgery Yes No Reference 1.47 1.43-1.50 <0.0001 Chemotherapy Yes No Reference 1.50 1.47-1.54 <0.0001 Radiotherapy Yes No Reference 1.06 1.04-1.08 <0.0001 Advanced age was significantly associated with worse survival, particularly in patients aged ≥ 75 years (HR 1.35, 95% CI 1.30–1.40, P < 0.001 ). Higher tumor grade and advanced T and N stages were also independently associated with poorer cancer-specific survival. Patients who did not undergo primary tumor resection had significantly worse survival compared with those who underwent surgery (HR 1.47, 95% CI 1.43–1.50, P < 0.001 ). Similarly, the absence of chemotherapy was associated with markedly poorer survival (HR 1.50, 95% CI 1.47–1.54, P < 0.001 ). Importantly, patients who did not receive radiotherapy had worse cancer-specific survival compared with those who received radiotherapy (HR 1.06, 95% CI 1.04–1.08, P < 0.001 ). Propensity Score–Matched Analysis To reduce potential selection bias, propensity score matching was performed among patients who underwent primary tumor resection. Before matching, significant differences were observed between the radiotherapy and non-radiotherapy groups in several clinicopathologic variables, including age group, primary tumor location, histology, tumor grade, T stage, N stage, and chemotherapy use (Table 3 ). Table 3. Baseline demographic and tumor characteristics before and after propensity score matching in stage IV rectosigmoid junction or rectal cancer patients who underwent primary tumor resection Overall After PSM RT ( −) n = 4,226 RT (+) n = 2,261 P value RT ( −) n = 1,683 RT (+) n = 1,683 P value Sex Male Female 2,480 (58.7%) 1,746 (41.3%) 1,364 (60.3%) 897 (39.7%) 0.1991 1,040 (61.8%) 643 (38.2%) 1,034 (61.4%) 649 (38.6%) 0.8316 Age group <50 50-64 65-74 ≥75 871 (20.6%) 1,664 (39.4%) 936 (22.1%) 755 (17.9%) 658 (29.1%) 972 (43.0%) 438 (19.4%) 193 (8.5%) <0.0001 423 (25.1%) 765 (45.5%) 332 (19.7%) 165 (9.7%) 429 (25.5%) 753 (44.8%) 337 (20.0%) 164 (9.7%) 0.9811 Race and origin White Hispanic Asian or Pacific Islander Black Others 2,884 (68.2%) 496 (11.8%) 444 (10.5%) 371 (8.8%) 31 (0.7%) 1,544 (68.3%) 285 (12.6%) 205 (9.1%) 200 (8.8%) 27 (1.2%) 0.1172 1,169 (69.5%) 205 (12.2%) 157 (9.3%) 136 (8.1%) 16 (0.9%) 1,174 (69.7%) 197 (11.7%) 165 (9.8%) 134 (8.0%) 13 (0.8%) 0.9520 Primary tumor location Rectosigmoid Junction Rectum 2,419 (57.2%) 1,807 (42.8%) 427 (18.9%) 1,834 (81.1%) <0.0001 429 (25.5%) 1,254 (74.5%) 426 (25.3%) 1,257 (74.7%) 0.9054 Histology tub pap/muc sig/por 3.714 (87.9%) 452 (10.7%) 60 (1.4%) 1,893 (83.7%) 337 (14.9%) 31 (1.4%) <0.0001 1,462 (86.9%) 200 (11.9%) 21 (1.2%) 1,444 (85.8%) 213 (12.7%) 26 (1.5%) 0.5905 Grade Grade I/II Grade III/ IV Unknown 2,954 (69.9%) 1,023 (24.2%) 249 (5.9%) 1,545 (68.3%) 3,502 (22.2%) 214 (9.5%) <0.0001 1,183 (70.3%) 367 (21.8%) 133 (7.9%) 1,161 (69.0%) 377 (22.4%) 145 (8.6%) 0.6508 T factor T1/2 T3 T4 TX 314 (7.4%) 2,567 (60.7%) 1,140 (27.0%) 205 (4.9%) 223 (9.9%) 1,459 (64.5%) 473 (20.9%) 106 (4.7%) <0.0001 153 (9.1%) 1,071 (63.6%) 354 (21.0%) 105 (6.3%) 168 (10.0%) 1,054 (62.6%) 364 (21.6%) 97 (5.8%) 0.7307 N factor N0 N1 N2 NX 809 (19.1%) 1,357 (32.1%) 1,909 (45.2%) 151 (3.6%) 590 (26.1%) 882 (39.0%) 713 (31.5%) 76 (3.4%) <0.0001 366 (21.8%) 593 (35.2%) 663 (39.4%) 61 (3.6%) 384 (22.8%) 593 (35.2%) 644 (38.3%) 62 (3.7%) 0.8693 Chemotherapy Yes No 2,816 (66.6%) 1,410 (33.4%) 2,155 (95.3%) 106 (4.7%) <0.0001 1,578 (93.8%) 105 (6.2%) 1,577 (93.7%) 106 (6.3%) 0.9433 After 1:1 nearest-neighbor propensity score matching, 1,683 patients were included in each group. Baseline characteristics were well balanced between the radiotherapy and non-radiotherapy groups after matching, with no significant differences observed across the evaluated variables. Survival Analysis After Propensity Score Matching Kaplan–Meier analysis of the propensity score–matched cohort demonstrated that patients who received radiotherapy had significantly improved cancer-specific survival compared with those treated with surgery alone ( P < 0.0001 ; HR = 1.310) (Fig. 3 ). Subgroup Analysis Subgroup analyses were performed in the propensity score–matched cohort to evaluate the association between radiotherapy and cancer-specific survival across clinically relevant subgroups (Fig. 4 ). Radiotherapy was associated with improved cancer-specific survival across most subgroups, including sex, age group, tumor location, tumor grade, T stage, N stage, and receipt of chemotherapy. The survival benefit of radiotherapy was consistent in both male and female patients, as well as in patients aged < 65 and ≥ 65 years. Similarly, radiotherapy was associated with improved cancer-specific survival in patients with tumors located in both the rectosigmoid junction and rectum, and across different tumor grades and T and N stages. Notably, the association between radiotherapy and improved survival was observed primarily among patients who received chemotherapy, whereas the effect was not statistically significant among patients who did not receive chemotherapy. The sequence of surgery and radiotherapy according to chemotherapy status after propensity score matching is shown in Supplementary Table 2. Among patients who received both chemotherapy and radiotherapy, radiation was administered prior to surgery in 65.2% of cases and after surgery in 31.3% of cases. In contrast, among patients who did not receive chemotherapy, postoperative radiotherapy was more common (61.3%), whereas preoperative radiotherapy was administered in 35.9% of cases (P < 0.0001). DISCUSSION In this population-based analysis using the SEER database, we examined the relationship between radiotherapy and cancer-specific survival in patients with stage IV rectosigmoid junction or rectal cancer. Patients who received radiotherapy had more favorable cancer-specific survival than those who did not. This pattern remained evident after propensity score matching, suggesting that the observed survival difference was not solely explained by baseline differences between the treatment groups. Subgroup analyses also showed generally consistent findings across most clinically relevant patient categories. The role of local treatment in metastatic colorectal cancer remains controversial. Several retrospective and population-based studies have reported that treatment directed at the primary tumor may be associated with improved outcomes in selected patients with metastatic disease. In contrast, randomized trials evaluating upfront primary tumor resection in asymptomatic patients with unresectable metastases have not demonstrated a clear survival advantage. These conflicting findings illustrate the ongoing uncertainty regarding how local therapies should be integrated into the treatment strategy for metastatic colorectal cancer. Compared with surgery, radiotherapy has received relatively limited attention in this setting. In clinical practice, radiotherapy is frequently used to control local symptoms such as bleeding, obstruction, or pelvic pain, and it may also be incorporated into broader multimodal treatment strategies. Nevertheless, data examining its association with survival outcomes in metastatic rectal cancer remain limited and are largely based on retrospective analyses. The present study adds population-level evidence indicating that radiotherapy use is associated with more favorable cancer-specific survival in patients with stage IV rectosigmoid junction or rectal cancer. Several explanations may account for this observation. One possibility is that radiotherapy improves local tumor control, thereby reducing complications that could worsen a patient’s general condition. Bleeding, obstruction, and pelvic pain may negatively affect performance status and can interfere with the delivery of systemic therapy. Effective local control may therefore help maintain a patient’s ability to receive ongoing systemic treatment. Another explanation relates to the broader context of multidisciplinary care. Radiotherapy is often integrated with systemic therapy and surgical management in selected patients with metastatic rectal cancer. Improved local disease management may reduce tumor-related morbidity and contribute to more stable overall disease control, which in turn could influence long-term outcomes. In the present cohort, radiotherapy was administered both before and after surgery among patients receiving chemotherapy, suggesting that the observed association cannot be explained solely by neoadjuvant chemoradiotherapy. Experimental and clinical studies have also suggested that radiotherapy may trigger systemic immune responses, a phenomenon sometimes described as the abscopal effect. Although such mechanisms are biologically intriguing, registry-based datasets do not provide the level of clinical or biological detail needed to evaluate these processes directly. The present analysis therefore cannot determine whether systemic immune effects contributed to the survival differences observed here. Taken together, the findings of this study suggest that radiotherapy use is associated with more favorable cancer-specific survival in certain patients with stage IV rectal cancer. Because metastatic rectal cancer is highly heterogeneous, treatment decisions should continue to be individualized through multidisciplinary discussion. The associations observed in this analysis should therefore be interpreted cautiously and should not be viewed as evidence of a direct causal effect of radiotherapy. Several limitations should be considered when interpreting these results. First, the retrospective design of the study introduces the possibility of selection bias. Propensity score matching was performed to reduce baseline differences between treatment groups, but residual confounding cannot be completely excluded. Second, the SEER database does not contain detailed information on radiotherapy dose, treatment fields, or treatment intent. Consequently, it is not possible to determine whether radiotherapy was directed at the primary tumor, metastatic lesions, or both. In addition, important clinical information related to metastatic disease is not captured in the SEER database. Details regarding the pattern, burden, and timing of metastases, as well as treatments directed at metastatic sites, are unavailable. These factors may substantially influence treatment selection and prognosis, and their absence represents an important source of potential confounding. Information on patient performance status and specific systemic therapy regimens is also not available. Despite these limitations, the SEER database provides a large population-based cohort that allows the evaluation of treatment patterns and survival outcomes in metastatic rectal cancer. Analyses based on large real-world datasets can complement findings from clinical trials and may help generate hypotheses for future prospective studies. In summary, radiotherapy was associated with favorable cancer-specific survival in patients with stage IV rectosigmoid junction or rectal cancer in this population-based study. Because registry-based analyses cannot establish causality, further prospective investigations are needed to clarify the role of radiotherapy within the multidisciplinary management of metastatic rectal cancer. CONCLUSION Radiotherapy was associated with favorable cancer-specific survival in patients with stage IV rectosigmoid junction or rectal cancer in this population-based analysis. This association persisted after propensity score matching and across multiple clinical subgroups. Given the limitations inherent to registry-based studies, these findings should be interpreted as observational associations. Further prospective studies are warranted to clarify the potential role of radiotherapy in the multidisciplinary management of metastatic rectal cancer. Declarations Authors’ contributions Taguchi, Shimomura, and Ohdan conceived and designed the report. Taguchi analyzed and interpreted the data. Shimomura, Yano, Sadatomo, Matsubara, Ishikawa, Watanabe, Sato, Moriuchi, Shiozaki, Matsubara, Yamaguchi, Shinohara, Morita, and Ohdan coordinated and critically revised the report. All authors read and approved the final manuscript. Funding Information The authors received no specific funding for this work. Conflicts of Interest All authors declare no conflicts of interest. Ethics Statements This study used de-identified data from the Surveillance, Epidemiology, and End Results Program database. Because the SEER database contains publicly available, de-identified patient information, institutional review board approval and informed consent were not required. Availability of Data and Materials. The data used in this study are publicly available from the SEER database (https://seer.cancer.gov/) upon reasonable request and completion of the SEER data-use agreement. References Chen X, Tian R, Chen Z, Quan L, Bei S. Global burden of colorectal cancer from 1990 to 2021: a systematic analysis from the Global Burden of Disease Study 2021. Front Oncol. 2025;15:1676855. Morris VK, et al. Treatment of Metastatic Colorectal Cancer: ASCO Guideline. J Clin Oncol. 2023;41:678–700. Eng C, et al. Colorectal cancer Lancet. 2024;404:294–310. Biller LH, Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021;325:669. You YN, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer. Dis Colon Rectum. 2020;63:1191–222. Maroney S, et al. 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The effect of primary tumor radiotherapy in patients with Unresectable stage IV Rectal or Rectosigmoid Cancer: a propensity score matching analysis for survival. Radiat Oncol. 2020;15:126. Additional Declarations No competing interests reported. Supplementary Files 20260430supportinginformation.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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9575565","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":634032918,"identity":"efc501ff-32e9-4fb0-98eb-c52adbe0390d","order_by":0,"name":"Kazuhiro Taguchi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIie3QMWvCQBTA8QeBc3mm64WEfoaEgm7tV0kQ4uLmIijoZJZ0Vyj6Fdrl5oODuuQjZIgIN8el6OaLQ6fmaLZS7g8Hx8GPxzsAm+0PxuHhVNUziXRnEH+/o4EwZNGm6EjA768l3Mmv8vavMtruymCYZbo6Tp4hlM6xhqBsJT5z4+osNAZFMQwTMSLCnjigbiWPDMJoKxRyPmE8Ec7yXcKAdlFG4vffGjLWRJY0pfdlJD5DIquGxAMiigiap3jrNI02n0SwaMgBPIVTHht24Uqpql6oF97LtHcVc3AP2Ud9ztt/7IccOkkuu5B7l+7EZrPZ/m031YZRZUH003oAAAAASUVORK5CYII=","orcid":"","institution":"Hiroshima University","correspondingAuthor":true,"prefix":"","firstName":"Kazuhiro","middleName":"","lastName":"Taguchi","suffix":""},{"id":634032919,"identity":"da3c697f-fca6-482d-9db5-0720aa16a903","order_by":1,"name":"Manabu Shimomura","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Manabu","middleName":"","lastName":"Shimomura","suffix":""},{"id":634032921,"identity":"a803407c-5bbe-46bd-9ec1-7e6048600d11","order_by":2,"name":"Takuya Yano","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Takuya","middleName":"","lastName":"Yano","suffix":""},{"id":634032923,"identity":"14446d29-182b-4521-ac06-edd962192720","order_by":3,"name":"Ai Sadatomo","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Ai","middleName":"","lastName":"Sadatomo","suffix":""},{"id":634032925,"identity":"8b5f208a-26b6-4c5f-8687-432d8630cfd2","order_by":4,"name":"Keiso Matsubara","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Keiso","middleName":"","lastName":"Matsubara","suffix":""},{"id":634032928,"identity":"e4256aaf-704f-4d18-bebb-8df5ff70ed21","order_by":5,"name":"Sho Ishikawa","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Sho","middleName":"","lastName":"Ishikawa","suffix":""},{"id":634032929,"identity":"4c84c3b9-8fc3-4114-a840-c4a49f906e92","order_by":6,"name":"Atsuhiro Watanabe","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Atsuhiro","middleName":"","lastName":"Watanabe","suffix":""},{"id":634032930,"identity":"e64294dc-ffd7-417b-9977-f3f3c96d74d8","order_by":7,"name":"Saki Sato","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Saki","middleName":"","lastName":"Sato","suffix":""},{"id":634032933,"identity":"2856761c-b6a0-45dd-968f-90d44acf511f","order_by":8,"name":"Toshiyuki Moriuchi","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Toshiyuki","middleName":"","lastName":"Moriuchi","suffix":""},{"id":634032936,"identity":"620cf06e-7a2a-4ec4-9061-6a80a3b78598","order_by":9,"name":"Shohei Shiozaki","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Shohei","middleName":"","lastName":"Shiozaki","suffix":""},{"id":634032937,"identity":"1f8ba64f-0f03-40be-bebf-de3c23551019","order_by":10,"name":"Kazuki Matsubara","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Kazuki","middleName":"","lastName":"Matsubara","suffix":""},{"id":634032942,"identity":"25162344-578e-44a9-9aa1-42ddf917e1cb","order_by":11,"name":"Mizuki Yamaguchi","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Mizuki","middleName":"","lastName":"Yamaguchi","suffix":""},{"id":634032943,"identity":"627bdd27-a4aa-4d5e-b12a-0ed8606c7f7f","order_by":12,"name":"Makoto Shinohara","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Makoto","middleName":"","lastName":"Shinohara","suffix":""},{"id":634032946,"identity":"cca5de5b-4270-4b08-80ba-9fb0006a4210","order_by":13,"name":"Hayato Morita","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Hayato","middleName":"","lastName":"Morita","suffix":""},{"id":634032948,"identity":"bd8b37b6-b9ca-4e7d-aef4-3564c1263f65","order_by":14,"name":"Hideki Ohdan","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Hideki","middleName":"","lastName":"Ohdan","suffix":""}],"badges":[],"createdAt":"2026-04-30 10:10:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9575565/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9575565/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108841681,"identity":"4019ecdf-c3ee-4000-be25-efe6e9efae5e","added_by":"auto","created_at":"2026-05-09 01:11:13","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":399959,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow diagram of patient selection from the SEER database.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients diagnosed with colorectal cancer between 2000 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. After applying the inclusion and exclusion criteria, patients with stage IV rectosigmoid junction or rectal cancer were included in the final cohort.\u003c/p\u003e","description":"","filename":"11.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9575565/v1/ac4e494ebe5d1cd3c3238b8d.jpg"},{"id":108841682,"identity":"3f1dc237-aceb-47d1-8b30-e8aca77feaf8","added_by":"auto","created_at":"2026-05-09 01:11:13","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":259557,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier curves of cancer-specific survival according to radiotherapy in patients with stage IV rectosigmoid junction or rectal cancer.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Cancer-specific survival of all stage IV patients stratified by receipt of radiotherapy. (B) Cancer-specific survival of patients who underwent primary tumor resection stratified by radiotherapy status (surgery alone vs surgery with radiotherapy). Hazard ratios (HRs) and corresponding p values were estimated using Cox proportional hazards models.\u003c/p\u003e","description":"","filename":"12.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9575565/v1/29575a488f2fbf1b12b465a6.jpg"},{"id":108841685,"identity":"8bd54e31-67c3-4889-9c70-dfbe0e573aa1","added_by":"auto","created_at":"2026-05-09 01:11:13","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":140164,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier curves of cancer-specific survival after propensity score matching in patients with stage IV rectosigmoid junction or rectal cancer who underwent primary tumor resection.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients treated with surgery plus radiotherapy were compared with those treated with surgery alone after propensity score matching. Survival differences were evaluated using the log-rank test.\u003c/p\u003e","description":"","filename":"13.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9575565/v1/6e239c28333c880c71efa638.jpg"},{"id":108977127,"identity":"213d8982-5fd9-4c1b-86cb-1c70d710dadf","added_by":"auto","created_at":"2026-05-11 11:30:29","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":204330,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSubgroup analysis of cancer-specific survival after propensity score matching.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHazard ratios comparing surgery with radiotherapy versus surgery alone are shown for each subgroup. Radiotherapy was associated with improved cancer-specific survival across most subgroups. Error bars represent 95% confidence intervals.\u003c/p\u003e","description":"","filename":"14.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9575565/v1/f8e90406fb4398512dbdda59.jpg"},{"id":108979612,"identity":"c8a05101-ad5e-4118-95e0-a7e9b199ec2b","added_by":"auto","created_at":"2026-05-11 12:00:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1460266,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9575565/v1/032eb585-591d-4fe6-b383-f226dfd08184.pdf"},{"id":108841684,"identity":"e56653d9-aa4d-4233-92e5-c151cbe609d5","added_by":"auto","created_at":"2026-05-09 01:11:13","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":28160,"visible":true,"origin":"","legend":"","description":"","filename":"20260430supportinginformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-9575565/v1/3e87a57b7c62952194fb0d2c.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eRadiotherapy and Cancer-Specific Survival in Patients with Stage IV Rectal Cancer: A Large Population-Based Propensity Score–Matched Analysis \u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eColorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Although advances in systemic therapy have improved outcomes in metastatic disease, stage IV colorectal cancer continues to carry a poor prognosis, with a 5-year overall survival of approximately 14\u0026ndash;20% for patients with unresectable disease\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. In particular, the optimal multidisciplinary management strategy for patients with metastatic rectal cancer remains an area of ongoing debate, and current clinical practice guidelines emphasize that treatment should be individualized based on patient characteristics, tumor burden, and available therapeutic options\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e .\u003c/p\u003e \u003cp\u003eIn patients with stage IV rectal cancer, surgical resection of the primary tumor is sometimes performed to prevent or manage local complications such as obstruction, bleeding, or perforation. Several retrospective and population-based studies have suggested that primary tumor resection may be associated with improved survival in selected patients with metastatic colorectal cancer\u003csup\u003e\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. However, recent randomized controlled trials have failed to demonstrate a clear survival benefit of upfront primary tumor resection in asymptomatic patients with unresectable metastases, highlighting the ongoing controversy regarding the role of local treatment in metastatic disease\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. In this context, the potential role of additional local therapies, including radiotherapy, remains uncertain.\u003c/p\u003e \u003cp\u003eRadiotherapy plays several roles in rectal cancer management. It is commonly used to improve local control in locally advanced disease. Unlike colon cancer, rectal cancer is uniquely suited for pelvic radiotherapy because of the high risk of local recurrence and the established role of radiation in locally advanced disease. In patients with metastatic rectal cancer, radiotherapy may be delivered for local disease control, symptom palliation, or as part of multimodal treatment strategies\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. However, whether local radiotherapy is associated with improved systemic survival outcomes in patients with metastatic rectal cancer remains unclear, particularly in large population-based cohorts\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Given the widespread use of radiotherapy in rectal cancer management, understanding its potential association with survival outcomes in metastatic disease is of clinical importance.\u003c/p\u003e \u003cp\u003eTherefore, the present study aimed to evaluate the association between radiotherapy and cancer-specific survival in patients with stage IV rectal cancer using a population-based dataset. Using the Surveillance, Epidemiology, and End Results (SEER) database, we performed a propensity score-matched analysis to investigate survival outcomes in patients with stage IV rectal cancer who received radiotherapy compared with those who did not.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eData for this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (Incidence \u0026ndash; SEER Research Data, 17 Registries, November 2024 submission), which covers approximately 28% of the United States population. Because the SEER database contains de-identified, publicly available data, institutional review board approval and informed consent were not required.\u003c/p\u003e \u003cp\u003eA total of 358,123 patients diagnosed with colorectal cancer between 2000 and 2015 were initially identified. Among these, 100,619 patients with tumors located in the rectosigmoid junction or rectum were selected using the SEER site recode \u0026ldquo;Colon and Rectum\u0026rdquo; based on the International Classification of Diseases for Oncology, Third Edition (ICD-O-3). Tumors located in the rectosigmoid junction were included because these tumors are often managed clinically according to rectal cancer treatment principles, particularly with respect to the potential use of radiotherapy.\u003c/p\u003e \u003cp\u003eOnly malignant tumors were included, and eligible histologic types included adenocarcinoma and related subtypes (ICD-O-3 codes 8020, 8021, 8140, 8144, 8210, 8211, 8220, 8221, 8261, 8263, 8480, 8481, and 8490). Patients aged 20\u0026ndash;90 years at diagnosis and those with only one primary tumor were included.\u003c/p\u003e \u003cp\u003ePatients with missing stage information (n\u0026thinsp;=\u0026thinsp;29,582) or stage 0 disease (n\u0026thinsp;=\u0026thinsp;2,684) were excluded, leaving 68,353 eligible patients. Cases lacking radiotherapy information (n\u0026thinsp;=\u0026thinsp;80) and those receiving intraoperative radiation (n\u0026thinsp;=\u0026thinsp;35), radioactive implants (n\u0026thinsp;=\u0026thinsp;43), or radioisotopes (n\u0026thinsp;=\u0026thinsp;16) were further excluded, resulting in 68,179 patients.\u003c/p\u003e \u003cp\u003eAmong these patients, 15,119 patients with stage IV disease at diagnosis were included in the final study cohort.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed to compare clinical and oncological variables between patients who received radiotherapy and those who did not. Categorical variables were compared using Pearson\u0026rsquo;s chi-squared test or Fisher\u0026rsquo;s exact test, as appropriate.\u003c/p\u003e \u003cp\u003eCancer-specific survival (CSS) was defined as the primary endpoint and calculated from the time of diagnosis to death attributed to colorectal cancer according to the SEER cause-specific death classification. Patients who were alive or died from other causes were censored at the time of last follow-up. Survival curves were estimated using the Kaplan\u0026ndash;Meier method and compared using the log-rank test.\u003c/p\u003e \u003cp\u003eTo identify factors associated with cancer-specific survival, univariable and multivariable Cox proportional hazards regression analyses were performed. Variables included in the multivariable analysis were age group, sex, tumor location, tumor grade, T stage, N stage, chemotherapy, and radiotherapy.\u003c/p\u003e \u003cp\u003eTo reduce potential selection bias between treatment groups, propensity score matching (PSM) was performed. Propensity scores were calculated using logistic regression based on baseline variables including age, sex, tumor location, tumor grade, T stage, N stage, and chemotherapy. One-to-one nearest-neighbor matching without replacement was conducted. Balance between matched groups was assessed using standardized mean differences, and a standardized mean difference\u0026thinsp;\u0026lt;\u0026thinsp;0.1 was considered to indicate adequate balance.\u003c/p\u003e \u003cp\u003eAfter matching, Kaplan\u0026ndash;Meier survival analysis and Cox proportional hazards models were used to evaluate cancer-specific survival between the radiotherapy and non-radiotherapy groups.\u003c/p\u003e \u003cp\u003eSubgroup analyses were performed to evaluate the association between radiotherapy and cancer-specific survival across predefined subgroups including sex, age group, tumor location, tumor grade, T stage, N stage, and chemotherapy status. Hazard ratios with 95% confidence intervals were calculated and presented using forest plots.\u003c/p\u003e \u003cp\u003eAll statistical analyses were performed using GraphPad Prism version 10.6.0 (GraphPad Software, San Diego, CA, USA) and JMP Student Edition 18.2.1 (SAS Institute Inc., Cary, NC, USA). A two-sided p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient, Oncological, and Treatment Characteristics\u003c/h2\u003e\n \u003cp\u003eA total of 15,119 patients with stage IV rectosigmoid junction or rectal cancer were included in the study cohort. Among them, 4,949 patients (32.7%) received radiotherapy, whereas 10,170 patients (67.3%) did not.\u003c/p\u003e\n \u003cp\u003eBaseline demographic and oncological characteristics stratified by radiotherapy status are summarized in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Significant differences between the radiotherapy and non-radiotherapy groups were observed for several variables, including sex (\u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.0074\u003c/em\u003e), age group (\u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e), race (P\u0026thinsp;=\u0026thinsp;0.0270), primary tumor location (\u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e), histology (\u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.0056\u003c/em\u003e), tumor grade (\u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.0001\u003c/em\u003e), T stage (\u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e), and N stage (\u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eBaseline demographic and tumor characteristics of patients with stage IV rectosigmoid junction or rectal cancer stratified by radiotherapy status\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRT (\u003c/strong\u003e\u003cstrong\u003e\u0026minus;)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 10,170\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRT (+)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 4,949\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6,074 (59.7%)\u003c/p\u003e\n \u003cp\u003e4,096 (40.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3,068 (62.0%)\u003c/p\u003e\n \u003cp\u003e1,881 (38.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0074\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;50\u003c/p\u003e\n \u003cp\u003e50-64\u003c/p\u003e\n \u003cp\u003e65-74\u003c/p\u003e\n \u003cp\u003e\u0026ge;75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,833 (18.0%)\u003c/p\u003e\n \u003cp\u003e4,021 (39.5%)\u003c/p\u003e\n \u003cp\u003e2,258 (22.3%)\u003c/p\u003e\n \u003cp\u003e2,058 (20.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,170 (23.7%)\u003c/p\u003e\n \u003cp\u003e2,104 (42.5%)\u003c/p\u003e\n \u003cp\u003e990 (20.0%)\u003c/p\u003e\n \u003cp\u003e685 (13.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace and origin\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003cp\u003eHispanic\u003c/p\u003e\n \u003cp\u003eAsian or Pacific Islander\u003c/p\u003e\n \u003cp\u003eBlack\u003c/p\u003e\n \u003cp\u003eAmerican Indian/Alaska Native\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6,782 (66.7%)\u003c/p\u003e\n \u003cp\u003e1,306 (12.9%)\u003c/p\u003e\n \u003cp\u003e932 (9.2%)\u003c/p\u003e\n \u003cp\u003e1,043 (10.2%)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e93 (0.9%)\u003c/p\u003e\n \u003cp\u003e14 (0.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3,252 (65.7%)\u003c/p\u003e\n \u003cp\u003e656 (13.3%)\u003c/p\u003e\n \u003cp\u003e444 (9.0%)\u003c/p\u003e\n \u003cp\u003e531 (10.7%)\u003c/p\u003e\n \u003cp\u003e65 (1.3%)\u003c/p\u003e\n \u003cp\u003e1 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0270\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary tumor location\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eRectosigmoid Junction\u003c/p\u003e\n \u003cp\u003eRectum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4,246 (41.8%)\u003c/p\u003e\n \u003cp\u003e5,924 (58.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e782 (15.8%)\u003c/p\u003e\n \u003cp\u003e4,167 (84.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistology\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003etub\u003c/p\u003e\n \u003cp\u003epap\u003c/p\u003e\n \u003cp\u003emuc\u003c/p\u003e\n \u003cp\u003esig\u003c/p\u003e\n \u003cp\u003epor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9,040 (88.9%)\u003c/p\u003e\n \u003cp\u003e464 (4.6%)\u003c/p\u003e\n \u003cp\u003e501 (4.9%)\u003c/p\u003e\n \u003cp\u003e162 (1.6%)\u003c/p\u003e\n \u003cp\u003e3 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4,325 (87.4%)\u003c/p\u003e\n \u003cp\u003e235 (4.7%)\u003c/p\u003e\n \u003cp\u003e312 (6.3%)\u003c/p\u003e\n \u003cp\u003e73 (1.5%)\u003c/p\u003e\n \u003cp\u003e4 (0.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0056\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eWell diff. (Grade I)\u003c/p\u003e\n \u003cp\u003eModerately diff. (Grade II)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePoorly diff. (Grade III)\u003c/p\u003e\n \u003cp\u003eUndiff. (Grade IV)\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e436 (4.3%)\u003c/p\u003e\n \u003cp\u003e5,639 (55.5%)\u003c/p\u003e\n \u003cp\u003e1,744 (17.1%)\u003c/p\u003e\n \u003cp\u003e167 (1.6%)\u003c/p\u003e\n \u003cp\u003e2184 (21.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e238 (4.8%)\u003c/p\u003e\n \u003cp\u003e2,855 (57.7%)\u003c/p\u003e\n \u003cp\u003e872 (17.6%)\u003c/p\u003e\n \u003cp\u003e83 (1.7%)\u003c/p\u003e\n \u003cp\u003e901 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eT factor\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003cp\u003eTX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,245 (12.2%)\u003c/p\u003e\n \u003cp\u003e255 (2.5%)\u003c/p\u003e\n \u003cp\u003e3,530 (34.7%)\u003c/p\u003e\n \u003cp\u003e2,012 (19.8%)\u003c/p\u003e\n \u003cp\u003e3,128 (30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e538 (10.9%)\u003c/p\u003e\n \u003cp\u003e190 (3.8%)\u003c/p\u003e\n \u003cp\u003e2,290 (46.3%)\u003c/p\u003e\n \u003cp\u003e1,007 (20.3%)\u003c/p\u003e\n \u003cp\u003e924 (18.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN factor\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN0\u003c/p\u003e\n \u003cp\u003eN1\u003c/p\u003e\n \u003cp\u003eN2\u003c/p\u003e\n \u003cp\u003eNX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3,283 (32.3%)\u003c/p\u003e\n \u003cp\u003e2,810 (27.6%)\u003c/p\u003e\n \u003cp\u003e2,217 (21.8%)\u003c/p\u003e\n \u003cp\u003e1,860 (18.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,593 (32.2%)\u003c/p\u003e\n \u003cp\u003e1,813 (36.6%)\u003c/p\u003e\n \u003cp\u003e958 (19.4%)\u003c/p\u003e\n \u003cp\u003e585 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eRT, Radiotherapy; tub, tubular adenocarcinoma; pap, papillary adenocarcinoma; muc, mucinous adenocarcinoma; sig, signet-ring cell carcinoma; por, poorly differentiated adenocarcinoma; Grade I, well differentiated; Grade II, moderately differentiated; Grade III, poorly differentiated; Grade IV, undifferentiated\u003c/p\u003e\n \u003c/div\u003e\n \u003cp\u003ePatients who received radiotherapy were more likely to have tumors located in the rectum rather than the rectosigmoid junction, whereas patients who did not receive radiotherapy had a higher proportion of tumors arising from the rectosigmoid junction.\u003c/p\u003e\n \u003cp\u003eTreatment characteristics according to radiotherapy status are summarized in Supplementary Table 1. Patients who received radiotherapy were more likely to undergo primary tumor resection compared with those who did not receive radiotherapy (45.7% vs. 41.6%, \u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e). Similarly, the proportion of patients receiving chemotherapy was significantly higher in the radiotherapy group (89.8% vs. 63.3%, \u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e).\u003c/p\u003e\n \u003cp\u003eRegarding treatment sequencing, patients in the radiotherapy group underwent heterogeneous treatment patterns, including radiotherapy alone (54.3%), radiotherapy prior to surgery (30.3%), radiotherapy after surgery (13.8%), and radiotherapy both before and after surgery (1.6%).\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eSurvival Analysis\u003c/h3\u003e\n\u003cp\u003eKaplan\u0026ndash;Meier analysis demonstrated that patients who received radiotherapy had significantly improved cancer-specific survival compared with those who did not receive radiotherapy (\u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e; HR\u0026thinsp;=\u0026thinsp;1.327) (Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA).\u003c/p\u003e\n\u003cp\u003eAmong patients who underwent primary tumor resection, the addition of radiotherapy was also associated with improved cancer-specific survival compared with surgery alone (\u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e; HR\u0026thinsp;=\u0026thinsp;1.440) (Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB).\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eMultivariable Cox Proportional Hazards Analysis\u003c/h2\u003e\n \u003cp\u003eMultivariable Cox proportional hazards regression analysis was performed to identify factors independently associated with cancer-specific survival (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eMultivariable Cox proportional hazards analysis for cancer-specific survival in stage IV rectosigmoid junction or rectal cancer patients who underwent primary tumor resection\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.97-1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.317\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;50\u003c/p\u003e\n \u003cp\u003e50-64\u003c/p\u003e\n \u003cp\u003e65-74\u003c/p\u003e\n \u003cp\u003e\u0026ge;75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003cp\u003e1.04\u003c/p\u003e\n \u003cp\u003e1.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.86-0.91\u003c/p\u003e\n \u003cp\u003e1.01-1.08\u003c/p\u003e\n \u003cp\u003e1.30-1.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.007\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace and origin\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003cp\u003eHispanic\u003c/p\u003e\n \u003cp\u003eAsian or Pacific Islander\u003c/p\u003e\n \u003cp\u003eBlack\u003c/p\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003cp\u003e1.14\u003c/p\u003e\n \u003cp\u003e1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.88-0.97\u003c/p\u003e\n \u003cp\u003e0.88-0.99\u003c/p\u003e\n \u003cp\u003e1.08-1.20\u003c/p\u003e\n \u003cp\u003e0.91-1.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.003\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.017\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.609\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary tumor location\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eRectosigmoid Junction\u003c/p\u003e\n \u003cp\u003eRectum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.96-1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.086\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistology\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003etub\u003c/p\u003e\n \u003cp\u003epap/muc\u003c/p\u003e\n \u003cp\u003esig/por\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003cp\u003e1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.87-0.97\u003c/p\u003e\n \u003cp\u003e1.20-1.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.003\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eGrade I/II\u003c/p\u003e\n \u003cp\u003eGrade III/ IV\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003cp\u003e1.23\u003c/p\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.19-1.27\u003c/p\u003e\n \u003cp\u003e0.93-0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.012\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eT factor\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eT1/2\u003c/p\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003cp\u003eTX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003cp\u003e1.14\u003c/p\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.85-0.91\u003c/p\u003e\n \u003cp\u003e1.10-1.18\u003c/p\u003e\n \u003cp\u003e1.01-1.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.011\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN factor\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN0\u003c/p\u003e\n \u003cp\u003eN1\u003c/p\u003e\n \u003cp\u003eN2\u003c/p\u003e\n \u003cp\u003eNX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003cp\u003e1.13\u003c/p\u003e\n \u003cp\u003e1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.88-0.94\u003c/p\u003e\n \u003cp\u003e1.09-1.17\u003c/p\u003e\n \u003cp\u003e1.05-1.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003cp\u003e1.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.43-1.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eChemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003cp\u003e1.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.47-1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRadiotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003cp\u003e1.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.04-1.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eAdvanced age was significantly associated with worse survival, particularly in patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years (HR 1.35, 95% CI 1.30\u0026ndash;1.40, \u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e). Higher tumor grade and advanced T and N stages were also independently associated with poorer cancer-specific survival.\u003c/p\u003e\n \u003cp\u003ePatients who did not undergo primary tumor resection had significantly worse survival compared with those who underwent surgery (HR 1.47, 95% CI 1.43\u0026ndash;1.50, \u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e). Similarly, the absence of chemotherapy was associated with markedly poorer survival (HR 1.50, 95% CI 1.47\u0026ndash;1.54, \u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e).\u003c/p\u003e\n \u003cp\u003eImportantly, patients who did not receive radiotherapy had worse cancer-specific survival compared with those who received radiotherapy (HR 1.06, 95% CI 1.04\u0026ndash;1.08, \u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003ePropensity Score\u0026ndash;Matched Analysis\u003c/h3\u003e\n\u003cp\u003eTo reduce potential selection bias, propensity score matching was performed among patients who underwent primary tumor resection. Before matching, significant differences were observed between the radiotherapy and non-radiotherapy groups in several clinicopathologic variables, including age group, primary tumor location, histology, tumor grade, T stage, N stage, and chemotherapy use (Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eBaseline demographic and tumor characteristics before and after propensity score matching in stage IV rectosigmoid junction or rectal cancer patients who underwent primary tumor resection\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"648\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter PSM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRT (\u003c/strong\u003e\u003cstrong\u003e\u0026minus;)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 4,226\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRT (+)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 2,261\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRT (\u003c/strong\u003e\u003cstrong\u003e\u0026minus;)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 1,683\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRT (+)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 1,683\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2,480 (58.7%)\u003c/p\u003e\n \u003cp\u003e1,746 (41.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,364 (60.3%)\u003c/p\u003e\n \u003cp\u003e897 (39.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.1991\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,040 (61.8%)\u003c/p\u003e\n \u003cp\u003e643 (38.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,034 (61.4%)\u003c/p\u003e\n \u003cp\u003e649 (38.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.8316\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;50\u003c/p\u003e\n \u003cp\u003e50-64\u003c/p\u003e\n \u003cp\u003e65-74\u003c/p\u003e\n \u003cp\u003e\u0026ge;75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e871 (20.6%)\u003c/p\u003e\n \u003cp\u003e1,664 (39.4%)\u003c/p\u003e\n \u003cp\u003e936 (22.1%)\u003c/p\u003e\n \u003cp\u003e755 (17.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e658 (29.1%)\u003c/p\u003e\n \u003cp\u003e972 (43.0%)\u003c/p\u003e\n \u003cp\u003e438 (19.4%)\u003c/p\u003e\n \u003cp\u003e193 (8.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e423 (25.1%)\u003c/p\u003e\n \u003cp\u003e765 (45.5%)\u003c/p\u003e\n \u003cp\u003e332 (19.7%)\u003c/p\u003e\n \u003cp\u003e165 (9.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e429 (25.5%)\u003c/p\u003e\n \u003cp\u003e753 (44.8%)\u003c/p\u003e\n \u003cp\u003e337 (20.0%)\u003c/p\u003e\n \u003cp\u003e164 (9.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.9811\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace and origin\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003cp\u003eHispanic\u003c/p\u003e\n \u003cp\u003eAsian or Pacific Islander\u003c/p\u003e\n \u003cp\u003eBlack\u003c/p\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2,884 (68.2%)\u003c/p\u003e\n \u003cp\u003e496 (11.8%)\u003c/p\u003e\n \u003cp\u003e444 (10.5%)\u003c/p\u003e\n \u003cp\u003e371 (8.8%)\u003c/p\u003e\n \u003cp\u003e31 (0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,544 (68.3%)\u003c/p\u003e\n \u003cp\u003e285 (12.6%)\u003c/p\u003e\n \u003cp\u003e205 (9.1%)\u003c/p\u003e\n \u003cp\u003e200 (8.8%)\u003c/p\u003e\n \u003cp\u003e27 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.1172\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,169 (69.5%)\u003c/p\u003e\n \u003cp\u003e205 (12.2%)\u003c/p\u003e\n \u003cp\u003e157 (9.3%)\u003c/p\u003e\n \u003cp\u003e136 (8.1%)\u003c/p\u003e\n \u003cp\u003e16 (0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,174 (69.7%)\u003c/p\u003e\n \u003cp\u003e197 (11.7%)\u003c/p\u003e\n \u003cp\u003e165 (9.8%)\u003c/p\u003e\n \u003cp\u003e134 (8.0%)\u003c/p\u003e\n \u003cp\u003e13 (0.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.9520\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary tumor location\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eRectosigmoid Junction\u003c/p\u003e\n \u003cp\u003eRectum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2,419 (57.2%)\u003c/p\u003e\n \u003cp\u003e1,807 (42.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e427 (18.9%)\u003c/p\u003e\n \u003cp\u003e1,834 (81.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e429 (25.5%)\u003c/p\u003e\n \u003cp\u003e1,254 (74.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e426 (25.3%)\u003c/p\u003e\n \u003cp\u003e1,257 (74.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.9054\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistology\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003etub\u003c/p\u003e\n \u003cp\u003epap/muc\u003c/p\u003e\n \u003cp\u003esig/por\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.714 (87.9%)\u003c/p\u003e\n \u003cp\u003e452 (10.7%)\u003c/p\u003e\n \u003cp\u003e60 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,893 (83.7%)\u003c/p\u003e\n \u003cp\u003e337 (14.9%)\u003c/p\u003e\n \u003cp\u003e31 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,462 (86.9%)\u003c/p\u003e\n \u003cp\u003e200 (11.9%)\u003c/p\u003e\n \u003cp\u003e21 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,444 (85.8%)\u003c/p\u003e\n \u003cp\u003e213 (12.7%)\u003c/p\u003e\n \u003cp\u003e26 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.5905\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eGrade I/II\u003c/p\u003e\n \u003cp\u003eGrade III/ IV\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2,954 (69.9%)\u003c/p\u003e\n \u003cp\u003e1,023 (24.2%)\u003c/p\u003e\n \u003cp\u003e249 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,545 (68.3%)\u003c/p\u003e\n \u003cp\u003e3,502 (22.2%)\u003c/p\u003e\n \u003cp\u003e214 (9.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,183 (70.3%)\u003c/p\u003e\n \u003cp\u003e367 (21.8%)\u003c/p\u003e\n \u003cp\u003e133 (7.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,161 (69.0%)\u003c/p\u003e\n \u003cp\u003e377 (22.4%)\u003c/p\u003e\n \u003cp\u003e145 (8.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.6508\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT factor\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eT1/2\u003c/p\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003cp\u003eTX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e314 (7.4%)\u003c/p\u003e\n \u003cp\u003e2,567 (60.7%)\u003c/p\u003e\n \u003cp\u003e1,140 (27.0%)\u003c/p\u003e\n \u003cp\u003e205 (4.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e223 (9.9%)\u003c/p\u003e\n \u003cp\u003e1,459 (64.5%)\u003c/p\u003e\n \u003cp\u003e473 (20.9%)\u003c/p\u003e\n \u003cp\u003e106 (4.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e153 (9.1%)\u003c/p\u003e\n \u003cp\u003e1,071 (63.6%)\u003c/p\u003e\n \u003cp\u003e354 (21.0%)\u003c/p\u003e\n \u003cp\u003e105 (6.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e168 (10.0%)\u003c/p\u003e\n \u003cp\u003e1,054 (62.6%)\u003c/p\u003e\n \u003cp\u003e364 (21.6%)\u003c/p\u003e\n \u003cp\u003e97 (5.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.7307\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN factor\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN0\u003c/p\u003e\n \u003cp\u003eN1\u003c/p\u003e\n \u003cp\u003eN2\u003c/p\u003e\n \u003cp\u003eNX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e809 (19.1%)\u003c/p\u003e\n \u003cp\u003e1,357 (32.1%)\u003c/p\u003e\n \u003cp\u003e1,909 (45.2%)\u003c/p\u003e\n \u003cp\u003e151 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e590 (26.1%)\u003c/p\u003e\n \u003cp\u003e882 (39.0%)\u003c/p\u003e\n \u003cp\u003e713 (31.5%)\u003c/p\u003e\n \u003cp\u003e76 (3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e366 (21.8%)\u003c/p\u003e\n \u003cp\u003e593 (35.2%)\u003c/p\u003e\n \u003cp\u003e663 (39.4%)\u003c/p\u003e\n \u003cp\u003e61 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e384 (22.8%)\u003c/p\u003e\n \u003cp\u003e593 (35.2%)\u003c/p\u003e\n \u003cp\u003e644 (38.3%)\u003c/p\u003e\n \u003cp\u003e62 (3.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.8693\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2,816 (66.6%)\u003c/p\u003e\n \u003cp\u003e1,410 (33.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2,155 (95.3%)\u003c/p\u003e\n \u003cp\u003e106 (4.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,578 (93.8%)\u003c/p\u003e\n \u003cp\u003e105 (6.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,577 (93.7%)\u003c/p\u003e\n \u003cp\u003e106 (6.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.9433\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAfter 1:1 nearest-neighbor propensity score matching, 1,683 patients were included in each group. Baseline characteristics were well balanced between the radiotherapy and non-radiotherapy groups after matching, with no significant differences observed across the evaluated variables.\u003c/p\u003e\n\u003ch3\u003eSurvival Analysis After Propensity Score Matching\u003c/h3\u003e\n\u003cp\u003eKaplan\u0026ndash;Meier analysis of the propensity score\u0026ndash;matched cohort demonstrated that patients who received radiotherapy had significantly improved cancer-specific survival compared with those treated with surgery alone (\u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e; HR\u0026thinsp;=\u0026thinsp;1.310) (Fig. \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eSubgroup Analysis\u003c/h2\u003e\n \u003cp\u003eSubgroup analyses were performed in the propensity score\u0026ndash;matched cohort to evaluate the association between radiotherapy and cancer-specific survival across clinically relevant subgroups (Fig. \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eRadiotherapy was associated with improved cancer-specific survival across most subgroups, including sex, age group, tumor location, tumor grade, T stage, N stage, and receipt of chemotherapy. The survival benefit of radiotherapy was consistent in both male and female patients, as well as in patients aged\u0026thinsp;\u0026lt;\u0026thinsp;65 and \u0026ge;\u0026thinsp;65 years.\u003c/p\u003e\n \u003cp\u003eSimilarly, radiotherapy was associated with improved cancer-specific survival in patients with tumors located in both the rectosigmoid junction and rectum, and across different tumor grades and T and N stages.\u003c/p\u003e\n \u003cp\u003eNotably, the association between radiotherapy and improved survival was observed primarily among patients who received chemotherapy, whereas the effect was not statistically significant among patients who did not receive chemotherapy.\u003c/p\u003e\n \u003cp\u003eThe sequence of surgery and radiotherapy according to chemotherapy status after propensity score matching is shown in Supplementary Table\u0026nbsp;2. Among patients who received both chemotherapy and radiotherapy, radiation was administered prior to surgery in 65.2% of cases and after surgery in 31.3% of cases. In contrast, among patients who did not receive chemotherapy, postoperative radiotherapy was more common (61.3%), whereas preoperative radiotherapy was administered in 35.9% of cases (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this population-based analysis using the SEER database, we examined the relationship between radiotherapy and cancer-specific survival in patients with stage IV rectosigmoid junction or rectal cancer. Patients who received radiotherapy had more favorable cancer-specific survival than those who did not. This pattern remained evident after propensity score matching, suggesting that the observed survival difference was not solely explained by baseline differences between the treatment groups. Subgroup analyses also showed generally consistent findings across most clinically relevant patient categories.\u003c/p\u003e \u003cp\u003eThe role of local treatment in metastatic colorectal cancer remains controversial. Several retrospective and population-based studies have reported that treatment directed at the primary tumor may be associated with improved outcomes in selected patients with metastatic disease. In contrast, randomized trials evaluating upfront primary tumor resection in asymptomatic patients with unresectable metastases have not demonstrated a clear survival advantage. These conflicting findings illustrate the ongoing uncertainty regarding how local therapies should be integrated into the treatment strategy for metastatic colorectal cancer.\u003c/p\u003e \u003cp\u003eCompared with surgery, radiotherapy has received relatively limited attention in this setting. In clinical practice, radiotherapy is frequently used to control local symptoms such as bleeding, obstruction, or pelvic pain, and it may also be incorporated into broader multimodal treatment strategies. Nevertheless, data examining its association with survival outcomes in metastatic rectal cancer remain limited and are largely based on retrospective analyses. The present study adds population-level evidence indicating that radiotherapy use is associated with more favorable cancer-specific survival in patients with stage IV rectosigmoid junction or rectal cancer.\u003c/p\u003e \u003cp\u003eSeveral explanations may account for this observation. One possibility is that radiotherapy improves local tumor control, thereby reducing complications that could worsen a patient\u0026rsquo;s general condition. Bleeding, obstruction, and pelvic pain may negatively affect performance status and can interfere with the delivery of systemic therapy. Effective local control may therefore help maintain a patient\u0026rsquo;s ability to receive ongoing systemic treatment.\u003c/p\u003e \u003cp\u003eAnother explanation relates to the broader context of multidisciplinary care. Radiotherapy is often integrated with systemic therapy and surgical management in selected patients with metastatic rectal cancer. Improved local disease management may reduce tumor-related morbidity and contribute to more stable overall disease control, which in turn could influence long-term outcomes. In the present cohort, radiotherapy was administered both before and after surgery among patients receiving chemotherapy, suggesting that the observed association cannot be explained solely by neoadjuvant chemoradiotherapy.\u003c/p\u003e \u003cp\u003eExperimental and clinical studies have also suggested that radiotherapy may trigger systemic immune responses, a phenomenon sometimes described as the abscopal effect. Although such mechanisms are biologically intriguing, registry-based datasets do not provide the level of clinical or biological detail needed to evaluate these processes directly. The present analysis therefore cannot determine whether systemic immune effects contributed to the survival differences observed here.\u003c/p\u003e \u003cp\u003eTaken together, the findings of this study suggest that radiotherapy use is associated with more favorable cancer-specific survival in certain patients with stage IV rectal cancer. Because metastatic rectal cancer is highly heterogeneous, treatment decisions should continue to be individualized through multidisciplinary discussion. The associations observed in this analysis should therefore be interpreted cautiously and should not be viewed as evidence of a direct causal effect of radiotherapy.\u003c/p\u003e \u003cp\u003eSeveral limitations should be considered when interpreting these results. First, the retrospective design of the study introduces the possibility of selection bias. Propensity score matching was performed to reduce baseline differences between treatment groups, but residual confounding cannot be completely excluded. Second, the SEER database does not contain detailed information on radiotherapy dose, treatment fields, or treatment intent. Consequently, it is not possible to determine whether radiotherapy was directed at the primary tumor, metastatic lesions, or both.\u003c/p\u003e \u003cp\u003eIn addition, important clinical information related to metastatic disease is not captured in the SEER database. Details regarding the pattern, burden, and timing of metastases, as well as treatments directed at metastatic sites, are unavailable. These factors may substantially influence treatment selection and prognosis, and their absence represents an important source of potential confounding. Information on patient performance status and specific systemic therapy regimens is also not available.\u003c/p\u003e \u003cp\u003eDespite these limitations, the SEER database provides a large population-based cohort that allows the evaluation of treatment patterns and survival outcomes in metastatic rectal cancer. Analyses based on large real-world datasets can complement findings from clinical trials and may help generate hypotheses for future prospective studies.\u003c/p\u003e \u003cp\u003eIn summary, radiotherapy was associated with favorable cancer-specific survival in patients with stage IV rectosigmoid junction or rectal cancer in this population-based study. Because registry-based analyses cannot establish causality, further prospective investigations are needed to clarify the role of radiotherapy within the multidisciplinary management of metastatic rectal cancer.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eRadiotherapy was associated with favorable cancer-specific survival in patients with stage IV rectosigmoid junction or rectal cancer in this population-based analysis. This association persisted after propensity score matching and across multiple clinical subgroups. Given the limitations inherent to registry-based studies, these findings should be interpreted as observational associations. Further prospective studies are warranted to clarify the potential role of radiotherapy in the multidisciplinary management of metastatic rectal cancer.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTaguchi, Shimomura, and Ohdan conceived and designed the report. Taguchi analyzed and interpreted the data. Shimomura, Yano, Sadatomo, Matsubara, Ishikawa, Watanabe, Sato, Moriuchi, Shiozaki, Matsubara, Yamaguchi, Shinohara, Morita, and Ohdan coordinated and critically revised the report. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no specific funding for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study used de-identified data from the Surveillance, Epidemiology, and End Results Program database. Because the SEER database contains publicly available, de-identified patient information, institutional review board approval and informed consent were not required. Availability of Data and Materials. The data used in this study are publicly available from the SEER database (https://seer.cancer.gov/) upon reasonable request and completion of the SEER data-use agreement.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChen X, Tian R, Chen Z, Quan L, Bei S. Global burden of colorectal cancer from 1990 to 2021: a systematic analysis from the Global Burden of Disease Study 2021. Front Oncol. 2025;15:1676855.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorris VK, et al. Treatment of Metastatic Colorectal Cancer: ASCO Guideline. J Clin Oncol. 2023;41:678\u0026ndash;700.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEng C, et al. Colorectal cancer Lancet. 2024;404:294\u0026ndash;310.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBiller LH, Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021;325:669.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYou YN, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer. Dis Colon Rectum. 2020;63:1191\u0026ndash;222.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaroney S, et al. Benefit of Surgical Resection of the Primary Tumor in Patients Undergoing Chemotherapy for Stage IV Colorectal Cancer with Unresected Metastasis. J Gastrointest Surg. 2018;22:460\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNitsche U, et al. Meta-analysis of outcomes following resection of the primary tumour in patients presenting with metastatic colorectal cancer. J Br Surg. 2018;105:784\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTarantino I, et al. Prognostic Relevance of Palliative Primary Tumor Removal in 37,793 Metastatic Colorectal Cancer Patients: A Population-Based, Propensity Score-Adjusted Trend Analysis. Ann Surg. 2015;262:112\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Rooijen KL, et al. Prognostic value of primary tumour resection in synchronous metastatic colorectal cancer: Individual patient data analysis of first-line randomised trials from the ARCAD database. Eur J Cancer. 2018;91:99\u0026ndash;106.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanemitsu Y, et al. Primary Tumor Resection Plus Chemotherapy Versus Chemotherapy Alone for Colorectal Cancer Patients With Asymptomatic, Synchronous Unresectable Metastases (JCOG1007; iPACS): A Randomized Clinical Trial. J Clin Oncol. 2021;39:1098\u0026ndash;107.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan der Kruijssen DEW, et al. Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group. Ann Oncol. 2024;35:769\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYin T-C, et al. Efficacy of concurrent radiotherapy in patients with locally advanced rectal cancer and synchronous metastasis receiving systemic therapy. Front Oncol. 2023;13:1099168.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKok END, et al. Multicentre study of short-course radiotherapy, systemic therapy and resection/ablation for stage IV rectal cancer. J Br Surg. 2020;107:537\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang G, et al. The effect of primary tumor radiotherapy in patients with Unresectable stage IV Rectal or Rectosigmoid Cancer: a propensity score matching analysis for survival. Radiat Oncol. 2020;15:126.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Rectal cancer, Metastatic colorectal cancer, Radiotherapy, Cancer-specific survival, Propensity score matching, Population-based study","lastPublishedDoi":"10.21203/rs.3.rs-9575565/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9575565/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe optimal multidisciplinary management of stage IV rectal cancer remains controversial. While radiotherapy plays an established role in locally advanced rectal cancer, its clinical relevance in metastatic disease is less clearly defined. In particular, large population-based studies evaluating the relationship between radiotherapy and survival outcomes in metastatic rectal cancer are limited.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective population-based study was conducted using the Surveillance, Epidemiology, and End Results Program database. Patients diagnosed with stage IV rectosigmoid junction or rectal cancer were identified. Cancer-specific survival (CSS) was compared between patients who received radiotherapy and those who did not. Propensity score matching was performed to reduce baseline differences between the treatment groups. Survival outcomes were assessed using Kaplan\u0026ndash;Meier analysis and Cox proportional hazards models. Subgroup analyses were also performed to explore the consistency of the findings across clinically relevant patient groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eRadiotherapy was associated with more favorable cancer-specific survival in the overall cohort. Patients treated with radiotherapy showed better CSS than those who did not receive radiotherapy. Multivariable Cox regression analysis also indicated that radiotherapy use was independently associated with cancer-specific survival. Similar trends were observed across most of the evaluated clinical subgroups.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn this population-based study, radiotherapy use was associated with favorable cancer-specific survival in patients with stage IV rectosigmoid junction or rectal cancer. Because registry-based analyses cannot establish causality, these findings should be interpreted with caution. Further prospective studies are needed to clarify the role of radiotherapy in the multidisciplinary management of metastatic rectal cancer.\u003c/p\u003e","manuscriptTitle":"Radiotherapy and Cancer-Specific Survival in Patients with Stage IV Rectal Cancer: A Large Population-Based Propensity Score–Matched Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-09 01:11:04","doi":"10.21203/rs.3.rs-9575565/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":"40a05f27-c5a7-489c-8dbe-b4f5852e8b48","owner":[],"postedDate":"May 9th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-07T22:17:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-04T09:45:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-05-04T09:44:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Radiation Oncology","date":"2026-04-30T09:58:23+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-09T01:11:06+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-09 01:11:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9575565","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9575565","identity":"rs-9575565","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}