Evaluating the Benefits of Tegafur-Uracil Adjuvant Therapy in Low-Risk Stage IIa Colon Cancer: Insights from a Decade-Long Study

Evaluating the Benefits of Tegafur-Uracil Adjuvant Therapy in Low-Risk Stage IIa Colon Cancer: Insights from a Decade-Long Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluating the Benefits of Tegafur-Uracil Adjuvant Therapy in Low-Risk Stage IIa Colon Cancer: Insights from a Decade-Long Study Chang-Lin Lin, Feng-Fan Chiang, Bo-Zh Lin, Ming-Cheng Chen, Chun-Yu Lin, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5816207/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Surgical resection is the gold standard for treating non-metastatic colorectal cancer. The five-year overall survival (OS) for Stage IIIa patients is longer than that for Stage IIa patients, highlighting the importance of adjuvant therapy (ACT) for Stage IIa. This study aims to evaluate the treatment outcomes and prognostic factors for Stage IIa colon cancer at our hospital over the past decade. Materials and Methods This retrospective study was conducted at a medical center and included patients treated between January 1, 2010, and December 31, 2019. We included only patients who underwent surgery and had pathological Stage IIa or IIIa colon cancer. Collected data included patient characteristics, oncological outcomes, receipt of adjuvant therapy, and adverse effects associated with adjuvant therapy. Result We observed a higher five-year OS for Stage IIIa than Stage IIa patients, but the difference was not statistically significant. Patients who were administered tegafur-uracil had longer five-year progression-free survival and five-year overall survival compared to the No ACT group (p < 0.005). The receiver operating characteristic curve identified the optimal cut-off point for tegafur-uracil (UFT) duration as ≤ 1.74 years, with the area under the curve being statistically significant ( p = 0.05). Conclusion ACT is recommended even for low-risk Stage IIa patients postoperatively. The adverse effects of UFT were generally acceptable, with Grade 3 or higher adverse effects being rare. If UFT is used as an ACT regimen for stage IIa colon cancer, a duration of more than one year is suggested. Tegafur Adjuvant chemotherapy Stage IIa colon cancer Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Colorectal cancer (CRC) has consistently ranked among the top two cancers in terms of incidence in Taiwan and was the third leading cause of death in 2023. (1, 2) Current treatment for CRC is primarily guided by the American Joint Committee on Cancer (AJCC) staging system, with curative surgery remaining the gold standard for non-metastatic CRC.(3) Patients with Stage I CRC typically require no adjuvant chemotherapy (ACT) and are only advised to undergo regular post-surgery follow-up. For Stage III patients, evidence from three landmark trials—MOSAIC, NSABP C-07, and NO16968/XELOXA(4–6)—supports the recommendation of doublet ACT to improve oncological outcomes following surgery. However, the benefit of ACT for Stage II patients has been a topic of debate, with varying opinions on whether it improves long-term outcomes. According to the AJCC staging system, tumors classified as T3 or higher without regional lymph node metastasis are considered Stage II. Regardless of T stage, tumors with regional lymph node metastasis but without distant metastasis are categorized as Stage III. Both Stage II and III are further subdivided into a, b, and c groups for more precise classification. Since the AJCC 6th edition, T3N0 has been specifically classified as Stage IIa,(7) while T1-2N1a and -N1c are categorized as Stage IIIa. In the AJCC 7th edition, T1N2a was newly added to Stage IIIa.(8) The distinction between Stage IIIa and Stage IIa is noteworthy because some real-world data indicate that the five-year overall survival (OS) for Stage IIIa is longer than that for Stage IIa.(9) A 2012 study published in the International Journal of Colorectal Disease reported a five-year OS rate of 85.4% for Stage IIIa, compared to 79.7% for Stage IIa.(10) These findings suggest that Stage IIa patients might require more aggressive postoperative treatment. According to the National Comprehensive Cancer Network (NCCN) guidelines, ACT options for Stage II colon cancer include 5-FU, oxaliplatin, and capecitabine.(11) However, in Taiwan, oxaliplatin and capecitabine are not covered by national health insurance (NHI) for Stage II colon cancer, leaving oral tegafur-uracil (UFT) as the primary ACT option.(12) NHI coverage for UFT extends up to two years. Currently, the guidelines do not clearly state whether ACT offers a survival benefit for Stage IIa colon cancer. This article presents a retrospective analysis of a decade’s worth of data from a single hospital, investigating whether the use of UFT for ACT improves the long-term outcomes for Stage IIa colon cancer patients. Methods Patients Data for this retrospective study were collected from the Taichung Veterans General Hospital Cancer Registry for all newly diagnosed CRC patients between 2010 and 2019. We included only patients who underwent curative surgery and were diagnosed with pathological stage II colon cancer. Rectal cancer was excluded because it often involves neoadjuvant therapy. Patients who died from surgical complications or had synchronous distant metastases were excluded. We defined "synchronous distant metastases" as metastases detected within six months of surgery. Additionally, patients who received oral capecitabine or intravenous 5-FU with or without oxaliplatin were excluded. After excluding patients with pathological T4, we selected those with pathological stage IIa. Furthermore, we included patients with pathological stage IIIa, regardless of whether they received subsequent chemotherapy. We defined low-risk features as the absence of the following clinicopathological characteristics: poorly differentiated histology, lymphatic/vascular invasion, inadequate lymph node harvest (< 12), bowel obstruction, perineural invasion, localized perforation, and positive surgical margins.(13) Ultimately, only stage IIa patients with low-risk features were included in the study. UFT is an orally administered chemotherapeutic drug combining tegafur and uracil in a 1:4 ratio. Tegafur is a prodrug of 5-FU, while uracil enhances the effect of 5-FU by inhibiting its breakdown by dihydropyrimidine dehydrogenase. This combination provides stable 5-FU plasma levels with low toxicity, making it suitable for metronomic chemotherapy. UFT was the most commonly used ACT for stage II CRC in the past decade. Treatment typically began 4–6 weeks postoperatively, with a dose of 300–350 mg/m²/day administered in 2–3 divided doses. If a patient was unable to tolerate the therapy, the dosage was reduced to 80%. If tolerance was still an issue, the dose was further reduced by 20%, and treatment was discontinued if adverse effects persisted. Patients who tolerated the side effects were encouraged to continue UFT for at least six months. The adverse effects of UFT were categorized as gastrointestinal tract side effects, dizziness, fatigue, mucositis, leukopenia, and skin rash. Gastrointestinal-tract–related side effects included abdominal pain, nausea/vomiting, and diarrhea. The severity of adverse effects was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). The patients were divided into two groups based on whether or not they received ACT (UFT group vs no ACT group). Neither the NCCN nor European Society for Medical Oncology guidelines specifically recommend ACT for low-risk stage IIa patients. Therefore, in our hospital, the decision to administer ACT was based on the clinical physician’s discretion or shared decision-making with the patient. Data collected included each patient's clinical characteristics, OS, progression-free survival (PFS), adverse effects of ACT, and duration of treatment. Disease progression was determined based on imaging reports and interpreted using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline 1.1. Statistical Analysis Data were retrospectively collected from the hospital’s database. Continuous data are presented as the median and compared using the Kruskal–Wallis test. Categorical data are presented as numbers and percentages and were analyzed using the Chi-square test. Survival curves were estimated using the Kaplan–Meier method, and OS was compared between the UFT group and the No ACT group using the log-rank test. In the subgroup analysis, we used Kaplan-Meier curves and the log-rank test to compare OS between three groups: UFT treatment for less than one year, UFT treatment for one year, and observation alone. Receiver Operating Characteristic (ROC) curve analysis was performed to determine the optimal duration of UFT treatment that significantly improves OS, identifying the threshold duration that maximizes sensitivity and specificity for predicting survival outcomes. All statistical analyses were conducted using Statistical Product and Service Solutions (SPSS), version 22 (IBM Corp., Armonk, NY, USA). Results From 2010 to 2019, we collected data from 873 patients who met the criteria for stage II colon cancer. After excluding those who received oral capecitabine or intravenous 5-FU +/- oxaliplatin, as well as patients with pathological T4, we were left with 706 stage IIa patients. Based on clinicopathological characteristics, we further narrowed the cohort to 463 low-risk stage IIa colon cancer patients. Of these, 216 were categorized into the UFT group and 247 into the no ACT group (Fig. 1 ). No significant differences were observed between the UFT and no ACT groups in terms of age, sex, body mass index, Eastern Cooperative Oncology Group (ECOG) performance status, or primary tumor side. The duration of UFT use was less than 6 months for 39 patients (18.6%), at least 6 months but less than 1 year for 54 patients (25%), at least 1 year but less than 2 years for 58 patients (26.85%), and the full 2 years covered by NHI for 65 patients (30.09%) (Table 1 ). Table 1 Low risk stage IIa patients (N = 463) No ACT (n = 247) UFT (n = 216) p value Age 66.8 (54.0-79.3) 64.9 (54.4–74.6) 0.069 Gender 0.768 Female 103 (41.7%) 93 (43.1%) Male 144 (58.3%) 123 (56.9%) BMI 23.4 (19.8–26.4) 23.4 (20.9–26.3) 0.382 ECOG 0.336 0 69 (27.9%) 61 (28.2%) 1 154 (62.3%) 142 (65.7%) 2–3 24 (9.7%) 13 (6.0%) PTS 0.522 Right 80 (32.4%) 64 (29.6%) Left 167 (67.6%) 152 (70.4%) Elevation of Tumor maker 56 (22.7%) 53 (24.5%) 0.643 Diabetes Mellitus 22 (10.2%) 21 (6.0%) 0.763 Coronary artery disease 11 (4.5%) 8 (3.7%) 0.683 Chronic kidney disease 20 (8.1%) 17 (9.7%) 0.927 Duration of UFT < 6 months 39 18.06% < 12 months 54 25% < 24 months 58 26.85% Full 24 months 65 30.09% Chi-square test or Mann-Whitney U test. Median(IQR) * p < 0.05, ** p < 0.01 ACT : Adjuvant chemotherapy, UFT: Tegafur-uracil, BMI: Body mass index, ECOG : Eastern Cooperative Oncology Group, PTS : Primary tumor side. The 5-year PFS rate for the UFT group was 83.9%, and the 5-year OS rate was 87.9% (Fig. 2 ). In contrast, the no ACT group had a 5-year PFS of 71.7% and a 5-year OS of 77%. Both PFS and OS were significantly longer in the UFT group compared to the no ACT group ( p < 0.001). ROC curve analysis conducted within the UFT group revealed that the optimal cut-off point for UFT treatment duration was ≤ 1.74 years, with a sensitivity of 88.9% and a specificity of 38.4%. The area under the curve (AUC) was 0.612 (95% CI, 0.544–0.677), indicating moderate discriminatory ability with statistical significance ( p = 0.035) (Fig. 3 ). Kaplan–Meier curves comparing overall survival between the three groups (UFT treatment for less than one year, UFT treatment for one year, and observation alone) are shown in Fig. 4 . The log-rank (Mantel–Cox) test revealed no significant difference in overall survival between patients administered UFT for less than one year and one year ( p = 0.204). However, both UFT groups showed a significant survival advantage compared to the observation group ( p = 0.020 and p < 0.001, respectively) (Supplementary Table 4). Our analysis for stage IIIa colon cancer included 191 patients. The 5-year OS for these patients was 85.2%, which did not differ significantly from that of stage IIa patients (81.5%; p = 0.277) (Fig. 5 ). We reviewed the adverse events associated with UFT for all stage II patients who received UFT (n = 430). Among these patients, 51 (11.9%) experienced GI-tract–related side effects. Skin rash was the second most common side effect, affecting 20 patients (4.7%). Other side effects, including dizziness, fatigue, mucositis, and leukopenia, had an incidence rate of about 1%. The proportion of patients experiencing grade 3 or higher side effects was only 3.3% (Table 2 ). Table 2 Adverse effect of Tegafur-Uracil Usage UFT patients of all Stage II colon cancer. (N = 430) Grade1-2 ≧Grade3 All GI symptoms 45(10.5%) 8(1.9%) 53(12.4%) Dizziness 3(0.7%) 1(0.2%) 4(0.9%) Fatique 3(0.7%) 0 3(0.7%) Leukopenia 3(0.7%) 0 3(0.7%) Mucoitis 4(0.9%) 1(0.2%) 5(1%) Skin rash 21(4.9%) 5(1%) 26(5.9%) Total 79(18.4%) 14(3.3%) 93(21.7%) Usage UFT patients of all Stage II colon cancer. (N = 430) UFT : Tegafur-Uracil. GI : Gastrointestine. Grading according to CTCAE v5.0 Discussion In this era of rapid advancements in next-generation sequencing, the development of new chemotherapeutic agents and targeted therapies has significantly improved the survival rates and quality of life for cancer patients.(14) However, for CRC, surgery remains the primary curative approach, especially for non-metastatic cases. The progress in immuno-oncology, radiotherapy, and total neoadjuvant therapy for rectal cancer has allowed some patients to preserve organs or achieve improved postoperative outcomes.(15–17) To avoid confounding effects from rectal cancer treatments, this study cohort includes only colon cancer patients. The decision to administer ACT for Stage II CRC is guided by clinicopathological factors such as T4 tumors, poorly differentiated histology, angiolymphatic or perineural invasion, high tumor budding, fewer than 12 sampled lymph nodes, bowel obstruction, and tumor perforation. (18–20) Recent guidelines have added microsatellite instability/stability (MSI/MSS) as a factor in determining treatment strategies. The detection of minimal residual disease through monitoring postoperative circulating tumor DNA has also emerged as a popular topic for prognostication.(21) However, due to incomplete records regarding microsatellite status and limited circulating tumor DNA data at our hospital, these factors were not included in our study. For Stage IIa patients—characterized by T3 tumors without lymph node metastasis—ACT is generally deemed unnecessary if no high-risk features are present, according to current guidelines. Nevertheless, real-world data have shown that the OS of Stage IIIa patients is superior to that of Stage IIa patients. Data from our hospital corroborate this trend, and we believe that this discrepancy is largely due to differences in treatment. According to the Taiwan Cancer Registry, 52% of Stage IIa patients receive postoperative ACT, compared to 82% of Stage IIIa patients.(22) Over the past decade, about half of the Stage IIa patients at our hospital have undergone ACT. Our results demonstrate that the UFT group had significantly better PFS and OS than did the no ACT group ( p < 0.005), underscoring the importance of including ACT in the treatment of low-risk Stage IIa patients. In Taiwan, the NHI covers only 5-FU and UFT for treating Stage II colon cancer. Because 5-FU often requires the placement of a chemoport and a portable infusion device, oral UFT has become the more prevalent option. The most common side effects are GI-related symptoms, with grade 3 or higher adverse events occurring in approximately 3% of cases. Clinically, patients tolerate the treatment well. According to previous studies, the 5-year OS for Stage II colon cancer ranges between 70% and 90%,(23–25) and our findings fall within this range. There is no consensus as to whether low-risk Stage II colon cancer patients require ACT. Some studies advocate for its use,(26) but a 2015 article published in Cancer reported that in low-risk Stage II colon cancer, the 5-year OS was slightly lower in the group that received ACT compared to the group that did not (82.9% vs. 83.3%). 19 That study used a 5-FU-based regimen, with or without oxaliplatin, and the authors speculated that the side effects of chemotherapy might have contributed to the lower OS. In contrast, at our hospital, patients with low-risk Stage IIa colon cancer who received UFT as ACT had a 5-year PFS of 83.9% and a 5-year OS of 87.9%, both significantly higher than those who did not receive ACT ( p < 0.001). The duration of UFT use is limited to two years, as NHI coverage for Stage II CRC in Taiwan was initially approved based on a study conducted over 20 years ago. (27) The NCCN guidelines recommend a duration of approximately six months for ACT, regardless of the regimen. A previous study suggests that the duration of UFT administration as ACT for Stage II CRC should be 16 months.(28) However, a 2015 randomized phase III trial found that six months of postoperative UFT was sufficient for Stage IIB/III colon cancer.(29) In our UFT group, 18% of patients used the drug for less than six months, 25% for 6–12 months, 27% for 12–24 months, and 30% completed the full two-year course (Table 1 ). When using one year as the threshold for analysis, survival curve analysis showed no statistically significant difference between patients who took the drug for one year and those who took it for less than one year. However, the trend suggests that a longer course of treatment may lead to better survival outcomes. ROC curve analysis determined that the optimal cut-off point for UFT treatment duration of was ≤ 1.74 years, with an AUC of 0.612, indicating moderate discriminatory ability. While this finding suggests that the duration of UFT treatment could be a predictive marker for OS, its relatively low specificity limits its diagnostic accuracy. Although the survival curves do not differ significantly in OS between patients who took UFT for more than one year and those who took it for less than one year ( p = 0.204), the data suggest a slight survival advantage for those who took UFT for at least one year. Therefore, we recommend continuing UFT for at least one year in patients with good tolerance, as the overall trend indicates potential survival benefits, even if statistical significance is not robust. Ultimately, the decision should be based on clinical judgment and the patient's condition. This study has several limitations. First, as a retrospective study, the decision to administer ACT was likely influenced by the attending physicians' preferences rather than being randomly assigned. Additionally, our hospital's historical records of mismatch repair protein and microsatellite status were incomplete, preventing us from assessing their impact on prognosis. In conclusion, we recommend that all Stage IIa colon cancer patients receive ACT, as it offers benefits for both OS and PFS, with manageable side effects. The optimal duration of treatment may vary depending on the regimen. Future studies should incorporate mismatch repair protein or microsatellite status to further evaluate their prognostic impact. Declarations Ethics approval and consent to participate : This retrospective study protocol was approved by the Institutional Review Board of Taichung Veterans General Hospital, TCVGH-IRB (No.: CE24511C). Consent for publication : All authors have read and approved the final manuscript, and consent to the publication of the manuscript in its entirety. For any images or personal data included, written informed consent for publication was obtained from the individual(s) involved. Availability of data and material : Data can be made available from the corresponding author on reasonable request. Competing interests : The authors declare that they have no conflict of interest. Funding : No funding was received for conducting this study. Authors' contributions : CLL : Conceptualization, Data curation, Methodology, Formal analysis, Writing – original draft. FFC : Supervision, Writing – review & editing. BZL : Data curation, Writing – review & editing. MCC : Data curation, Investigation . CYL : Data curation, Investigation. SCH : Investigation, Writing – review & editing. Acknowledgements : We would like to express our sincere gratitude to the Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan, for their invaluable support and assistance in the statistical analysis for this study. References Taiwan Health Promotion Administration MoHaW. The number of cancer cases among the top ten cancers in Taiwan in 2021 Taiwan2023 [Available from: https://www.mohw.gov.tw/dl-86025-ff6b8a7e-80b9-450c-8810-433fe4f9228b.html. Taiwan Health Promotion Administration MoHaW. The statistical results of the leading causes of death among Taiwanese citizens in 2023. 2023 [Available from: https://www.mohw.gov.tw/dl-89201-c70ee626-4fd3-4f65-831f-202cefff18e5.html. Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394(10207):1467-80. André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350(23):2343-51. Kuebler JP, Wieand HS, O'Connell MJ, Smith RE, Colangelo LH, Yothers G, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25(16):2198-204. Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer: Final Results of the NO16968 Randomized Controlled Phase III Trial. J Clin Oncol. 2015;33(32):3733-40. AJCC Cancer Staging Manual, 6th2002. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471-4. Hari DM, Leung AM, Lee JH, Sim MS, Vuong B, Chiu CG, et al. AJCC Cancer Staging Manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am Coll Surg. 2013;217(2):181-90. Lan YT, Yang SH, Chang SC, Liang WY, Li AF, Wang HS, et al. Analysis of the seventh edition of American Joint Committee on colon cancer staging. Int J Colorectal Dis. 2012;27(5):657-63. National Comprehensive Cancer Network. Colon Cancer (Version 5.2024) 2024 [Available from: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Yu YL, Tseng WK, Liao CK, Yeh CY, Chen HH, Liu YH, et al. Using oral tegafur/uracil (UFT) plus leucovorin as adjuvant chemotherapy in stage II colorectal cancer: a propensity score matching study from Taiwan. BMC Cancer. 2023;23(1):900. Böckelman C, Engelmann BE, Kaprio T, Hansen TF, Glimelius B. Risk of recurrence in patients with colon cancer stage II and III: a systematic review and meta-analysis of recent literature. Acta Oncol. 2015;54(1):5-16. Colomer R, Miranda J, Romero-Laorden N, Hornedo J, González-Cortijo L, Mouron S, et al. Usefulness and real-world outcomes of next generation sequencing testing in patients with cancer: an observational study on the impact of selection based on clinical judgement. EClinicalMedicine. 2023;60:102029. Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):29-42. Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(5):702-15. Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, et al. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022;386(25):2363-76. Artac M, Turhal NS, Kocer M, Karabulut B, Bozcuk H, Yalcin S, et al. Do high-risk features support the use of adjuvant chemotherapy in stage II colon cancer? A Turkish Oncology Group study. Tumori. 2014;100(2):143-8. Kumar A, Kennecke HF, Renouf DJ, Lim HJ, Gill S, Woods R, et al. Adjuvant chemotherapy use and outcomes of patients with high-risk versus low-risk stage II colon cancer. Cancer. 2015;121(4):527-34. Casadaban L, Rauscher G, Aklilu M, Villenes D, Freels S, Maker AV. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer. Cancer. 2016;122(21):3277-87. Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, et al. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. N Engl J Med. 2022;386(24):2261-72. Center TCR. Republic of China Year 110, Long Form Declaration: Statistics on the Stages and Treatment Methods for 16 Types of Cancer 2024 [Available from: https://twcr.tw/wp-content/uploads/2024/01/CA16_LF110.pdf. Wells KO, Hawkins AT, Krishnamurthy DM, Dharmarajan S, Glasgow SC, Hunt SR, et al. Omission of Adjuvant Chemotherapy Is Associated With Increased Mortality in Patients With T3N0 Colon Cancer With Inadequate Lymph Node Harvest. Diseases of the Colon & Rectum. 2017;60(1):15-21. Lee MW, Kim JS, Kim JY, Lee KH. Prognostic Factor and Survival Benefit of Adjuvant Chemotherapy in Stage IIA Colon Cancer. Ann Coloproctol. 2021;37(1):35-43. Hu J-M, Chou Y-C, Wu C-C, Hsiao C-W, Lee C-C, Chen C-T, et al. Adjuvant chemotherapy with tegafur/uracil for more than 1 year improves disease-free survival for low-risk Stage II colon cancer. Journal of the Chinese Medical Association. 2016;79(9):477-88. Chen PH, Jhou HJ, Chung CH, Wu YY, Huang TC, Lee CH, et al. Benefit of Uracil-Tegafur Used as a Postoperative Adjuvant Chemotherapy for Stage IIA Colon Cancer. Medicina (Kaunas). 2022;59(1). Kato T, Ohashi Y, Nakazato H, Koike A, Saji S, Suzuki H, et al. Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer: multicenter prospective randomized trial. Langenbecks Arch Surg. 2002;386(8):575-81. Chen TC, Jeng YM, Liang JT. Metronomic chemotherapy with tegafur-uracil following radical resection in stage II colorectal cancer. J Formos Med Assoc. 2021;120(5):1194-201. Sadahiro S, Tsuchiya T, Sasaki K, Kondo K, Katsumata K, Nishimura G, et al. Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502. Ann Oncol. 2015;26(11):2274-80. Additional Declarations No competing interests reported. Supplementary Files supplement1.docx supplement2.docx supplement3.docx supplement4.docx supplement5.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-5816207","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":402509123,"identity":"c5ab995a-9770-4ecd-ba1f-037473b08721","order_by":0,"name":"Chang-Lin Lin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYDCCA4yNDz7+k5Dj528+AORKyBChhbnZcAabhbHkjGMJIC08RGhhb5PmYatI3HAgxwDEJ6yF7/jBNskZPBKMDQfOfH51o8aCh4H98NEN+LRInklstvggIcHM2Ny7zTrnGNBhPGlpN/BpMbjB2HhzhoEEGzPD2W3GOWxALRI8ZoS0NEjzJEjwsDHkPDPO+UecliZpngMSQKU5zI9z24jQAvKL4cwGCQMJiWNmzLl9QOsI+YXv+PGHDz421NXvP9/8+HPOtzo5fvbDx/BqQQZsEmCSWOUgwPyBFNWjYBSMglEwcgAADzNL0Ixa2sMAAAAASUVORK5CYII=","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Chang-Lin","middleName":"","lastName":"Lin","suffix":""},{"id":402509124,"identity":"f5711b09-d783-46b6-a1c8-e7c85270182c","order_by":1,"name":"Feng-Fan Chiang","email":"","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Feng-Fan","middleName":"","lastName":"Chiang","suffix":""},{"id":402509125,"identity":"643b88d3-daae-4fce-bbf2-94ebd31edbc8","order_by":2,"name":"Bo-Zh Lin","email":"","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bo-Zh","middleName":"","lastName":"Lin","suffix":""},{"id":402509126,"identity":"1378bd16-44ae-49d1-8ead-aaf17e6b62eb","order_by":3,"name":"Ming-Cheng Chen","email":"","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ming-Cheng","middleName":"","lastName":"Chen","suffix":""},{"id":402509127,"identity":"bebd3d11-9446-48ca-9ead-e784c9586670","order_by":4,"name":"Chun-Yu Lin","email":"","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chun-Yu","middleName":"","lastName":"Lin","suffix":""},{"id":402509128,"identity":"345541c6-c60f-488b-b7ad-05d4c88ca142","order_by":5,"name":"Shang-Chih Huang","email":"","orcid":"","institution":"China Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shang-Chih","middleName":"","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2025-01-13 03:08:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5816207/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5816207/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74050442,"identity":"f2e5daaa-2399-4c64-bdf7-0e6ebafaf967","added_by":"auto","created_at":"2025-01-17 09:51:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":139507,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart for patient selection\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5816207/v1/ca68283464095b4baee2dd9e.png"},{"id":74050235,"identity":"847d0349-c4ee-4bec-8ee4-e93bc972ec9c","added_by":"auto","created_at":"2025-01-17 09:43:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":478127,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival (OS) and progression free survival (PFS) between No ACT group and UFT group.\u003c/p\u003e\n\u003cp\u003eACT, adjuvant chemotherapy; UFT, tegafur-uracil.\u003c/p\u003e\n\u003cp\u003eNo ACT group: 5-year PFS, 71.7%; OS, 77%\u003c/p\u003e\n\u003cp\u003eUFT group: 5-year PFS, 83.9%; OS, 87.9%\u003c/p\u003e\n\u003cp\u003eAdditional detailed data can be found in Supplementary Tables 1 and 2.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5816207/v1/4ec6bbf2c01bdd6f547bb883.png"},{"id":74050443,"identity":"c251a3ff-9c6c-4912-a025-6f48d613b797","added_by":"auto","created_at":"2025-01-17 09:51:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":139954,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for UFT treatment duration and overall survival in low-risk stage IIa colon cancer patients.\u003c/p\u003e\n\u003cp\u003eAUC, \u0026nbsp;area under the curve; ROC, receiver operating characteristic; UFT, \u0026nbsp;tegafur-uracil; optimal cutoff ≤1.77; sensitivity, 88.9%; specificity, 38.4%\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5816207/v1/d1f78c05856b836cb7de4b98.png"},{"id":74050243,"identity":"e0688395-87ce-4578-b6ac-8c08a131b8b1","added_by":"auto","created_at":"2025-01-17 09:43:07","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":222547,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival according to duration of UFT use\u003c/p\u003e\n\u003cp\u003eUFT, tegafur-uracil. Additional information on survival rates and censored data can be found in Supplementary Table 3.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5816207/v1/c35957febfb32385929db8a4.png"},{"id":74050241,"identity":"fc824495-bb36-4c75-bd82-1846d3e309f5","added_by":"auto","created_at":"2025-01-17 09:43:07","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":177208,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of overall survival between Stage IIIa and Stage IIa patients.\u003c/p\u003e\n\u003cp\u003eUFT, tegafur-uracil; Additional detailed data can be found in Supplementary Table 5.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-5816207/v1/cf5d207c596ccb5ebb55d349.png"},{"id":94063607,"identity":"eda1c07d-10bc-48cb-8d75-85f5e834a646","added_by":"auto","created_at":"2025-10-22 07:23:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1705438,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5816207/v1/b3bf8187-b8c9-4c2b-a5f0-947b8252cfdc.pdf"},{"id":74050234,"identity":"ef8be1b5-bb8b-4633-9bf2-adab89a9d509","added_by":"auto","created_at":"2025-01-17 09:43:07","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16083,"visible":true,"origin":"","legend":"","description":"","filename":"supplement1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5816207/v1/82c3d81ab8c876192ab4063a.docx"},{"id":74050236,"identity":"795e7428-89e0-41ed-9693-21222274fc44","added_by":"auto","created_at":"2025-01-17 09:43:07","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":141511,"visible":true,"origin":"","legend":"","description":"","filename":"supplement2.docx","url":"https://assets-eu.researchsquare.com/files/rs-5816207/v1/0de9f4bc24b559fcf33bf69e.docx"},{"id":74050444,"identity":"4061a5a0-8bad-4302-8faa-127b28145530","added_by":"auto","created_at":"2025-01-17 09:51:07","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":14606,"visible":true,"origin":"","legend":"","description":"","filename":"supplement3.docx","url":"https://assets-eu.researchsquare.com/files/rs-5816207/v1/1f3d257bab0ff197a6060305.docx"},{"id":74050240,"identity":"511439e3-27ac-42be-8cfc-2ff20d6e66c6","added_by":"auto","created_at":"2025-01-17 09:43:07","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":14098,"visible":true,"origin":"","legend":"","description":"","filename":"supplement4.docx","url":"https://assets-eu.researchsquare.com/files/rs-5816207/v1/2b53a935c80009b64795f8df.docx"},{"id":74050251,"identity":"4941e205-0c08-49e2-bb8d-7b02480e0ea8","added_by":"auto","created_at":"2025-01-17 09:43:07","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":16398,"visible":true,"origin":"","legend":"","description":"","filename":"supplement5.docx","url":"https://assets-eu.researchsquare.com/files/rs-5816207/v1/06e4fab59517aa64036f5abf.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluating the Benefits of Tegafur-Uracil Adjuvant Therapy in Low-Risk Stage IIa Colon Cancer: Insights from a Decade-Long Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eColorectal cancer (CRC) has consistently ranked among the top two cancers in terms of incidence in Taiwan and was the third leading cause of death in 2023. (1, 2) Current treatment for CRC is primarily guided by the American Joint Committee on Cancer (AJCC) staging system, with curative surgery remaining the gold standard for non-metastatic CRC.(3) Patients with Stage I CRC typically require no adjuvant chemotherapy (ACT) and are only advised to undergo regular post-surgery follow-up. For Stage III patients, evidence from three landmark trials\u0026mdash;MOSAIC, NSABP C-07, and NO16968/XELOXA(4\u0026ndash;6)\u0026mdash;supports the recommendation of doublet ACT to improve oncological outcomes following surgery. However, the benefit of ACT for Stage II patients has been a topic of debate, with varying opinions on whether it improves long-term outcomes.\u003c/p\u003e \u003cp\u003eAccording to the AJCC staging system, tumors classified as T3 or higher without regional lymph node metastasis are considered Stage II. Regardless of T stage, tumors with regional lymph node metastasis but without distant metastasis are categorized as Stage III. Both Stage II and III are further subdivided into a, b, and c groups for more precise classification. Since the AJCC 6th edition, T3N0 has been specifically classified as Stage IIa,(7) while T1-2N1a and -N1c are categorized as Stage IIIa. In the AJCC 7th edition, T1N2a was newly added to Stage IIIa.(8)\u003c/p\u003e \u003cp\u003eThe distinction between Stage IIIa and Stage IIa is noteworthy because some real-world data indicate that the five-year overall survival (OS) for Stage IIIa is longer than that for Stage IIa.(9) A 2012 study published in the International Journal of Colorectal Disease reported a five-year OS rate of 85.4% for Stage IIIa, compared to 79.7% for Stage IIa.(10) These findings suggest that Stage IIa patients might require more aggressive postoperative treatment.\u003c/p\u003e \u003cp\u003e According to the National Comprehensive Cancer Network (NCCN) guidelines, ACT options for Stage II colon cancer include 5-FU, oxaliplatin, and capecitabine.(11) However, in Taiwan, oxaliplatin and capecitabine are not covered by national health insurance (NHI) for Stage II colon cancer, leaving oral tegafur-uracil (UFT) as the primary ACT option.(12) NHI coverage for UFT extends up to two years. Currently, the guidelines do not clearly state whether ACT offers a survival benefit for Stage IIa colon cancer.\u003c/p\u003e \u003cp\u003eThis article presents a retrospective analysis of a decade\u0026rsquo;s worth of data from a single hospital, investigating whether the use of UFT for ACT improves the long-term outcomes for Stage IIa colon cancer patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eData for this retrospective study were collected from the Taichung Veterans General Hospital Cancer Registry for all newly diagnosed CRC patients between 2010 and 2019. We included only patients who underwent curative surgery and were diagnosed with pathological stage II colon cancer. Rectal cancer was excluded because it often involves neoadjuvant therapy. Patients who died from surgical complications or had synchronous distant metastases were excluded. We defined \"synchronous distant metastases\" as metastases detected within six months of surgery. Additionally, patients who received oral capecitabine or intravenous 5-FU with or without oxaliplatin were excluded. After excluding patients with pathological T4, we selected those with pathological stage IIa. Furthermore, we included patients with pathological stage IIIa, regardless of whether they received subsequent chemotherapy.\u003c/p\u003e \u003cp\u003eWe defined low-risk features as the absence of the following clinicopathological characteristics: poorly differentiated histology, lymphatic/vascular invasion, inadequate lymph node harvest (\u0026lt;\u0026thinsp;12), bowel obstruction, perineural invasion, localized perforation, and positive surgical margins.(13) Ultimately, only stage IIa patients with low-risk features were included in the study.\u003c/p\u003e \u003cp\u003eUFT is an orally administered chemotherapeutic drug combining tegafur and uracil in a 1:4 ratio. Tegafur is a prodrug of 5-FU, while uracil enhances the effect of 5-FU by inhibiting its breakdown by dihydropyrimidine dehydrogenase. This combination provides stable 5-FU plasma levels with low toxicity, making it suitable for metronomic chemotherapy.\u003c/p\u003e \u003cp\u003eUFT was the most commonly used ACT for stage II CRC in the past decade. Treatment typically began 4\u0026ndash;6 weeks postoperatively, with a dose of 300\u0026ndash;350 mg/m\u0026sup2;/day administered in 2\u0026ndash;3 divided doses. If a patient was unable to tolerate the therapy, the dosage was reduced to 80%. If tolerance was still an issue, the dose was further reduced by 20%, and treatment was discontinued if adverse effects persisted. Patients who tolerated the side effects were encouraged to continue UFT for at least six months.\u003c/p\u003e \u003cp\u003eThe adverse effects of UFT were categorized as gastrointestinal tract side effects, dizziness, fatigue, mucositis, leukopenia, and skin rash. Gastrointestinal-tract\u0026ndash;related side effects included abdominal pain, nausea/vomiting, and diarrhea. The severity of adverse effects was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0).\u003c/p\u003e \u003cp\u003eThe patients were divided into two groups based on whether or not they received ACT (UFT group vs no ACT group). Neither the NCCN nor European Society for Medical Oncology guidelines specifically recommend ACT for low-risk stage IIa patients. Therefore, in our hospital, the decision to administer ACT was based on the clinical physician\u0026rsquo;s discretion or shared decision-making with the patient.\u003c/p\u003e \u003cp\u003eData collected included each patient's clinical characteristics, OS, progression-free survival (PFS), adverse effects of ACT, and duration of treatment. Disease progression was determined based on imaging reports and interpreted using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline 1.1.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were retrospectively collected from the hospital\u0026rsquo;s database. Continuous data are presented as the median and compared using the Kruskal\u0026ndash;Wallis test. Categorical data are presented as numbers and percentages and were analyzed using the Chi-square test. Survival curves were estimated using the Kaplan\u0026ndash;Meier method, and OS was compared between the UFT group and the No ACT group using the log-rank test. In the subgroup analysis, we used Kaplan-Meier curves and the log-rank test to compare OS between three groups: UFT treatment for less than one year, UFT treatment for one year, and observation alone.\u003c/p\u003e \u003cp\u003eReceiver Operating Characteristic (ROC) curve analysis was performed to determine the optimal duration of UFT treatment that significantly improves OS, identifying the threshold duration that maximizes sensitivity and specificity for predicting survival outcomes. All statistical analyses were conducted using Statistical Product and Service Solutions (SPSS), version 22 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eFrom 2010 to 2019, we collected data from 873 patients who met the criteria for stage II colon cancer. After excluding those who received oral capecitabine or intravenous 5-FU +/- oxaliplatin, as well as patients with pathological T4, we were left with 706 stage IIa patients. Based on clinicopathological characteristics, we further narrowed the cohort to 463 low-risk stage IIa colon cancer patients. Of these, 216 were categorized into the UFT group and 247 into the no ACT group (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). No significant differences were observed between the UFT and no ACT groups in terms of age, sex, body mass index, Eastern Cooperative Oncology Group (ECOG) performance status, or primary tumor side. The duration of UFT use was less than 6 months for 39 patients (18.6%), at least 6 months but less than 1 year for 54 patients (25%), at least 1 year but less than 2 years for 58 patients (26.85%), and the full 2 years covered by NHI for 65 patients (30.09%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLow risk stage IIa patients (N\u0026thinsp;=\u0026thinsp;463)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo ACT (n\u0026thinsp;=\u0026thinsp;247)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eUFT (n\u0026thinsp;=\u0026thinsp;216)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(54.0-79.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(54.4\u0026ndash;74.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.768\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(43.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(58.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(56.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(19.8\u0026ndash;26.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(20.9\u0026ndash;26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.382\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.336\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(27.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(28.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e154\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(62.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(65.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(9.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(6.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.522\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(32.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(29.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(67.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(70.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevation of Tumor maker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(22.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(24.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.643\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes Mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(10.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(6.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.763\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary artery disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(4.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(3.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.683\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic kidney disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(8.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(9.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.927\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of UFT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18.06%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;12 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;24 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.85%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFull 24 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.09%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eChi-square test or Mann-Whitney U test. Median(IQR) *\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, **\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eACT : Adjuvant chemotherapy, UFT: Tegafur-uracil, BMI: Body mass index, ECOG : Eastern Cooperative Oncology Group, PTS : Primary tumor side.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe 5-year PFS rate for the UFT group was 83.9%, and the 5-year OS rate was 87.9% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In contrast, the no ACT group had a 5-year PFS of 71.7% and a 5-year OS of 77%. Both PFS and OS were significantly longer in the UFT group compared to the no ACT group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). ROC curve analysis conducted within the UFT group revealed that the optimal cut-off point for UFT treatment duration was \u0026le;\u0026thinsp;1.74 years, with a sensitivity of 88.9% and a specificity of 38.4%. The area under the curve (AUC) was 0.612 (95% CI, 0.544\u0026ndash;0.677), indicating moderate discriminatory ability with statistical significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eKaplan\u0026ndash;Meier curves comparing overall survival between the three groups (UFT treatment for less than one year, UFT treatment for one year, and observation alone) are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The log-rank (Mantel\u0026ndash;Cox) test revealed no significant difference in overall survival between patients administered UFT for less than one year and one year (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.204). However, both UFT groups showed a significant survival advantage compared to the observation group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020 and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively) (Supplementary Table\u0026nbsp;4).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOur analysis for stage IIIa colon cancer included 191 patients. The 5-year OS for these patients was 85.2%, which did not differ significantly from that of stage IIa patients (81.5%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.277) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWe reviewed the adverse events associated with UFT for all stage II patients who received UFT (n\u0026thinsp;=\u0026thinsp;430). Among these patients, 51 (11.9%) experienced GI-tract\u0026ndash;related side effects. Skin rash was the second most common side effect, affecting 20 patients (4.7%). Other side effects, including dizziness, fatigue, mucositis, and leukopenia, had an incidence rate of about 1%. The proportion of patients experiencing grade 3 or higher side effects was only 3.3% (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdverse effect of Tegafur-Uracil\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUsage UFT patients of all Stage II colon cancer. (N\u0026thinsp;=\u0026thinsp;430)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGrade1-2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e≧Grade3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGI symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45(10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53(12.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDizziness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(0.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(0.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatique\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(0.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(0.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(0.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(0.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucoitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin rash\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(4.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79(18.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(3.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93(21.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eUsage UFT patients of all Stage II colon cancer. (N\u0026thinsp;=\u0026thinsp;430)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eUFT : Tegafur-Uracil. GI : Gastrointestine.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eGrading according to CTCAE v5.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this era of rapid advancements in next-generation sequencing, the development of new chemotherapeutic agents and targeted therapies has significantly improved the survival rates and quality of life for cancer patients.(14) However, for CRC, surgery remains the primary curative approach, especially for non-metastatic cases. The progress in immuno-oncology, radiotherapy, and total neoadjuvant therapy for rectal cancer has allowed some patients to preserve organs or achieve improved postoperative outcomes.(15\u0026ndash;17) To avoid confounding effects from rectal cancer treatments, this study cohort includes only colon cancer patients.\u003c/p\u003e \u003cp\u003eThe decision to administer ACT for Stage II CRC is guided by clinicopathological factors such as T4 tumors, poorly differentiated histology, angiolymphatic or perineural invasion, high tumor budding, fewer than 12 sampled lymph nodes, bowel obstruction, and tumor perforation. (18\u0026ndash;20) Recent guidelines have added microsatellite instability/stability (MSI/MSS) as a factor in determining treatment strategies. The detection of minimal residual disease through monitoring postoperative circulating tumor DNA has also emerged as a popular topic for prognostication.(21) However, due to incomplete records regarding microsatellite status and limited circulating tumor DNA data at our hospital, these factors were not included in our study.\u003c/p\u003e \u003cp\u003e For Stage IIa patients\u0026mdash;characterized by T3 tumors without lymph node metastasis\u0026mdash;ACT is generally deemed unnecessary if no high-risk features are present, according to current guidelines. Nevertheless, real-world data have shown that the OS of Stage IIIa patients is superior to that of Stage IIa patients. Data from our hospital corroborate this trend, and we believe that this discrepancy is largely due to differences in treatment. According to the Taiwan Cancer Registry, 52% of Stage IIa patients receive postoperative ACT, compared to 82% of Stage IIIa patients.(22) Over the past decade, about half of the Stage IIa patients at our hospital have undergone ACT. Our results demonstrate that the UFT group had significantly better PFS and OS than did the no ACT group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.005), underscoring the importance of including ACT in the treatment of low-risk Stage IIa patients.\u003c/p\u003e \u003cp\u003eIn Taiwan, the NHI covers only 5-FU and UFT for treating Stage II colon cancer. Because 5-FU often requires the placement of a chemoport and a portable infusion device, oral UFT has become the more prevalent option. The most common side effects are GI-related symptoms, with grade 3 or higher adverse events occurring in approximately 3% of cases. Clinically, patients tolerate the treatment well.\u003c/p\u003e \u003cp\u003eAccording to previous studies, the 5-year OS for Stage II colon cancer ranges between 70% and 90%,(23\u0026ndash;25) and our findings fall within this range. There is no consensus as to whether low-risk Stage II colon cancer patients require ACT. Some studies advocate for its use,(26) but a 2015 article published in \u003cem\u003eCancer\u003c/em\u003e reported that in low-risk Stage II colon cancer, the 5-year OS was slightly lower in the group that received ACT compared to the group that did not (82.9% vs. 83.3%).\u003csup\u003e19\u003c/sup\u003e That study used a 5-FU-based regimen, with or without oxaliplatin, and the authors speculated that the side effects of chemotherapy might have contributed to the lower OS. In contrast, at our hospital, patients with low-risk Stage IIa colon cancer who received UFT as ACT had a 5-year PFS of 83.9% and a 5-year OS of 87.9%, both significantly higher than those who did not receive ACT (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eThe duration of UFT use is limited to two years, as NHI coverage for Stage II CRC in Taiwan was initially approved based on a study conducted over 20 years ago. (27) The NCCN guidelines recommend a duration of approximately six months for ACT, regardless of the regimen. A previous study suggests that the duration of UFT administration as ACT for Stage II CRC should be 16 months.(28) However, a 2015 randomized phase III trial found that six months of postoperative UFT was sufficient for Stage IIB/III colon cancer.(29) In our UFT group, 18% of patients used the drug for less than six months, 25% for 6\u0026ndash;12 months, 27% for 12\u0026ndash;24 months, and 30% completed the full two-year course (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). When using one year as the threshold for analysis, survival curve analysis showed no statistically significant difference between patients who took the drug for one year and those who took it for less than one year. However, the trend suggests that a longer course of treatment may lead to better survival outcomes. ROC curve analysis determined that the optimal cut-off point for UFT treatment duration of was \u0026le;\u0026thinsp;1.74 years, with an AUC of 0.612, indicating moderate discriminatory ability. While this finding suggests that the duration of UFT treatment could be a predictive marker for OS, its relatively low specificity limits its diagnostic accuracy.\u003c/p\u003e \u003cp\u003eAlthough the survival curves do not differ significantly in OS between patients who took UFT for more than one year and those who took it for less than one year (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.204), the data suggest a slight survival advantage for those who took UFT for at least one year. Therefore, we recommend continuing UFT for at least one year in patients with good tolerance, as the overall trend indicates potential survival benefits, even if statistical significance is not robust. Ultimately, the decision should be based on clinical judgment and the patient's condition.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, as a retrospective study, the decision to administer ACT was likely influenced by the attending physicians' preferences rather than being randomly assigned. Additionally, our hospital's historical records of mismatch repair protein and microsatellite status were incomplete, preventing us from assessing their impact on prognosis.\u003c/p\u003e \u003cp\u003eIn conclusion, we recommend that all Stage IIa colon cancer patients receive ACT, as it offers benefits for both OS and PFS, with manageable side effects. The optimal duration of treatment may vary depending on the regimen. Future studies should incorporate mismatch repair protein or microsatellite status to further evaluate their prognostic impact.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study protocol was approved by the Institutional Review Board of Taichung Veterans General Hospital, TCVGH-IRB (No.: CE24511C).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the final manuscript, and consent to the publication of the manuscript in its entirety. For any images or personal data included, written informed consent for publication was obtained from the individual(s) involved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData can be made available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for conducting this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCLL\u003c/strong\u003e : Conceptualization, Data curation, Methodology, Formal analysis, Writing \u0026ndash; original draft. \u003cstrong\u003eFFC\u003c/strong\u003e : Supervision, Writing \u0026ndash; review \u0026amp; editing. \u003cstrong\u003eBZL\u003c/strong\u003e : Data curation, Writing \u0026ndash; review \u0026amp; editing. \u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003cstrong\u003eMCC\u003c/strong\u003e : Data curation, Investigation\u003csup\u003e.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003eCYL\u003c/strong\u003e : Data curation, Investigation. \u003cstrong\u003eSCH\u003c/strong\u003e : Investigation, Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to express our sincere gratitude to the Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan, for their invaluable support and assistance in the statistical analysis for this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTaiwan Health Promotion Administration MoHaW. The number of cancer cases among the top ten cancers in Taiwan in 2021 Taiwan2023 [Available from: https://www.mohw.gov.tw/dl-86025-ff6b8a7e-80b9-450c-8810-433fe4f9228b.html.\u003c/li\u003e\n\u003cli\u003eTaiwan Health Promotion Administration MoHaW. The statistical results of the leading causes of death among Taiwanese citizens in 2023. 2023 [Available from: https://www.mohw.gov.tw/dl-89201-c70ee626-4fd3-4f65-831f-202cefff18e5.html.\u003c/li\u003e\n\u003cli\u003eDekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394(10207):1467-80.\u003c/li\u003e\n\u003cli\u003eAndr\u0026eacute; T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350(23):2343-51.\u003c/li\u003e\n\u003cli\u003eKuebler JP, Wieand HS, O\u0026apos;Connell MJ, Smith RE, Colangelo LH, Yothers G, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25(16):2198-204.\u003c/li\u003e\n\u003cli\u003eSchmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer: Final Results of the NO16968 Randomized Controlled Phase III Trial. J Clin Oncol. 2015;33(32):3733-40.\u003c/li\u003e\n\u003cli\u003eAJCC Cancer Staging Manual, 6th2002.\u003c/li\u003e\n\u003cli\u003eEdge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471-4.\u003c/li\u003e\n\u003cli\u003eHari DM, Leung AM, Lee JH, Sim MS, Vuong B, Chiu CG, et al. AJCC Cancer Staging Manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am Coll Surg. 2013;217(2):181-90.\u003c/li\u003e\n\u003cli\u003eLan YT, Yang SH, Chang SC, Liang WY, Li AF, Wang HS, et al. Analysis of the seventh edition of American Joint Committee on colon cancer staging. Int J Colorectal Dis. 2012;27(5):657-63.\u003c/li\u003e\n\u003cli\u003eNational Comprehensive Cancer Network. Colon Cancer (Version 5.2024) 2024 [Available from: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf.\u003c/li\u003e\n\u003cli\u003eYu YL, Tseng WK, Liao CK, Yeh CY, Chen HH, Liu YH, et al. Using oral tegafur/uracil (UFT) plus leucovorin as adjuvant chemotherapy in stage II colorectal cancer: a propensity score matching study from Taiwan. BMC Cancer. 2023;23(1):900.\u003c/li\u003e\n\u003cli\u003eB\u0026ouml;ckelman C, Engelmann BE, Kaprio T, Hansen TF, Glimelius B. Risk of recurrence in patients with colon cancer stage II and III: a systematic review and meta-analysis of recent literature. Acta Oncol. 2015;54(1):5-16.\u003c/li\u003e\n\u003cli\u003eColomer R, Miranda J, Romero-Laorden N, Hornedo J, Gonz\u0026aacute;lez-Cortijo L, Mouron S, et al. Usefulness and real-world outcomes of next generation sequencing testing in patients with cancer: an observational study on the impact of selection based on clinical judgement. EClinicalMedicine. 2023;60:102029.\u003c/li\u003e\n\u003cli\u003eBahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):29-42.\u003c/li\u003e\n\u003cli\u003eConroy T, Bosset JF, Etienne PL, Rio E, Fran\u0026ccedil;ois \u0026Eacute;, Mesgouez-Nebout N, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(5):702-15.\u003c/li\u003e\n\u003cli\u003eCercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, et al. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022;386(25):2363-76.\u003c/li\u003e\n\u003cli\u003eArtac M, Turhal NS, Kocer M, Karabulut B, Bozcuk H, Yalcin S, et al. Do high-risk features support the use of adjuvant chemotherapy in stage II colon cancer? A Turkish Oncology Group study. Tumori. 2014;100(2):143-8.\u003c/li\u003e\n\u003cli\u003eKumar A, Kennecke HF, Renouf DJ, Lim HJ, Gill S, Woods R, et al. Adjuvant chemotherapy use and outcomes of patients with high-risk versus low-risk stage II colon cancer. Cancer. 2015;121(4):527-34.\u003c/li\u003e\n\u003cli\u003eCasadaban L, Rauscher G, Aklilu M, Villenes D, Freels S, Maker AV. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer. Cancer. 2016;122(21):3277-87.\u003c/li\u003e\n\u003cli\u003eTie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, et al. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. N Engl J Med. 2022;386(24):2261-72.\u003c/li\u003e\n\u003cli\u003eCenter TCR. Republic of China Year 110, Long Form Declaration: Statistics on the Stages and Treatment Methods for 16 Types of Cancer 2024 [Available from: https://twcr.tw/wp-content/uploads/2024/01/CA16_LF110.pdf.\u003c/li\u003e\n\u003cli\u003eWells KO, Hawkins AT, Krishnamurthy DM, Dharmarajan S, Glasgow SC, Hunt SR, et al. Omission of Adjuvant Chemotherapy Is Associated With Increased Mortality in Patients With T3N0 Colon Cancer With Inadequate Lymph Node Harvest. Diseases of the Colon \u0026amp; Rectum. 2017;60(1):15-21.\u003c/li\u003e\n\u003cli\u003eLee MW, Kim JS, Kim JY, Lee KH. Prognostic Factor and Survival Benefit of Adjuvant Chemotherapy in Stage IIA Colon Cancer. Ann Coloproctol. 2021;37(1):35-43.\u003c/li\u003e\n\u003cli\u003eHu J-M, Chou Y-C, Wu C-C, Hsiao C-W, Lee C-C, Chen C-T, et al. Adjuvant chemotherapy with tegafur/uracil for more than 1 year improves disease-free survival for low-risk Stage II colon cancer. Journal of the Chinese Medical Association. 2016;79(9):477-88.\u003c/li\u003e\n\u003cli\u003eChen PH, Jhou HJ, Chung CH, Wu YY, Huang TC, Lee CH, et al. Benefit of Uracil-Tegafur Used as a Postoperative Adjuvant Chemotherapy for Stage IIA Colon Cancer. Medicina (Kaunas). 2022;59(1).\u003c/li\u003e\n\u003cli\u003eKato T, Ohashi Y, Nakazato H, Koike A, Saji S, Suzuki H, et al. Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer: multicenter prospective randomized trial. Langenbecks Arch Surg. 2002;386(8):575-81.\u003c/li\u003e\n\u003cli\u003eChen TC, Jeng YM, Liang JT. Metronomic chemotherapy with tegafur-uracil following radical resection in stage II colorectal cancer. J Formos Med Assoc. 2021;120(5):1194-201.\u003c/li\u003e\n\u003cli\u003eSadahiro S, Tsuchiya T, Sasaki K, Kondo K, Katsumata K, Nishimura G, et al. Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502. Ann Oncol. 2015;26(11):2274-80.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Tegafur, Adjuvant chemotherapy, Stage IIa colon cancer","lastPublishedDoi":"10.21203/rs.3.rs-5816207/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5816207/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSurgical resection is the gold standard for treating non-metastatic colorectal cancer. The five-year overall survival (OS) for Stage IIIa patients is longer than that for Stage IIa patients, highlighting the importance of adjuvant therapy (ACT) for Stage IIa. This study aims to evaluate the treatment outcomes and prognostic factors for Stage IIa colon cancer at our hospital over the past decade.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003eThis retrospective study was conducted at a medical center and included patients treated between January 1, 2010, and December 31, 2019. We included only patients who underwent surgery and had pathological Stage IIa or IIIa colon cancer. Collected data included patient characteristics, oncological outcomes, receipt of adjuvant therapy, and adverse effects associated with adjuvant therapy.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e \u003cp\u003eWe observed a higher five-year OS for Stage IIIa than Stage IIa patients, but the difference was not statistically significant. Patients who were administered tegafur-uracil had longer five-year progression-free survival and five-year overall survival compared to the No ACT group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005). The receiver operating characteristic curve identified the optimal cut-off point for tegafur-uracil (UFT) duration as \u0026le;\u0026thinsp;1.74 years, with the area under the curve being statistically significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eACT is recommended even for low-risk Stage IIa patients postoperatively. The adverse effects of UFT were generally acceptable, with Grade 3 or higher adverse effects being rare. If UFT is used as an ACT regimen for stage IIa colon cancer, a duration of more than one year is suggested.\u003c/p\u003e","manuscriptTitle":"Evaluating the Benefits of Tegafur-Uracil Adjuvant Therapy in Low-Risk Stage IIa Colon Cancer: Insights from a Decade-Long Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-17 09:43:02","doi":"10.21203/rs.3.rs-5816207/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":"9ac85d1d-0189-4b0d-b63b-023c988621b6","owner":[],"postedDate":"January 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-22T07:23:31+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-17 09:43:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5816207","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5816207","identity":"rs-5816207","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}