What is the impact of the Lymph Node Ratio (LNR) on Overall Survival (OS) in patients with colon cancer?

What is the impact of the Lymph Node Ratio (LNR) on Overall Survival (OS) in patients with colon cancer? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article What is the impact of the Lymph Node Ratio (LNR) on Overall Survival (OS) in patients with colon cancer? Marcin Ekman, Elzbieta Jodłowska-Siewert, Marcin Urbanowicz, Maciej Berut, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6383521/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Apr, 2026 Read the published version in Scientific Reports → Version 1 posted 12 You are reading this latest preprint version Abstract Introduction: Colorectal cancer (CRC) is a major health concern globally, with lymph node metastasis being a key factor in its spread. The Lymph Node Ratio (LNR) – the ratio of pathologically positive lymph nodes to the total number of examined nodes – has emerged as a significant prognostic factor in CRC. Notably, there is a lack of data from prospective cohort studies on this topic. This study aims to investigate the impact of LNR on Overall Survival (OS) in patients with colon cancer, expanding the knowledge on its prognostic value beyond current AJCC TNM classification. Materials and Methods A prospective cohort study was conducted across seven Polish surgical centers enrolling 445 patients with primary colon cancer. The study collected survival data until September 30, 2022, focusing on patients aged 18–75 years eligible for radical surgery. Preoperative assessments included demographic information, Body Mass Index (BMI) and histopathological evaluation according to AJCC 8th edition. Surgical complications were graded using the Clavien-Dindo scale. The relationship between OS and LNR was analyzed using a multivariate Cox proportional hazards model, adjusting for significant covariates. Results In the multivariate Cox model, LNR, BMI and grade III or higher surgical complications were independently associated with overall survival in colon cancer patients. For LNR, a 0.1-unit increase was associated with a 26% increase in the hazard of death over the whole observation period (95% CI: 7–48% increase, p = 0.006 ). Conclusion LNR, along with BMI and the severity of postoperative complications, serves as an independent prognostic factor for OS in colon cancer patients. These results of prospective cohort study support the inclusion of LNR in future oncological staging systems and highlight the importance of comprehensive lymph node analysis in managing colon cancer. Health sciences/Gastroenterology/Gastrointestinal diseases/Gastrointestinal cancer Health sciences/Oncology/Surgical oncology Figures Figure 1 Figure 2 1. INTRODUCTION Colorectal cancer (CRC) remains a significant global health challenge and a leading cause of cancer-related mortality. 1 Among prognostic tools, the TNM (Tumor, Node, Metastasis) classification system, updated to its 8th edition by the American Joint Committee on Cancer (AJCC), stands as the cornerstone for assessing the clinical stage of this disease. 2 – 4 Metastasis to lymph nodes is a key mechanism in the process of cancer spread. 5 , 6 In the AJCC 8th edition TNM classification for colon cancer (CC), the N category is defined by the number of identified metastatic lymph nodes (MLN). 7 While effective in long-term outcome prediction, the TNM system is acknowledged for its limited consideration of critical MLN aspects. Due to its limitations and simplifications, this system does not account for, among other factors, the total number of removed lymph nodes. In the 8th edition of the AJCC Cancer Staging Manual, the Lymph Node Ratio (LNR) in colon cancer prognosis is emphasized as a key additional factor for further evaluation, highlighting its growing significance in prognostic assessments. LNR, defined as the ratio of pathologically positive lymph nodes to the total number of examined nodes, is considered a significant prognostic factor in various malignancies, including breast, pancreatic, thyroid, esophageal, gastric, oropharyngeal, non-small-cell lung, and colorectal cancer. 8 – 16 In these cancers, a high LNR has been significantly correlated with poorer prognosis for patients, indicating its potential as a marker for more intensive treatment and more aggressive post-therapy follow-up. 17 The investigation into the relationship between LNR and survival in stage III colon cancer patients was initially undertaken by Wang J. et al. using data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry. 17 The study found that a higher lymph node ratio (LNR) is associated with poorer survival outcomes in node-positive CC patients and offers superior prognostic information compared to traditional pN staging. Furthermore, the prognostic significance of LNR is particularly notable when fewer than 12 lymph nodes are examined, emphasizing the need for adequate lymph node assessment during surgery. 17 An undeniable limitation of this study was its retrospective nature. 17 Ceelen et al. provided a valuable contribution to the understanding of prognostic factors in CC and CRC through their meta-analysis of 16 studies involving patients with these malignancies. This analysis confirmed that the utilization of LNR as a predictive factor allows better differentiation of this type of cancer compared to the N stage. Furthermore, the cumulative Hazard Ratio (HR) analysis revealed LNR as a significant prognostic factor for overall survival (OS) and for disease-free survival (DFS). 18 The review by Ceelen et al. highlights limitations such as the retrospective nature of included studies and methodological variability, which may impact the findings on the prognostic value of the LNR in stage III CRC. Various authors have debated the utility of the LNR in the context of the minimum number of sampled lymph nodes for analysis. 19 In numerous studies, it has been emphasized that an adequate examination of lymph nodes (> 12) is crucial to maintain the prognostic significance of LNR in stage III colorectal cancer patients. 20 – 23 Current guidelines also specify a minimum of 12 lymph nodes in colon cancer surgery to minimize the false-negative rate of lymph node metastasis and to prevent under-staging. 3 , 4 , 7 This suggests that the extent of lymphadenectomy plays a significant role in patient outcomes, with a higher number of lymph nodes removed being associated with better long-term survival. 24 However, the procedure is not without risks, as expanding lymphadenectomy could lead to complications such as damage to the superior mesenteric vein (SMV), intraoperative bleeding, lymph leakage, sexual dysfunction, and damage to internal organs, with some studies suggesting these risks may not translate into long-term survival benefits. 25 – 27 Given these concerns, the routine performance of Complete Mesocolic Excision (CME) with high vascular ligation, as advocated by some for all colon cancer patients, has been contested. 28 In contrast to previous studies, the above-mentioned authors suggested that LNR has a superior prognostic value compared to the pN category, irrespective of the minimum number of lymph nodes examined. 29 – 32 Furthermore, Macedo et al. emphasize that LNR demonstrates enhanced prognostic utility, particularly in the subgroup of patients with lymphadenectomy extent lower than recommended in the guidelines. 30 Also these studies were retrospective and were limited to colon or rectal III stage cancer. 33 The potential impact of LNR has been observed across different stages of CC, implying its prognostic significance for both early and advanced disease presentations. Fang et. al indicated that the LNR accurately predicts the prognosis of patients with early-stage CC. 34 Li et al., in a study encompassing 389 eligible patients with CRC in stages I-IV, demonstrated that LNR is an independent prognostic factor. However, it is essential to note that this study was limited by its single-center retrospective design. 35 The LNR has been confirmed additionally as an independent prognostic factor in stage IV CC with liver-only metastasis undergoing curative resection. 36 – 38 Interestingly, recent years have seen a growing interest in investigating the log odds of positive lymph nodes (LODDS) as a new prognostic factor. 34 , 35 , 54 – 56 This metric, essentially a mathematical transformation of the LNR, has been explored for its prognostic significance in CC. Beqar et al. demonstrated that the prognostic impact of LODDS is comparable to that of LNR for CC patients, suggesting it does not provide new insights beyond what LNR already offers. 57 Furthermore, the simplicity and ease of calculation argue in favor of using LNR as a straightforward, effective prognostic tool in clinical practice. The aim of this research is a prospective view on LNR as a potential prognostic marker, even though it is not currently recognized in the AJCC 8th edition TNM classification. Due to the limited understanding of LNR's clinical significance in these specific contexts, our multi-center prospective research involves a comprehensive analysis of clinical data. A crucial aspect of our analysis includes utilizing a multivariate Cox proportional hazards model to explore the relationship between overall survival and LNR, incorporating a broad spectrum of influencing factors. Unlike other studies, the model presented in this study also considers surgically relevant aspects such as the patient's Body Mass Index (BMI) and the severity of postoperative complications as classified by the Clavien-Dindo scale. Our research is focusing on patients diagnosed with CC (stage I-III). Although both colon and rectal cancers are classified under CRC, the surgical and oncological treatment, as well as the tumor biology, significantly differ between these two locations. 39 , 40 This approach is distinct from previous studies that have often generalized findings across the entire spectrum of CRC, and allows for a nuanced understanding of the impact of LNR on survival, given the different tumor biology and treatment modalities of these cancer subtypes. 41 2. MATERIALS 2.1 General Data This prospective cohort study, conducted from January 1, 2017 to June 30, 2018 across seven Polish surgical centers, enrolled 445 patients to collect survival data until September 30, 2022. Participants were 18–75 years old with primary CC or sigmoid-rectal junction cancer (C18.0-C19), eligible for radical surgery without clinical signs of metastasis. Exclusion criteria included being under 18 or over 75, refusal of surgery, treatment for another malignancy within 5 years, or previous radiotherapy, immunotherapy, or chemotherapy. All methods in this study were carried out in accordance with relevant guidelines and regulations. The experimental protocols were approved by the Bioethics Committee of the Medical University of Gdańsk (approval number NKBBN/237/2016). Written informed consent was obtained from all individual participants included in the study. 2.2 Preoperative Assessments: Data collection was carried out on the day of hospital admission before the surgical procedure. The parameters assessed included patients' age, gender, BMI, and preoperative nutritional risk, as determined by the NRS2002 score. Age was recorded in full years as an integer value. BMI was calculated using the standard formula of weight in kilograms divided by height in meters squared. The NRS2002, with a scale ranging from 0 to 7, serves as a tool to identify patients at nutritional risk. 42 , 43 Scores below 3 are indicative of no nutritional risk, whereas scores of 3 or higher signify increased risk. 2.3 Histopathological and Preoperative Evaluation The histopathological analysis included TNM staging and grading based on the AJCC 8th edition. 2 This comprehensive assessment involved the determination of lymphovascular invasion (LVI), total and metastatic lymph node counts. The LNR was calculated as the number of MLN divided by the total number of removed lymph nodes. 2.4 Surgical complications In this study, surgical complications were meticulously monitored and evaluated using the Clavien-Dindo scale, a widely recognized standard for grading surgical complications. 44 Patients were categorized into two groups based on the severity of complications. The first group included patients with no or mild complications, corresponding to Grade I and II in the Clavien-Dindo classification, encompassing non-surgical intervention cases. The second group consisted of patients with serious complications requiring surgical, endoscopic, or radiological intervention, classified as Grades III to V. This categorization facilitated a detailed comparative analysis of postoperative outcomes in relation to the severity of complications, crucial for assessing the quality of surgical care and clinical management planning. 45 2.5 Follow up Following the European Society for Medical Oncology (ESMO) guidelines for CC patients were monitored post-operatively with scheduled evaluations. 4 The primary endpoint of the study was the occurrence of all-cause death, verified through the Universal Electronic System for Registration of the Population (PESEL) national database. Changes in residence or treatment center did not affect the ability to obtain patient survival data due to the state system. Observation management was carried out independently in each participating center, allowing for robust and comprehensive data collection across different healthcare settings. Data were collected by coordinators at each center and subsequently transmitted to the central coordinating center in Gdańsk. This independent monitoring across centers aimed to provide a broad and unbiased assessment of patient outcomes post-colorectal cancer surgery. Decisions regarding the inclusion of adjuvant therapy were made individually at each center in accordance with national and ESMO guidelines. 3. METHODS 3.1. Statistical methods To account for missing values, we used multiple imputation with chained equations with 40 imputations, implemented in mice R package. 46 If missing values are not Missing Completely at Random (MCAR), then performing complete case analysis leads to bias, resulting in unreliable findings. To address this issue, multiple imputations under the assumption of Missing at Random (MAR) were used. 51 Missing values were observed in all variables included in the model except for age, sex, and disease stage. The percentage of missing values ranged from 0.5–21.5%. The association between overall survival and LNR was investigated using multivariate Cox proportional hazards model, adjusting for age, sex, BMI, LVI, disease stage, histological grading and the presence of surgical complications of grade III or higher in Clavien-Dindo scale. This approach prevents the necessity of adjusting the analysis by using multiple comparisons. These covariates have been identified as significant factors associated with survival in CC patients, as supported by previous studies. 47 – 52 We decided to include LVI in the model, to see if it is a significant factor affecting survival, after accounting for known risk factors and LNR. Kaplan-Meier curves were used to visualize the probability of survival in subgroups of patients. All analyses were conducted in R version 4.3.1. A p -value ≤ 0.05 was considered significant. 4. RESULTS 4.1 Baseline characteristics of all participants A total of 423 patients were included in the study (Table 1 ). The average BMI of participants was 28.0 ± 5.2. Regarding the number of dissected lymph nodes, in 100 patients (24.1%) a total of fewer than 12 lymph nodes were removed, while in 315 (75.9%) 12 or more were removed. Among the participants, 264 (63.8%) had no lymph node metastases, whereas 150 (36.2%) presented with metastases. LVI was observed in 123 patients (29.4%), while 296 (70.6%) did not exhibit this feature. Regarding the histological grade of the tumor, 41 patients (10.0%) were classified as G1, 318 (77.8%) as G2, and 50 (12.2%) as G3. Based on postoperative histopathological reports and considering the 8th AJCC classification, 74 patients (17.5%) were in stage I, 189 (44.7%) in stage II, and 160 (37.8%) in stage III. Table 1 Characteristics of the whole cohort. SD – standard deviation Characteristics Overall (N = 423) Age (mean ± SD) 62.42 (9.21) Sex (%) Female 210 (49.6) Male 213 (50.4) Lymph nodes ratio (mean ± SD) 0.07 (0.14) Tumor histological grade (%) G1 41 (10.0) G2 318 (77.8) G3 50 (12.2) Tumor stage (%) I 74 (17.5) II 189 (44.7) III 160 (37.8) NRS2002 score Less than 3 289 (72.1) At least 3 112 (27.9) BMI (mean ± SD) 27.97 (5.17) Number of dissected lymph nodes (%) Less than 12 100 (24.1) At least 12 315 (75.9) Lymph node metastases (%) No 264 (63.8) Yes 150 (36.2) Lymphovascular invasion (%) No 296 (70.6) Yes 123 (29.4) Surgical complications (Clavien-Dindo grade) (%) Less than grade III or no complications 390 (92.9) At least grade III 30 (7.1) Among the study participants, 70 patients (16.0%) experienced surgical complications. Complications of grade I, which are typically minor and do not require interventional treatment, occurred in 4 patients (1.0%). Complications of grade II, requiring pharmacological treatment beyond standard measures such as antibiotics, blood transfusions, or analgesics, were observed in 32 patients (7.6%). Complications of grade III, requiring interventional treatment via surgical, endoscopic, or radiologic means, occurred in 23 patients (5.5%). More severe complications of grade IV indicating serious events (e.g. organ failure), were observed in 5 patients (1.2%). The most severe complications, classified as grade V occurred in 3 patients (0.7%). The data outlined above are presented collectively in Table 1 . There were 11 missing values for the LNR data. The mean duration of observation for the whole cohort (including deaths and censored observations) is 403 days, with an interquartile range (IQR) of 1745–1975 days. For censored observations the mean duration is 1891 days, with an IQR of 1801–2002 days. 4.2 Multivariate Cox model analyses result In the multivariate Cox model, LNR, BMI and grade III or higher surgical complications were independently associated with overall survival in colon cancer patients (Table 2 ). For LNR, a 0.1-unit increase was associated with a 26% increase in the hazard of death over the whole observation period (95% CI: 7–48% increase, p = 0.006 ), holding all other factors in the model constant, underscoring its critical importance as a prognostic factor where hazard ratio is the ratio of hazard rates, and these rates are instantaneous. Table 2 Multivariate Cox model analyses identifying factors associated with the prognosis of patients with colon cancer (BMI – body mass index, CI – confidence interval, HR – hazard ratio, LNR – lymph nodes ratio) Characteristic HR 95% CI p -value Age 1.02 0.98, 1.05 0.3 Sex Male — — Female 1.23 0.74, 2.06 0.4 BMI 1.07 1.02, 1.13 0.007 Grade III Clavien-Dindo or more No — — Yes 2.25 1.06, 4.78 0.035 Lymphovascular invasion No — — Yes 1.53 0.89, 2.61 0.12 LNR (per 0.1 unit) 1.26 1.07, 1.48 0.006 Stage I — — II 1.11 0.46, 2.68 0.8 III 1.02 0.39, 2.67 > 0.9 Grading G1 — — G2 1.03 0.35, 3.03 > 0.9 G3 2.12 0.64, 7.02 0.2 BMI also emerged as a relevant factor of OS probability. For each one-unit increase in BMI, there was a 7% increase in the hazard rate of death (95% CI: 2–13% increase, p = 0.007 ). This result suggests an association between higher BMI and increased mortality in CC patients, after adjustment for known prognostic factors. The Kaplan-Meier curve (Fig. 1 ) stratified by BMI class, after excluding six underweight patients (BMI < 18.5), suggests that the survival probability of obese vs. non-obese patients diverge, and they were significantly different at least one time point (log-rank test p -value = 0.018 ; Fig. 1 ). The severity of postoperative complications, classified as grade III Clavien-Dindo or higher, significantly impacted patients’ survival. Patients with such complications had a hazard rate of death 125% higher compared to patients with complications grade II or lower (95% CI: 6–378% increase, p = 0.035 ), highlighting the need for effective management of postoperative care. After adjustment for known prognostic factors and LNR in the model, the association between LVI and OS in CC patients was not significant (HR of 1.53, 95% CI: 0.89 to 2.61, p = 0.12). This observation suggests the need for further studies to clarify its role in CC prognosis. Additionally, the analysis of cancer stages II and III, compared to stage I, did not reveal any significant differences in mortality (stage II HR: 1.11, 95% CI: 0.46 to 2.68, p = 0.8; stage III HR: 1.02, 95% CI: 0.39 to 2.67, p > 0.9), indicating that stage alone may not be a definitive predictor of survival after adjustment for LNR and other variables included in the Cox model. Kaplan-Meier curve demonstrating the survival probability in patients with stage I-III disease is shown in Fig. 2 . Our analysis revealed that even within the subset of patients with fewer than 12 lymph nodes examined, the Lymph Node Ratio (LNR) remains significantly associated with survival outcomes in CC patients. This association persists despite the small sample size and highlights the prognostic relevance of LNR in scenarios of limited lymph node retrieval. 5. DISCUSSION In this study, the main observation is the significant role of the LNR as an independent prognostic factor in predicting OS for patients with CC. In the present study 0.1-unit increase of LNR was associated with a 26% higher hazard of death (95% CI: 7–48% increase, p = 0.006 ). Significant association of LNR with survival, even in patients with fewer than 12 lymph nodes excision, underscores its potential utility as a robust prognostic marker in CC. This result emphasizes the importance of LNR, distinguishing it from other prognostic indicators used in clinical settings such as the TNM staging system. Several researchers have attempted to incorporate the LNR into the traditional staging system of CRC, focusing on the determination of specific cutoff points to enhance prognostic accuracy. Berger AC et al. demonstrated that LNR cutoffs below 5%, 5–20%, 20–40%, and above 40% significantly predict DFS and OS in stage II and III CC patients post-adjuvant treatment. 19 Wang et al. proposed categorizing LNR into four subgroups based on their ratios: less than 1/14, from 1/14 to less than 0.25, from 0.25 to less than 0.50, and from 0.50 to 1.0. 17 Sabbagh et al. identified that an LNR of 10% serves as the optimal threshold to differentiate between stage III colon cancer patients with a "good prognosis" and those with a "poor prognosis". 23 Moreover, Shinto E et al. suggested distinct LNR thresholds for assessing prognosis in stage III CC based on the tumor's location, advocating for cutoff values of 0.16 for right-sided and 0.22 for left-sided cancers. 53 A notable limitation of this investigation is the absence of specifics regarding adjuvant therapies utilized, hindering any potential for assessing or adjusting the effects of such treatments. This gap is particularly significant given that the majority of patients at stage III, as well as those identified as “high-risk” in stage II, are typically candidates for adjuvant therapy. 4 This aspect underscores the necessity for future research to incorporate data on adjuvant treatments to fully understand their impact on patient outcomes within the studied cohort. Our study does not encompass data regarding DFS. The majority of disease recurrences occur in the initial years following surgical treatment. During the COLOFOL trial, which focused on patients who had undergone high-quality surgical resection for stage II or III CRC, a significant majority (87.3%) of recurrences became apparent within the first three years after the procedure. 58 This underscores the important role of high-quality surgical treatment in managing CRC. For a surgeon, both the radicality of the surgical procedure, the extent of lymphadenectomy, and postoperative complications are of paramount importance regarding the patient's prognosis. In our study, severe postoperative complications (classified on the Clavien-Dindo grade 3 and more) occurred in 30 (7.1%) patients and had an impact on long-term survival probability (HR 2.25, CI 1.06, 4.78). Statistics also include deaths within the perioperative period up to 30 days after surgery (n = 3). In their study, Duraes LC et al. found post-surgery complications are negatively affect long-term cancer treatment results. 59 The more severe these complications are, as rated by the Clavien-Dindo scale, the worse the oncological outcomes tend to be. This suggest that reducing the occurrence and severity of these complications could lead to better outcomes for patients. Additionally, Aoyama et al. established that postoperative complications significantly affect overall and disease-free survival, regardless of adjuvant therapy or tumor site. 60 The incidence of postoperative complications classified as grade III or above observed in our research is consistent with outcomes reported in existing scientific literature. In their study, Matsuda A et al. reported a postoperative complication rate of grade III or higher at 8.1%. 61 Therefore, incorporating the severity of postoperative complications appears to be of paramount importance in designing models for future research. In this prospective, multi-center cohort study, utilizing multiple imputation and a multivariate Cox model, we have identified the LNR as an independent determinant in the prognosis of patients with CC. The application of multiple imputation in our methodological approach addresses the challenges of missing data, thus avoiding bias that would result from including only complete observations. These results highlight the significant prognostic impact of LNR, alongside BMI and postoperative complications, as key factors in patient outcomes. LNR should be considered as an essential factor in the development of future oncological staging systems. Declarations 9. COMPETING INTEREST The authors declare that they have no competing interests. 7. FUNDING This research received no specific grant from any funding agency, commercial, or not-for-profit sectors. Author Contribution M.E. conceived and designed the study, served as the principal investigator, conducted the statistical analysis, and drafted and finalized the manuscript. E.J.-S. contributed to the statistical analysis, revised the draft, and created the figures. M.U. reviewed and edited the draft and tables. M.B., A.G., B.K., M.N., M.P., and A.S. participated as researchers. D.W. contributed to the draft revisions. T.J. supervised the study, assisted in study design, and provided formal guidance. All authors reviewed and approved the final manuscript. Acknowledgement The manuscript was written during the Clinical Scholars Research Training Poland Certificate Program at Harvard Medical School Postgraduate Medical Education, which was facilitated by the Polish Medical Research Agency (ABM). Data Availability The data supporting the findings of this study were collected and analyzed by the authors. These data are not publicly available but can be provided upon reasonable request. Requests for data access should be directed to the corresponding author at [email protected] . References Wojciechowska U, Barańska K, Miklewska M, Didkowska JA. Cancer incidence and mortality in Poland in 2020. Biul Pol Tow Onkol Nowotw 2023; 8 : 167–183. Weiser MR. AJCC 8th Edition: Colorectal Cancer. Ann Surg Oncol 2018; 25 : 1454–1455. Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen Y-J, Ciombor KK et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19 : 329–359. Argilés G, Tabernero J, Labianca R, Hochhauser D, Salazar R, Iveson T et al. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol 2020; 31 : 1291–1305. Ji H, Hu C, Yang X, Liu Y, Ji G, Ge S et al. Lymph node metastasis in cancer progression: molecular mechanisms, clinical significance and therapeutic interventions. Signal Transduct Target Ther 2023; 8 : 1–33. Zhou H, Lei P, Padera TP. Progression of Metastasis through Lymphatic System. Cells 2021; 10 : 627. Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK et al. (eds.). AJCC Cancer Staging Manual . Springer International Publishing: Cham, 2017 doi:10.1007/978-3-319-40618-3. Yamashita K, Ooki A, Sakuramoto S, Kikuchi S, Katada N, Kobayashi N et al. Lymph node metastasis density (ND)-factor association with malignant degree and ND40 as ‘non-curative factor’ in gastric cancer. Anticancer Res 2008; 28 : 435–441. Zhang Q-W, Zhang C-H, Pan Y-B, Biondi A, Fico V, Persiani R et al. Prognosis of colorectal cancer patients is associated with the novel log odds of positive lymph nodes scheme: derivation and external validation. J Cancer 2020; 11 : 1702–1711. Chen SL, Steele SR, Eberhardt J, Zhu K, Bilchik A, Stojadinovic A. Lymph node ratio as a quality and prognostic indicator in stage III colon cancer. Ann Surg 2011; 253 : 82–87. Jin C, Deng X, Li Y, He W, Yang X, Liu J. Lymph node ratio is an independent prognostic factor for rectal cancer after neoadjuvant therapy: A meta-analysis. J Evid-Based Med 2018; 11 : 169–175. Riediger H, Keck T, Wellner U, zur Hausen A, Adam U, Hopt UT et al. The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J Gastrointest Surg Off J Soc Surg Aliment Tract 2009; 13 : 1337–1344. Mansour J, Sagiv D, Alon E, Talmi Y. Prognostic value of lymph node ratio in metastatic papillary thyroid carcinoma. J Laryngol Otol 2018; 132 : 8–13. Kim J, Park J, Park H, Choi MS, Jang HW, Kim TH et al. Metastatic Lymph Node Ratio for Predicting Recurrence in Medullary Thyroid Cancer. Cancers 2021; 13 : 5842. Zhou J, Lin Z, Lyu M, Chen N, Liao H, Wang Z et al. Prognostic value of lymph node ratio in non-small-cell lung cancer: a meta-analysis. Jpn J Clin Oncol 2020; 50 : 44–57. Bu DD, Ferrandino R, Robinson EM, Liu S, Miles BA, Teng MS et al. Lymph Node Ratio in HPV-Associated Oropharyngeal Cancer: Identification of a Prognostic Threshold. The Laryngoscope 2021; 131 : E184–E189. Wang J, Hassett JM, Dayton MT, Kulaylat MN. Lymph node ratio: role in the staging of node-positive colon cancer. Ann Surg Oncol 2008; 15 : 1600–1608. Ceelen W, Van Nieuwenhove Y, Pattyn P. Prognostic value of the lymph node ratio in stage III colorectal cancer: a systematic review. Ann Surg Oncol 2010; 17 : 2847–2855. Berger AC, Sigurdson ER, LeVoyer T, Hanlon A, Mayer RJ, Macdonald JS et al. Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol Off J Am Soc Clin Oncol 2005; 23 : 8706–8712. Park IJ, Choi G-S, Jun SH. Nodal stage of stage III colon cancer: the impact of metastatic lymph node ratio. J Surg Oncol 2009; 100 : 240–243. Li Destri G, Barchitta M, Pesce A, Latteri S, Bosco D, Di Cataldo A et al. Predictive Value of the Number of Harvested Lymph Nodes and Cut-Off for Lymph Node Ratio in the Prognosis of Stage II and III Colorectal Cancer Patients. J Investig Surg Off J Acad Surg Res 2019; 32 : 1–7. Shimomura M, Ikeda S, Takakura Y, Kawaguchi Y, Tokunaga M, Egi H et al. Adequate lymph node examination is essential to ensure the prognostic value of the lymph node ratio in patients with stage III colorectal cancer. Surg Today 2011; 41 : 1370–1379. Sabbagh C, Mauvais F, Cosse C, Rebibo L, Joly J-P, Dromer D et al. A lymph node ratio of 10% is predictive of survival in stage III colon cancer: a French regional study. Int Surg 2014; 99 : 344–353. Lymph Node Evaluation and Survival After Curative Resection of Colon Cancer: Systematic Review | JNCI: Journal of the National Cancer Institute | Oxford Academic. https://academic.oup.com/jnci/article/99/6/433/2522246 (accessed 27 Jan2024). Freund MR, Edden Y, Reissman P, Dagan A. Iatrogenic superior mesenteric vein injury: the perils of high ligation. Int J Colorectal Dis 2016; 31 : 1649–1651. Brouwer NPM, Hugen N, Nagtegaal ID. More extensive lymphadenectomy in colon cancer; how far are we willing to go for a biomarker? Tech Coloproctology 2020; 24 : 761–764. Bertelsen CA, Neuenschwander AU, Jansen JE, Kirkegaard-Klitbo A, Tenma JR, Wilhelmsen M et al. Short-term outcomes after complete mesocolic excision compared with ‘conventional’ colonic cancer surgery. Br J Surg 2016; 103 : 581–589. Cathomas M, Galli R, Heigl A, Lamm S, Glaser C, Cathomas G et al. Comparison of right hemicolectomies with and without complete mesocolic excision (CME). Br J Surg 2022; 109 : znac181.007. Rosenberg R, Friederichs J, Schuster T, Gertler R, Maak M, Becker K et al. Prognosis of Patients With Colorectal Cancer Is Associated With Lymph Node Ratio: A Single-Center Analysis of 3026 Patients Over a 25-Year Time Period. Ann Surg 2008; 248 : 968. Macedo F, Sequeira H, Ladeira K, Bonito N, Viana C, Martins S. Metastatic lymph node ratio as a better prognostic tool than the TNM system in colorectal cancer. Future Oncol Lond Engl 2021; 17 : 1519–1532. Peschaud F, Benoist S, Julié C, Beauchet A, Penna C, Rougier P et al. The ratio of metastatic to examined lymph nodes is a powerful independent prognostic factor in rectal cancer. Ann Surg 2008; 248 : 1067–1073. Zhang C-H, Li Y-Y, Zhang Q-W, Biondi A, Fico V, Persiani R et al. The Prognostic Impact of the Metastatic Lymph Nodes Ratio in Colorectal Cancer. Front Oncol 2018; 8 : 628. Karjol U, Jonnada P, Chandranath A, Cherukuru S. Lymph Node Ratio as a Prognostic Marker in Rectal Cancer Survival: A Systematic Review and Meta-Analysis. Cureus ; 12 : e8047. Fang HY, Yang H, He ZS, Zhao H, Fu ZM, Zhou FX et al. Log odds of positive lymph nodes is superior to the number- and ratio-based lymph node classification systems for colorectal cancer patients undergoing curative (R0) resection. Mol Clin Oncol 2017; 6 : 782–788. Li T, Yang Y, Wu W, Fu Z, Cheng F, Qiu J et al. Prognostic implications of ENE and LODDS in relation to lymph node-positive colorectal cancer location. Transl Oncol 2021; 14 : 101190. Occhionorelli S, Andreotti D, Vallese P, Morganti L, Lacavalla D, Forini E et al. Evaluation on prognostic efficacy of lymph nodes ratio (LNR) and log odds of positive lymph nodes (LODDS) in complicated colon cancer: the first study in emergency surgery. World J Surg Oncol 2018; 16 : 186. Xu T, Zhang L, Yu L, Zhu Y, Fang H, Chen B et al. Log odds of positive lymph nodes is an excellent prognostic factor for patients with rectal cancer after neoadjuvant chemoradiotherapy. Ann Transl Med 2021; 9 : 637. Arrichiello G, Pirozzi M, Facchini BA, Facchini S, Paragliola F, Nacca V et al. Beyond N staging in colorectal cancer: Current approaches and future perspectives. Front Oncol 2022; 12 . doi:10.3389/fonc.2022.937114. Baqar AR, Wilkins S, Wang W, Oliva K, McMurrick P. Log odds of positive lymph nodes is prognostically equivalent to lymph node ratio in non-metastatic colon cancer. BMC Cancer 2020; 20 : 762. Jiang C, Wang F, Guo G, Dong J, Liu S, He W et al. Metastatic lymph node ratio as a prognostic indicator in patients with stage IV colon cancer undergoing resection. J Cancer 2019; 10 : 2534–2540. Ahmad A, Reha J, Saied A, Espat NJ, Somasundar P, Katz SC. Association of primary tumor lymph node ratio with burden of liver metastases and survival in stage IV colorectal cancer. Hepatobiliary Surg Nutr 2017; 6 : 154–161. Deng Y, Peng J, Zhao Y, Sui Q, Zhao R, Lu Z et al. Lymph node ratio as a valuable prognostic factor for patients with colorectal liver-only metastasis undergoing curative resection. Cancer Manag Res 2018; 10 : 2083–2094. Tamas K, Walenkamp AME, de Vries EGE, van Vugt M a. TM, Beets-Tan RG, van Etten B et al. Rectal and colon cancer: Not just a different anatomic site. Cancer Treat Rev 2015; 41 : 671–679. Differences in management and outcome for colon and rectal carcinoma with synchronous liver metastases: a population‐based cohort study - Båverud Olsson - 2021 - Colorectal Disease - Wiley Online Library. https://onlinelibrary.wiley.com/doi/full/10.1111/codi.15468 (accessed 27 Jan2024). Yang Y, Wang Y, Wang Z. Construction of a new clinical staging system for colorectal cancer based on the lymph node ratio: A validation study. Front Surg 2022; 9 : 929576. Kondrup J, Allison SP, Elia M, Vellas B, Plauth M, Educational and Clinical Practice Committee, European Society of Parenteral and Enteral Nutrition (ESPEN). ESPEN guidelines for nutrition screening 2002. Clin Nutr Edinb Scotl 2003; 22 : 415–421. Muscaritoli M, Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H et al. ESPEN practical guideline: Clinical Nutrition in cancer. Clin Nutr 2021; 40 : 2898–2913. Dindo D. The Clavien–Dindo Classification of Surgical Complications. In: Cuesta MA, Bonjer HJ (eds). Treatment of Postoperative Complications After Digestive Surgery . Springer: London, 2014, pp 13–17. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD et al. The Clavien-Dindo Classification of Surgical Complications: Five-Year Experience. Ann Surg 2009; 250 : 187–196. Buuren S van, Groothuis-Oudshoorn K. mice: Multivariate Imputation by Chained Equations in R. J Stat Softw 2011; 45 : 1–67. van Buuren S. Multiple imputation of discrete and continuous data by fully conditional specification. Stat Methods Med Res 2007; 16 : 219–242. Steele SR, Park GE, Johnson EK, Martin MJ, Stojadinovic A, Maykel JA et al. The impact of age on colorectal cancer incidence, treatment, and outcomes in an equal-access health care system. Dis Colon Rectum 2014; 57 : 303–310. Yang Y, Wang G, He J, Ren S, Wu F, Zhang J et al. Gender differences in colorectal cancer survival: A meta-analysis. Int J Cancer 2017; 141 : 1942–1949. Samawi HH, Yin Y, Speers CH, Cheung WY. Sex Disparities in Outcomes of Early Stage Colorectal Cancer: A Population-Based Study. Clin Colorectal Cancer 2018; 17 : e711–e717. Hu C, Zhang Q, Jin X, Zhang L, Zhang Y, Zhu Q et al. A paradox between preoperative overweight/obesity and change in weight during postoperative chemotherapy and its relationship to survival in stage Ⅱ and Ⅲ colorectal cancer patients. Clin Nutr Edinb Scotl 2021; 40 : 2410–2419. Basile D, Rosati G, Bergamo F, Garattini SK, Banzi M, Zampino M et al. Prognostic Value of Body Mass Index in Stage II/III Colon Cancer: Posthoc Analysis From the TOSCA Trial. Clin Colorectal Cancer 2023; 22 : 190–198. Ulanja MB, Rishi M, Beutler BD, Sharma M, Patterson DR, Gullapalli N et al. Colon Cancer Sidedness, Presentation, and Survival at Different Stages. J Oncol 2019; 2019 : 4315032. Shinto E, Ike H, Hida J, Kobayashi H, Hashiguchi Y, Kajiwara Y et al. Marked impact of tumor location on the appropriate cutoff values and the prognostic significance of the lymph node ratio in stage III colon cancer: a multi-institutional retrospective analysis. J Gastroenterol 2019; 54 : 597–607. Hansdotter P, Scherman P, Petersen SH, Mikalonis M, Holmberg E, Rizell M et al. Patterns and resectability of colorectal cancer recurrences: outcome study within the COLOFOL trial. BJS Open 2021; 5 : zrab067. Duraes LC, Stocchi L, Steele SR, Kalady MF, Church JM, Gorgun E et al. The Relationship Between Clavien-Dindo Morbidity Classification and Oncologic Outcomes After Colorectal Cancer Resection. Ann Surg Oncol 2018; 25 : 188–196. Aoyama T, Oba K, Honda M, Sadahiro S, Hamada C, Mayanagi S et al. Impact of postoperative complications on the colorectal cancer survival and recurrence: analyses of pooled individual patients’ data from three large phase III randomized trials. Cancer Med 2017; 6 : 1573–1580. Matsuda A, Maruyama H, Akagi S, Inoue T, Uemura K, Kobayashi M et al. Do postoperative infectious complications really affect long-term survival in colorectal cancer surgery? A multicenter retrospective cohort study. Ann Gastroenterol Surg 2023; 7 : 110–120. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Apr, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 12 Jan, 2026 Reviews received at journal 05 Jan, 2026 Reviewers agreed at journal 23 Dec, 2025 Reviews received at journal 06 Oct, 2025 Reviewers agreed at journal 26 Sep, 2025 Reviewers agreed at journal 28 Aug, 2025 Reviewers agreed at journal 20 Jul, 2025 Reviewers invited by journal 18 Jul, 2025 Editor assigned by journal 17 Jul, 2025 Editor invited by journal 14 Apr, 2025 Submission checks completed at journal 11 Apr, 2025 First submitted to journal 05 Apr, 2025 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-6383521","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":488052111,"identity":"0bb4c3bc-7a33-45a2-8845-f73b4934b35e","order_by":0,"name":"Marcin Ekman","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYFAC5gMgkrGBgcEASFsQo4UtAVmLBDFaeAxI1MLPnvP5NW+OjWwDe/M2CcYdRGiR7Hm7zZp3W5pxA8+xMgnGM0RoMbiRu82Yd9vhxAaJHDMJxjYitNjfyHkG1PI/sUH+DZFaDCRymB/zbjsAtIWHSC0SZ56ZMc7dlmzcxpNWbJFIjF/425Mff3i7zU62n/3wxhsfd9gQ1sLAkMAGNpkNRCQ2EKODIYH5A5zNSJyWUTAKRsEoGGEAAHUlNnhD27/oAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Surgical Oncology, Transplant Surgery and General Surgery, Medical University of Gdansk","correspondingAuthor":true,"prefix":"","firstName":"Marcin","middleName":"","lastName":"Ekman","suffix":""},{"id":488052112,"identity":"bdfdb77c-6ca7-445a-b2cf-8467bb3d6198","order_by":1,"name":"Elzbieta Jodłowska-Siewert","email":"","orcid":"","institution":"Division of Biostatistic, University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Elzbieta","middleName":"","lastName":"Jodłowska-Siewert","suffix":""},{"id":488052115,"identity":"ffc4363e-2aee-4810-82cc-a26c1a43a286","order_by":2,"name":"Marcin Urbanowicz","email":"","orcid":"","institution":"1Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Marcin","middleName":"","lastName":"Urbanowicz","suffix":""},{"id":488052116,"identity":"05c0b94b-b529-4078-aa58-63b78001c008","order_by":3,"name":"Maciej Berut","email":"","orcid":"","institution":"Department of General Surgery with Subdivision of Oncological Surgery, District Health Center in Brzeziny","correspondingAuthor":false,"prefix":"","firstName":"Maciej","middleName":"","lastName":"Berut","suffix":""},{"id":488052117,"identity":"8a78e8c1-f25c-479c-a2bc-1c052927c427","order_by":4,"name":"Alan Grabowski","email":"","orcid":"","institution":"Department of Surgery, Clinic of Surgical Oncology and Neuroendocrine Tumors, Maria Sklodowska-Curie National Research Institute of Oncology","correspondingAuthor":false,"prefix":"","firstName":"Alan","middleName":"","lastName":"Grabowski","suffix":""},{"id":488052118,"identity":"124b9591-0127-4458-8a5b-44d4cade063b","order_by":5,"name":"Bartosz Kapturkiewicz","email":"","orcid":"","institution":"First Department of Oncological Surgery of Lower Silesian Oncology Center","correspondingAuthor":false,"prefix":"","firstName":"Bartosz","middleName":"","lastName":"Kapturkiewicz","suffix":""},{"id":488052119,"identity":"4771f26e-1d84-46e5-833f-bbc15fb9e324","order_by":6,"name":"Michał Nycz","email":"","orcid":"","institution":"Department of General, Colorectal and Polytrauma Surgery, Faculty of Health Sciences in Katowice, Medical University of Silesia","correspondingAuthor":false,"prefix":"","firstName":"Michał","middleName":"","lastName":"Nycz","suffix":""},{"id":488052120,"identity":"548e333b-1662-4a48-9c38-cb4e21c7dd3e","order_by":7,"name":"Michał Putko","email":"","orcid":"","institution":"Department of General and Gastrointestinal Surgery and Nutrition, Copernicus Hospital Gdansk","correspondingAuthor":false,"prefix":"","firstName":"Michał","middleName":"","lastName":"Putko","suffix":""},{"id":488052121,"identity":"2c17b8e5-2407-458e-a5c1-4dd3ff30b9b7","order_by":8,"name":"Arkadiusz Szarmach","email":"","orcid":"","institution":"Szpital Specjalistyczny w Kościerzynie Sp. z o.o.","correspondingAuthor":false,"prefix":"","firstName":"Arkadiusz","middleName":"","lastName":"Szarmach","suffix":""},{"id":488052122,"identity":"2cc17903-6185-4873-a782-2e226d1a9b05","order_by":9,"name":"Dudzic Wojciech","email":"","orcid":"","institution":"Department of General and Gastrointestinal Surgery and Nutrition, Copernicus Hospital Gdansk","correspondingAuthor":false,"prefix":"","firstName":"Dudzic","middleName":"","lastName":"Wojciech","suffix":""},{"id":488052123,"identity":"629c3f1c-195d-4e61-8269-ae82c7b6bb12","order_by":10,"name":"Tomasz Jastrzębski","email":"","orcid":"","institution":"Division of Gynecology and Obstetrics, Medical University of Gdansk","correspondingAuthor":false,"prefix":"","firstName":"Tomasz","middleName":"","lastName":"Jastrzębski","suffix":""}],"badges":[],"createdAt":"2025-04-05 18:38:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6383521/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6383521/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-026-50360-1","type":"published","date":"2026-04-27T15:57:23+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87384406,"identity":"cea75776-9436-49c8-a966-b2abb73e4851","added_by":"auto","created_at":"2025-07-23 08:49:29","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":219738,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curves for patients divided into groups based on BMI categories (n = 326) excluding 6 underweight patients (point estimates with 95% confidence intervals).\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6383521/v1/3de72d02a7373c04242e5c26.jpeg"},{"id":87386424,"identity":"048e2a34-3a36-4e8c-b22e-5c205874407e","added_by":"auto","created_at":"2025-07-23 08:57:29","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":236478,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier Survival Curve Demonstrating the Impact of stage on Overall Survival in Patients with Colon Cancer.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6383521/v1/1af36428eebfde73ef554cda.jpeg"},{"id":108437944,"identity":"17971840-a50c-4fb7-92c3-5673f61ca54d","added_by":"auto","created_at":"2026-05-04 16:04:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":877861,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6383521/v1/75105b90-a4c1-4d64-84fd-e5b79f8d255d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"What is the impact of the Lymph Node Ratio (LNR) on Overall Survival (OS) in patients with colon cancer?","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eColorectal cancer (CRC) remains a significant global health challenge and a leading cause of cancer-related mortality.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Among prognostic tools, the TNM (Tumor, Node, Metastasis) classification system, updated to its 8th edition by the American Joint Committee on Cancer (AJCC), stands as the cornerstone for assessing the clinical stage of this disease.\u003csup\u003e\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Metastasis to lymph nodes is a key mechanism in the process of cancer spread.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e In the AJCC 8th edition TNM classification for colon cancer (CC), the N category is defined by the number of identified metastatic lymph nodes (MLN).\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e While effective in long-term outcome prediction, the TNM system is acknowledged for its limited consideration of critical MLN aspects. Due to its limitations and simplifications, this system does not account for, among other factors, the total number of removed lymph nodes. In the 8th edition of the AJCC Cancer Staging Manual, the Lymph Node Ratio (LNR) in colon cancer prognosis is emphasized as a key additional factor for further evaluation, highlighting its growing significance in prognostic assessments.\u003c/p\u003e\u003cp\u003eLNR, defined as the ratio of pathologically positive lymph nodes to the total number of examined nodes, is considered a significant prognostic factor in various malignancies, including breast, pancreatic, thyroid, esophageal, gastric, oropharyngeal, non-small-cell lung, and colorectal cancer.\u003csup\u003e\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e In these cancers, a high LNR has been significantly correlated with poorer prognosis for patients, indicating its potential as a marker for more intensive treatment and more aggressive post-therapy follow-up.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e The investigation into the relationship between LNR and survival in stage III colon cancer patients was initially undertaken by Wang J. et al. using data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e The study found that a higher lymph node ratio (LNR) is associated with poorer survival outcomes in node-positive CC patients and offers superior prognostic information compared to traditional pN staging. Furthermore, the prognostic significance of LNR is particularly notable when fewer than 12 lymph nodes are examined, emphasizing the need for adequate lymph node assessment during surgery. \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e An undeniable limitation of this study was its retrospective nature.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Ceelen et al. provided a valuable contribution to the understanding of prognostic factors in CC and CRC through their meta-analysis of 16 studies involving patients with these malignancies. This analysis confirmed that the utilization of LNR as a predictive factor allows better differentiation of this type of cancer compared to the N stage. Furthermore, the cumulative Hazard Ratio (HR) analysis revealed LNR as a significant prognostic factor for overall survival (OS) and for disease-free survival (DFS).\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e The review by Ceelen et al. highlights limitations such as the retrospective nature of included studies and methodological variability, which may impact the findings on the prognostic value of the LNR in stage III CRC. Various authors have debated the utility of the LNR in the context of the minimum number of sampled lymph nodes for analysis.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e In numerous studies, it has been emphasized that an adequate examination of lymph nodes (\u0026gt;\u0026thinsp;12) is crucial to maintain the prognostic significance of LNR in stage III colorectal cancer patients.\u003csup\u003e\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Current guidelines also specify a minimum of 12 lymph nodes in colon cancer surgery to minimize the false-negative rate of lymph node metastasis and to prevent under-staging.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e This suggests that the extent of lymphadenectomy plays a significant role in patient outcomes, with a higher number of lymph nodes removed being associated with better long-term survival.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e However, the procedure is not without risks, as expanding lymphadenectomy could lead to complications such as damage to the superior mesenteric vein (SMV), intraoperative bleeding, lymph leakage, sexual dysfunction, and damage to internal organs, with some studies suggesting these risks may not translate into long-term survival benefits.\u003csup\u003e\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Given these concerns, the routine performance of Complete Mesocolic Excision (CME) with high vascular ligation, as advocated by some for all colon cancer patients, has been contested.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn contrast to previous studies, the above-mentioned authors suggested that LNR has a superior prognostic value compared to the pN category, irrespective of the minimum number of lymph nodes examined.\u003csup\u003e\u003cspan additionalcitationids=\"CR30 CR31\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e Furthermore, Macedo et al. emphasize that LNR demonstrates enhanced prognostic utility, particularly in the subgroup of patients with lymphadenectomy extent lower than recommended in the guidelines.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Also these studies were retrospective and were limited to colon or rectal III stage cancer.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe potential impact of LNR has been observed across different stages of CC, implying its prognostic significance for both early and advanced disease presentations. Fang et. al indicated that the LNR accurately predicts the prognosis of patients with early-stage CC.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e Li et al., in a study encompassing 389 eligible patients with CRC in stages I-IV, demonstrated that LNR is an independent prognostic factor. However, it is essential to note that this study was limited by its single-center retrospective design.\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e The LNR has been confirmed additionally as an independent prognostic factor in stage IV CC with liver-only metastasis undergoing curative resection.\u003csup\u003e\u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eInterestingly, recent years have seen a growing interest in investigating the log odds of positive lymph nodes (LODDS) as a new prognostic factor.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan additionalcitationids=\"CR55\" citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e This metric, essentially a mathematical transformation of the LNR, has been explored for its prognostic significance in CC. Beqar et al. demonstrated that the prognostic impact of LODDS is comparable to that of LNR for CC patients, suggesting it does not provide new insights beyond what LNR already offers.\u003csup\u003e\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e Furthermore, the simplicity and ease of calculation argue in favor of using LNR as a straightforward, effective prognostic tool in clinical practice.\u003c/p\u003e\u003cp\u003eThe aim of this research is a prospective view on LNR as a potential prognostic marker, even though it is not currently recognized in the AJCC 8th edition TNM classification. Due to the limited understanding of LNR's clinical significance in these specific contexts, our multi-center prospective research involves a comprehensive analysis of clinical data. A crucial aspect of our analysis includes utilizing a multivariate Cox proportional hazards model to explore the relationship between overall survival and LNR, incorporating a broad spectrum of influencing factors. Unlike other studies, the model presented in this study also considers surgically relevant aspects such as the patient's Body Mass Index (BMI) and the severity of postoperative complications as classified by the Clavien-Dindo scale.\u003c/p\u003e\u003cp\u003eOur research is focusing on patients diagnosed with CC (stage I-III). Although both colon and rectal cancers are classified under CRC, the surgical and oncological treatment, as well as the tumor biology, significantly differ between these two locations.\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e This approach is distinct from previous studies that have often generalized findings across the entire spectrum of CRC, and allows for a nuanced understanding of the impact of LNR on survival, given the different tumor biology and treatment modalities of these cancer subtypes.\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e"},{"header":"2. MATERIALS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 General Data\u003c/h2\u003e\u003cp\u003eThis prospective cohort study, conducted from January 1, 2017 to June 30, 2018 across seven Polish surgical centers, enrolled 445 patients to collect survival data until September 30, 2022. Participants were 18\u0026ndash;75 years old with primary CC or sigmoid-rectal junction cancer (C18.0-C19), eligible for radical surgery without clinical signs of metastasis. Exclusion criteria included being under 18 or over 75, refusal of surgery, treatment for another malignancy within 5 years, or previous radiotherapy, immunotherapy, or chemotherapy. All methods in this study were carried out in accordance with relevant guidelines and regulations. The experimental protocols were approved by the Bioethics Committee of the Medical University of Gdańsk (approval number NKBBN/237/2016). Written informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Preoperative Assessments:\u003c/h2\u003e\u003cp\u003eData collection was carried out on the day of hospital admission before the surgical procedure. The parameters assessed included patients' age, gender, BMI, and preoperative nutritional risk, as determined by the NRS2002 score. Age was recorded in full years as an integer value. BMI was calculated using the standard formula of weight in kilograms divided by height in meters squared. The NRS2002, with a scale ranging from 0 to 7, serves as a tool to identify patients at nutritional risk.\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e Scores below 3 are indicative of no nutritional risk, whereas scores of 3 or higher signify increased risk.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Histopathological and Preoperative Evaluation\u003c/h2\u003e\u003cp\u003eThe histopathological analysis included TNM staging and grading based on the AJCC 8th edition.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e This comprehensive assessment involved the determination of lymphovascular invasion (LVI), total and metastatic lymph node counts. The LNR was calculated as the number of MLN divided by the total number of removed lymph nodes.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Surgical complications\u003c/h2\u003e\u003cp\u003eIn this study, surgical complications were meticulously monitored and evaluated using the Clavien-Dindo scale, a widely recognized standard for grading surgical complications.\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e Patients were categorized into two groups based on the severity of complications. The first group included patients with no or mild complications, corresponding to Grade I and II in the Clavien-Dindo classification, encompassing non-surgical intervention cases. The second group consisted of patients with serious complications requiring surgical, endoscopic, or radiological intervention, classified as Grades III to V. This categorization facilitated a detailed comparative analysis of postoperative outcomes in relation to the severity of complications, crucial for assessing the quality of surgical care and clinical management planning.\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Follow up\u003c/h2\u003e\u003cp\u003eFollowing the European Society for Medical Oncology (ESMO) guidelines for CC patients were monitored post-operatively with scheduled evaluations.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e The primary endpoint of the study was the occurrence of all-cause death, verified through the Universal Electronic System for Registration of the Population (PESEL) national database. Changes in residence or treatment center did not affect the ability to obtain patient survival data due to the state system. Observation management was carried out independently in each participating center, allowing for robust and comprehensive data collection across different healthcare settings. Data were collected by coordinators at each center and subsequently transmitted to the central coordinating center in Gdańsk. This independent monitoring across centers aimed to provide a broad and unbiased assessment of patient outcomes post-colorectal cancer surgery. Decisions regarding the inclusion of adjuvant therapy were made individually at each center in accordance with national and ESMO guidelines.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. METHODS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Statistical methods\u003c/h2\u003e\u003cp\u003eTo account for missing values, we used multiple imputation with chained equations with 40 imputations, implemented in mice R package.\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e If missing values are not Missing Completely at Random (MCAR), then performing complete case analysis leads to bias, resulting in unreliable findings. To address this issue, multiple imputations under the assumption of Missing at Random (MAR) were used.\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e Missing values were observed in all variables included in the model except for age, sex, and disease stage. The percentage of missing values ranged from 0.5\u0026ndash;21.5%. The association between overall survival and LNR was investigated using multivariate Cox proportional hazards model, adjusting for age, sex, BMI, LVI, disease stage, histological grading and the presence of surgical complications of grade III or higher in Clavien-Dindo scale. This approach prevents the necessity of adjusting the analysis by using multiple comparisons. These covariates have been identified as significant factors associated with survival in CC patients, as supported by previous studies.\u003csup\u003e\u003cspan additionalcitationids=\"CR48 CR49 CR50 CR51\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e We decided to include LVI in the model, to see if it is a significant factor affecting survival, after accounting for known risk factors and LNR. Kaplan-Meier curves were used to visualize the probability of survival in subgroups of patients. All analyses were conducted in R version 4.3.1. A \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026le;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"4. RESULTS","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e4.1 Baseline characteristics of all participants\u003c/h2\u003e\u003cp\u003eA total of 423 patients were included in the study (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The average BMI of participants was 28.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2. Regarding the number of dissected lymph nodes, in 100 patients (24.1%) a total of fewer than 12 lymph nodes were removed, while in 315 (75.9%) 12 or more were removed. Among the participants, 264 (63.8%) had no lymph node metastases, whereas 150 (36.2%) presented with metastases. LVI was observed in 123 patients (29.4%), while 296 (70.6%) did not exhibit this feature. Regarding the histological grade of the tumor, 41 patients (10.0%) were classified as G1, 318 (77.8%) as G2, and 50 (12.2%) as G3. Based on postoperative histopathological reports and considering the 8th AJCC classification, 74 patients (17.5%) were in stage I, 189 (44.7%) in stage II, and 160 (37.8%) in stage III.\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\u003eCharacteristics of the whole cohort. SD \u0026ndash; standard deviation\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOverall\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;423)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e62.42 (9.21)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e210 (49.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e213 (50.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymph nodes ratio (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.07 (0.14)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor histological grade (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eG1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e41 (10.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eG2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e318 (77.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eG3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e50 (12.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor stage (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e74 (17.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e189 (44.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e160 (37.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNRS2002 score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLess than 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e289 (72.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt least 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e112 (27.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e27.97 (5.17)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of dissected lymph nodes (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLess than 12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e100 (24.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt least 12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e315 (75.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymph node metastases (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e264 (63.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e150 (36.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymphovascular invasion (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e296 (70.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e123 (29.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurgical complications (Clavien-Dindo grade) (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLess than grade III or no complications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e390 (92.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt least grade III\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e30 (7.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAmong the study participants, 70 patients (16.0%) experienced surgical complications. Complications of grade I, which are typically minor and do not require interventional treatment, occurred in 4 patients (1.0%). Complications of grade II, requiring pharmacological treatment beyond standard measures such as antibiotics, blood transfusions, or analgesics, were observed in 32 patients (7.6%). Complications of grade III, requiring interventional treatment via surgical, endoscopic, or radiologic means, occurred in 23 patients (5.5%). More severe complications of grade IV indicating serious events (e.g. organ failure), were observed in 5 patients (1.2%). The most severe complications, classified as grade V occurred in 3 patients (0.7%). The data outlined above are presented collectively in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There were 11 missing values for the LNR data.\u003c/p\u003e\u003cp\u003eThe mean duration of observation for the whole cohort (including deaths and censored observations) is 403 days, with an interquartile range (IQR) of 1745\u0026ndash;1975 days. For censored observations the mean duration is 1891 days, with an IQR of 1801\u0026ndash;2002 days.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e4.2 Multivariate Cox model analyses result\u003c/h2\u003e\u003cp\u003eIn the multivariate Cox model, LNR, BMI and grade III or higher surgical complications were independently associated with overall survival in colon cancer patients (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). For LNR, a 0.1-unit increase was associated with a 26% increase in the hazard of death over the whole observation period (95% CI: 7\u0026ndash;48% increase, \u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;0.006\u003c/b\u003e), holding all other factors in the model constant, underscoring its critical importance as a prognostic factor where hazard ratio is the ratio of hazard rates, and these rates are instantaneous.\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\u003eMultivariate Cox model analyses identifying factors associated with the prognosis of patients with colon cancer (BMI \u0026ndash; body mass index, CI \u0026ndash; confidence interval, HR \u0026ndash; hazard ratio, LNR \u0026ndash; lymph nodes ratio)\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\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\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.98, 1.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.74, 2.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.02, 1.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGrade III Clavien-Dindo or more\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.06, 4.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.035\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymphovascular invasion\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.89, 2.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLNR\u003c/b\u003e (per 0.1 unit)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.07, 1.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.46, 2.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.39, 2.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGrading\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eG1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eG2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.35, 3.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eG3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.64, 7.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.2\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\u003eBMI also emerged as a relevant factor of OS probability. For each one-unit increase in BMI, there was a 7% increase in the hazard rate of death (95% CI: 2\u0026ndash;13% increase, \u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;0.007\u003c/b\u003e). This result suggests an association between higher BMI and increased mortality in CC patients, after adjustment for known prognostic factors. The Kaplan-Meier curve (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) stratified by BMI class, after excluding six underweight patients (BMI\u0026thinsp;\u0026lt;\u0026thinsp;18.5), suggests that the survival probability of obese vs. non-obese patients diverge, and they were significantly different at least one time point (log-rank test \u003cb\u003ep\u003c/b\u003e\u003cb\u003e-value\u0026thinsp;=\u0026thinsp;0.018\u003c/b\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe severity of postoperative complications, classified as grade III Clavien-Dindo or higher, significantly impacted patients\u0026rsquo; survival. Patients with such complications had a hazard rate of death 125% higher compared to patients with complications grade II or lower (95% CI: 6\u0026ndash;378% increase, \u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;0.035\u003c/b\u003e), highlighting the need for effective management of postoperative care.\u003c/p\u003e\u003cp\u003eAfter adjustment for known prognostic factors and LNR in the model, the association between LVI and OS in CC patients was not significant (HR of 1.53, 95% CI: 0.89 to 2.61, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.12). This observation suggests the need for further studies to clarify its role in CC prognosis.\u003c/p\u003e\u003cp\u003eAdditionally, the analysis of cancer stages II and III, compared to stage I, did not reveal any significant differences in mortality (stage II HR: 1.11, 95% CI: 0.46 to 2.68, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.8; stage III HR: 1.02, 95% CI: 0.39 to 2.67, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.9), indicating that stage alone may not be a definitive predictor of survival after adjustment for LNR and other variables included in the Cox model. Kaplan-Meier curve demonstrating the survival probability in patients with stage I-III disease is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eOur analysis revealed that even within the subset of patients with fewer than 12 lymph nodes examined, the Lymph Node Ratio (LNR) remains significantly associated with survival outcomes in CC patients. This association persists despite the small sample size and highlights the prognostic relevance of LNR in scenarios of limited lymph node retrieval.\u003c/p\u003e\u003c/div\u003e"},{"header":"5. DISCUSSION","content":"\u003cp\u003eIn this study, the main observation is the significant role of the LNR as an independent prognostic factor in predicting OS for patients with CC. In the present study 0.1-unit increase of LNR was associated with a 26% higher hazard of death (95% CI: 7\u0026ndash;48% increase, \u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;0.006\u003c/b\u003e). Significant association of LNR with survival, even in patients with fewer than 12 lymph nodes excision, underscores its potential utility as a robust prognostic marker in CC. This result emphasizes the importance of LNR, distinguishing it from other prognostic indicators used in clinical settings such as the TNM staging system. Several researchers have attempted to incorporate the LNR into the traditional staging system of CRC, focusing on the determination of specific cutoff points to enhance prognostic accuracy. Berger AC et al. demonstrated that LNR cutoffs below 5%, 5\u0026ndash;20%, 20\u0026ndash;40%, and above 40% significantly predict DFS and OS in stage II and III CC patients post-adjuvant treatment.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Wang et al. proposed categorizing LNR into four subgroups based on their ratios: less than 1/14, from 1/14 to less than 0.25, from 0.25 to less than 0.50, and from 0.50 to 1.0.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Sabbagh et al. identified that an LNR of 10% serves as the optimal threshold to differentiate between stage III colon cancer patients with a \"good prognosis\" and those with a \"poor prognosis\".\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Moreover, Shinto E et al. suggested distinct LNR thresholds for assessing prognosis in stage III CC based on the tumor's location, advocating for cutoff values of 0.16 for right-sided and 0.22 for left-sided cancers.\u003csup\u003e\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eA notable limitation of this investigation is the absence of specifics regarding adjuvant therapies utilized, hindering any potential for assessing or adjusting the effects of such treatments. This gap is particularly significant given that the majority of patients at stage III, as well as those identified as \u0026ldquo;high-risk\u0026rdquo; in stage II, are typically candidates for adjuvant therapy.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e This aspect underscores the necessity for future research to incorporate data on adjuvant treatments to fully understand their impact on patient outcomes within the studied cohort.\u003c/p\u003e\u003cp\u003eOur study does not encompass data regarding DFS. The majority of disease recurrences occur in the initial years following surgical treatment. During the COLOFOL trial, which focused on patients who had undergone high-quality surgical resection for stage II or III CRC, a significant majority (87.3%) of recurrences became apparent within the first three years after the procedure.\u003csup\u003e\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u003c/sup\u003e This underscores the important role of high-quality surgical treatment in managing CRC. For a surgeon, both the radicality of the surgical procedure, the extent of lymphadenectomy, and postoperative complications are of paramount importance regarding the patient's prognosis. In our study, severe postoperative complications (classified on the Clavien-Dindo grade 3 and more) occurred in 30 (7.1%) patients and had an impact on long-term survival probability (HR 2.25, CI 1.06, 4.78). Statistics also include deaths within the perioperative period up to 30 days after surgery (n\u0026thinsp;=\u0026thinsp;3). In their study, Duraes LC et al. found post-surgery complications are negatively affect long-term cancer treatment results.\u003csup\u003e\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e\u003c/sup\u003e The more severe these complications are, as rated by the Clavien-Dindo scale, the worse the oncological outcomes tend to be. This suggest that reducing the occurrence and severity of these complications could lead to better outcomes for patients. Additionally, Aoyama et al. established that postoperative complications significantly affect overall and disease-free survival, regardless of adjuvant therapy or tumor site.\u003csup\u003e\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e The incidence of postoperative complications classified as grade III or above observed in our research is consistent with outcomes reported in existing scientific literature. In their study, Matsuda A et al. reported a postoperative complication rate of grade III or higher at 8.1%.\u003csup\u003e61\u003c/sup\u003e Therefore, incorporating the severity of postoperative complications appears to be of paramount importance in designing models for future research.\u003c/p\u003e\u003cp\u003eIn this prospective, multi-center cohort study, utilizing multiple imputation and a multivariate Cox model, we have identified the LNR as an independent determinant in the prognosis of patients with CC. The application of multiple imputation in our methodological approach addresses the challenges of missing data, thus avoiding bias that would result from including only complete observations. These results highlight the significant prognostic impact of LNR, alongside BMI and postoperative complications, as key factors in patient outcomes. LNR should be considered as an essential factor in the development of future oncological staging systems.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003e9. COMPETING INTEREST\u003c/h2\u003e\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003e7. FUNDING\u003c/h2\u003e\u003cp\u003eThis research received no specific grant from any funding agency, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.E. conceived and designed the study, served as the principal investigator, conducted the statistical analysis, and drafted and finalized the manuscript. E.J.-S. contributed to the statistical analysis, revised the draft, and created the figures. M.U. reviewed and edited the draft and tables. M.B., A.G., B.K., M.N., M.P., and A.S. participated as researchers. D.W. contributed to the draft revisions. T.J. supervised the study, assisted in study design, and provided formal guidance. All authors reviewed and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe manuscript was written during the Clinical Scholars Research Training Poland Certificate Program at Harvard Medical School Postgraduate Medical Education, which was facilitated by the Polish Medical Research Agency (ABM).\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the findings of this study were collected and analyzed by the authors. These data are not publicly available but can be provided upon reasonable request. Requests for data access should be directed to the corresponding author at [email protected].\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWojciechowska U, Barańska K, Miklewska M, Didkowska JA. Cancer incidence and mortality in Poland in 2020. \u003cem\u003eBiul Pol Tow Onkol Nowotw\u003c/em\u003e 2023; \u003cstrong\u003e8\u003c/strong\u003e: 167\u0026ndash;183.\u003c/li\u003e\n\u003cli\u003eWeiser MR. AJCC 8th Edition: Colorectal Cancer. \u003cem\u003eAnn Surg Oncol\u003c/em\u003e 2018; \u003cstrong\u003e25\u003c/strong\u003e: 1454\u0026ndash;1455.\u003c/li\u003e\n\u003cli\u003eBenson AB, Venook AP, Al-Hawary MM, Arain MA, Chen Y-J, Ciombor KK \u003cem\u003eet al.\u003c/em\u003e Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. \u003cem\u003eJ Natl Compr Canc Netw\u003c/em\u003e 2021; \u003cstrong\u003e19\u003c/strong\u003e: 329\u0026ndash;359.\u003c/li\u003e\n\u003cli\u003eArgil\u0026eacute;s G, Tabernero J, Labianca R, Hochhauser D, Salazar R, Iveson T \u003cem\u003eet al.\u003c/em\u003e Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. \u003cem\u003eAnn Oncol Off J Eur Soc Med Oncol\u003c/em\u003e 2020; \u003cstrong\u003e31\u003c/strong\u003e: 1291\u0026ndash;1305.\u003c/li\u003e\n\u003cli\u003eJi H, Hu C, Yang X, Liu Y, Ji G, Ge S \u003cem\u003eet al.\u003c/em\u003e Lymph node metastasis in cancer progression: molecular mechanisms, clinical significance and therapeutic interventions. \u003cem\u003eSignal Transduct Target Ther\u003c/em\u003e 2023; \u003cstrong\u003e8\u003c/strong\u003e: 1\u0026ndash;33.\u003c/li\u003e\n\u003cli\u003eZhou H, Lei P, Padera TP. Progression of Metastasis through Lymphatic System. \u003cem\u003eCells\u003c/em\u003e 2021; \u003cstrong\u003e10\u003c/strong\u003e: 627.\u003c/li\u003e\n\u003cli\u003eAmin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK \u003cem\u003eet al.\u003c/em\u003e (eds.). \u003cem\u003eAJCC Cancer Staging Manual\u003c/em\u003e. Springer International Publishing: Cham, 2017 doi:10.1007/978-3-319-40618-3.\u003c/li\u003e\n\u003cli\u003eYamashita K, Ooki A, Sakuramoto S, Kikuchi S, Katada N, Kobayashi N \u003cem\u003eet al.\u003c/em\u003e Lymph node metastasis density (ND)-factor association with malignant degree and ND40 as \u0026lsquo;non-curative factor\u0026rsquo; in gastric cancer. \u003cem\u003eAnticancer Res\u003c/em\u003e 2008; \u003cstrong\u003e28\u003c/strong\u003e: 435\u0026ndash;441.\u003c/li\u003e\n\u003cli\u003eZhang Q-W, Zhang C-H, Pan Y-B, Biondi A, Fico V, Persiani R \u003cem\u003eet al.\u003c/em\u003e Prognosis of colorectal cancer patients is associated with the novel log odds of positive lymph nodes scheme: derivation and external validation. \u003cem\u003eJ Cancer\u003c/em\u003e 2020; \u003cstrong\u003e11\u003c/strong\u003e: 1702\u0026ndash;1711.\u003c/li\u003e\n\u003cli\u003eChen SL, Steele SR, Eberhardt J, Zhu K, Bilchik A, Stojadinovic A. Lymph node ratio as a quality and prognostic indicator in stage III colon cancer. \u003cem\u003eAnn Surg\u003c/em\u003e 2011; \u003cstrong\u003e253\u003c/strong\u003e: 82\u0026ndash;87.\u003c/li\u003e\n\u003cli\u003eJin C, Deng X, Li Y, He W, Yang X, Liu J. Lymph node ratio is an independent prognostic factor for rectal cancer after neoadjuvant therapy: A meta-analysis. \u003cem\u003eJ Evid-Based Med\u003c/em\u003e 2018; \u003cstrong\u003e11\u003c/strong\u003e: 169\u0026ndash;175.\u003c/li\u003e\n\u003cli\u003eRiediger H, Keck T, Wellner U, zur Hausen A, Adam U, Hopt UT \u003cem\u003eet al.\u003c/em\u003e The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. \u003cem\u003eJ Gastrointest Surg Off J Soc Surg Aliment Tract\u003c/em\u003e 2009; \u003cstrong\u003e13\u003c/strong\u003e: 1337\u0026ndash;1344.\u003c/li\u003e\n\u003cli\u003eMansour J, Sagiv D, Alon E, Talmi Y. Prognostic value of lymph node ratio in metastatic papillary thyroid carcinoma. \u003cem\u003eJ Laryngol Otol\u003c/em\u003e 2018; \u003cstrong\u003e132\u003c/strong\u003e: 8\u0026ndash;13.\u003c/li\u003e\n\u003cli\u003eKim J, Park J, Park H, Choi MS, Jang HW, Kim TH \u003cem\u003eet al.\u003c/em\u003e Metastatic Lymph Node Ratio for Predicting Recurrence in Medullary Thyroid Cancer. \u003cem\u003eCancers\u003c/em\u003e 2021; \u003cstrong\u003e13\u003c/strong\u003e: 5842.\u003c/li\u003e\n\u003cli\u003eZhou J, Lin Z, Lyu M, Chen N, Liao H, Wang Z \u003cem\u003eet al.\u003c/em\u003e Prognostic value of lymph node ratio in non-small-cell lung cancer: a meta-analysis. \u003cem\u003eJpn J Clin Oncol\u003c/em\u003e 2020; \u003cstrong\u003e50\u003c/strong\u003e: 44\u0026ndash;57.\u003c/li\u003e\n\u003cli\u003eBu DD, Ferrandino R, Robinson EM, Liu S, Miles BA, Teng MS \u003cem\u003eet al.\u003c/em\u003e Lymph Node Ratio in HPV-Associated Oropharyngeal Cancer: Identification of a Prognostic Threshold. \u003cem\u003eThe Laryngoscope\u003c/em\u003e 2021; \u003cstrong\u003e131\u003c/strong\u003e: E184\u0026ndash;E189.\u003c/li\u003e\n\u003cli\u003eWang J, Hassett JM, Dayton MT, Kulaylat MN. Lymph node ratio: role in the staging of node-positive colon cancer. \u003cem\u003eAnn Surg Oncol\u003c/em\u003e 2008; \u003cstrong\u003e15\u003c/strong\u003e: 1600\u0026ndash;1608.\u003c/li\u003e\n\u003cli\u003eCeelen W, Van Nieuwenhove Y, Pattyn P. Prognostic value of the lymph node ratio in stage III colorectal cancer: a systematic review. \u003cem\u003eAnn Surg Oncol\u003c/em\u003e 2010; \u003cstrong\u003e17\u003c/strong\u003e: 2847\u0026ndash;2855.\u003c/li\u003e\n\u003cli\u003eBerger AC, Sigurdson ER, LeVoyer T, Hanlon A, Mayer RJ, Macdonald JS \u003cem\u003eet al.\u003c/em\u003e Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. \u003cem\u003eJ Clin Oncol Off J Am Soc Clin Oncol\u003c/em\u003e 2005; \u003cstrong\u003e23\u003c/strong\u003e: 8706\u0026ndash;8712.\u003c/li\u003e\n\u003cli\u003ePark IJ, Choi G-S, Jun SH. Nodal stage of stage III colon cancer: the impact of metastatic lymph node ratio. \u003cem\u003eJ Surg Oncol\u003c/em\u003e 2009; \u003cstrong\u003e100\u003c/strong\u003e: 240\u0026ndash;243.\u003c/li\u003e\n\u003cli\u003eLi Destri G, Barchitta M, Pesce A, Latteri S, Bosco D, Di Cataldo A \u003cem\u003eet al.\u003c/em\u003e Predictive Value of the Number of Harvested Lymph Nodes and Cut-Off for Lymph Node Ratio in the Prognosis of Stage II and III Colorectal Cancer Patients. \u003cem\u003eJ Investig Surg Off J Acad Surg Res\u003c/em\u003e 2019; \u003cstrong\u003e32\u003c/strong\u003e: 1\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eShimomura M, Ikeda S, Takakura Y, Kawaguchi Y, Tokunaga M, Egi H \u003cem\u003eet al.\u003c/em\u003e Adequate lymph node examination is essential to ensure the prognostic value of the lymph node ratio in patients with stage III colorectal cancer. \u003cem\u003eSurg Today\u003c/em\u003e 2011; \u003cstrong\u003e41\u003c/strong\u003e: 1370\u0026ndash;1379.\u003c/li\u003e\n\u003cli\u003eSabbagh C, Mauvais F, Cosse C, Rebibo L, Joly J-P, Dromer D \u003cem\u003eet al.\u003c/em\u003e A lymph node ratio of 10% is predictive of survival in stage III colon cancer: a French regional study. \u003cem\u003eInt Surg\u003c/em\u003e 2014; \u003cstrong\u003e99\u003c/strong\u003e: 344\u0026ndash;353.\u003c/li\u003e\n\u003cli\u003eLymph Node Evaluation and Survival After Curative Resection of Colon Cancer: Systematic Review | JNCI: Journal of the National Cancer Institute | Oxford Academic. https://academic.oup.com/jnci/article/99/6/433/2522246 (accessed 27 Jan2024).\u003c/li\u003e\n\u003cli\u003eFreund MR, Edden Y, Reissman P, Dagan A. Iatrogenic superior mesenteric vein injury: the perils of high ligation. \u003cem\u003eInt J Colorectal Dis\u003c/em\u003e 2016; \u003cstrong\u003e31\u003c/strong\u003e: 1649\u0026ndash;1651.\u003c/li\u003e\n\u003cli\u003eBrouwer NPM, Hugen N, Nagtegaal ID. More extensive lymphadenectomy in colon cancer; how far are we willing to go for a biomarker? \u003cem\u003eTech Coloproctology\u003c/em\u003e 2020; \u003cstrong\u003e24\u003c/strong\u003e: 761\u0026ndash;764.\u003c/li\u003e\n\u003cli\u003eBertelsen CA, Neuenschwander AU, Jansen JE, Kirkegaard-Klitbo A, Tenma JR, Wilhelmsen M \u003cem\u003eet al.\u003c/em\u003e Short-term outcomes after complete mesocolic excision compared with \u0026lsquo;conventional\u0026rsquo; colonic cancer surgery. \u003cem\u003eBr J Surg\u003c/em\u003e 2016; \u003cstrong\u003e103\u003c/strong\u003e: 581\u0026ndash;589.\u003c/li\u003e\n\u003cli\u003eCathomas M, Galli R, Heigl A, Lamm S, Glaser C, Cathomas G \u003cem\u003eet al.\u003c/em\u003e Comparison of right hemicolectomies with and without complete mesocolic excision (CME). \u003cem\u003eBr J Surg\u003c/em\u003e 2022; \u003cstrong\u003e109\u003c/strong\u003e: znac181.007.\u003c/li\u003e\n\u003cli\u003eRosenberg R, Friederichs J, Schuster T, Gertler R, Maak M, Becker K \u003cem\u003eet al.\u003c/em\u003e Prognosis of Patients With Colorectal Cancer Is Associated With Lymph Node Ratio: A Single-Center Analysis of 3026 Patients Over a 25-Year Time Period. \u003cem\u003eAnn Surg\u003c/em\u003e 2008; \u003cstrong\u003e248\u003c/strong\u003e: 968.\u003c/li\u003e\n\u003cli\u003eMacedo F, Sequeira H, Ladeira K, Bonito N, Viana C, Martins S. Metastatic lymph node ratio as a better prognostic tool than the TNM system in colorectal cancer. \u003cem\u003eFuture Oncol Lond Engl\u003c/em\u003e 2021; \u003cstrong\u003e17\u003c/strong\u003e: 1519\u0026ndash;1532.\u003c/li\u003e\n\u003cli\u003ePeschaud F, Benoist S, Juli\u0026eacute; C, Beauchet A, Penna C, Rougier P \u003cem\u003eet al.\u003c/em\u003e The ratio of metastatic to examined lymph nodes is a powerful independent prognostic factor in rectal cancer. \u003cem\u003eAnn Surg\u003c/em\u003e 2008; \u003cstrong\u003e248\u003c/strong\u003e: 1067\u0026ndash;1073.\u003c/li\u003e\n\u003cli\u003eZhang C-H, Li Y-Y, Zhang Q-W, Biondi A, Fico V, Persiani R \u003cem\u003eet al.\u003c/em\u003e The Prognostic Impact of the Metastatic Lymph Nodes Ratio in Colorectal Cancer. \u003cem\u003eFront Oncol\u003c/em\u003e 2018; \u003cstrong\u003e8\u003c/strong\u003e: 628.\u003c/li\u003e\n\u003cli\u003eKarjol U, Jonnada P, Chandranath A, Cherukuru S. Lymph Node Ratio as a Prognostic Marker in Rectal Cancer Survival: A Systematic Review and Meta-Analysis. \u003cem\u003eCureus\u003c/em\u003e; \u003cstrong\u003e12\u003c/strong\u003e: e8047.\u003c/li\u003e\n\u003cli\u003eFang HY, Yang H, He ZS, Zhao H, Fu ZM, Zhou FX \u003cem\u003eet al.\u003c/em\u003e Log odds of positive lymph nodes is superior to the number- and ratio-based lymph node classification systems for colorectal cancer patients undergoing curative (R0) resection. \u003cem\u003eMol Clin Oncol\u003c/em\u003e 2017; \u003cstrong\u003e6\u003c/strong\u003e: 782\u0026ndash;788.\u003c/li\u003e\n\u003cli\u003eLi T, Yang Y, Wu W, Fu Z, Cheng F, Qiu J \u003cem\u003eet al.\u003c/em\u003e Prognostic implications of ENE and LODDS in relation to lymph node-positive colorectal cancer location. \u003cem\u003eTransl Oncol\u003c/em\u003e 2021; \u003cstrong\u003e14\u003c/strong\u003e: 101190.\u003c/li\u003e\n\u003cli\u003eOcchionorelli S, Andreotti D, Vallese P, Morganti L, Lacavalla D, Forini E \u003cem\u003eet al.\u003c/em\u003e Evaluation on prognostic efficacy of lymph nodes ratio (LNR) and log odds of positive lymph nodes (LODDS) in complicated colon cancer: the first study in emergency surgery. \u003cem\u003eWorld J Surg Oncol\u003c/em\u003e 2018; \u003cstrong\u003e16\u003c/strong\u003e: 186.\u003c/li\u003e\n\u003cli\u003eXu T, Zhang L, Yu L, Zhu Y, Fang H, Chen B \u003cem\u003eet al.\u003c/em\u003e Log odds of positive lymph nodes is an excellent prognostic factor for patients with rectal cancer after neoadjuvant chemoradiotherapy. \u003cem\u003eAnn Transl Med\u003c/em\u003e 2021; \u003cstrong\u003e9\u003c/strong\u003e: 637.\u003c/li\u003e\n\u003cli\u003eArrichiello G, Pirozzi M, Facchini BA, Facchini S, Paragliola F, Nacca V \u003cem\u003eet al.\u003c/em\u003e Beyond N staging in colorectal cancer: Current approaches and future perspectives. \u003cem\u003eFront Oncol\u003c/em\u003e 2022; \u003cstrong\u003e12\u003c/strong\u003e. doi:10.3389/fonc.2022.937114.\u003c/li\u003e\n\u003cli\u003eBaqar AR, Wilkins S, Wang W, Oliva K, McMurrick P. Log odds of positive lymph nodes is prognostically equivalent to lymph node ratio in non-metastatic colon cancer. \u003cem\u003eBMC Cancer\u003c/em\u003e 2020; \u003cstrong\u003e20\u003c/strong\u003e: 762.\u003c/li\u003e\n\u003cli\u003eJiang C, Wang F, Guo G, Dong J, Liu S, He W \u003cem\u003eet al.\u003c/em\u003e Metastatic lymph node ratio as a prognostic indicator in patients with stage IV colon cancer undergoing resection. \u003cem\u003eJ Cancer\u003c/em\u003e 2019; \u003cstrong\u003e10\u003c/strong\u003e: 2534\u0026ndash;2540.\u003c/li\u003e\n\u003cli\u003eAhmad A, Reha J, Saied A, Espat NJ, Somasundar P, Katz SC. Association of primary tumor lymph node ratio with burden of liver metastases and survival in stage IV colorectal cancer. \u003cem\u003eHepatobiliary Surg Nutr\u003c/em\u003e 2017; \u003cstrong\u003e6\u003c/strong\u003e: 154\u0026ndash;161.\u003c/li\u003e\n\u003cli\u003eDeng Y, Peng J, Zhao Y, Sui Q, Zhao R, Lu Z \u003cem\u003eet al.\u003c/em\u003e Lymph node ratio as a valuable prognostic factor for patients with colorectal liver-only metastasis undergoing curative resection. \u003cem\u003eCancer Manag Res\u003c/em\u003e 2018; \u003cstrong\u003e10\u003c/strong\u003e: 2083\u0026ndash;2094.\u003c/li\u003e\n\u003cli\u003eTamas K, Walenkamp AME, de Vries EGE, van Vugt M a. TM, Beets-Tan RG, van Etten B \u003cem\u003eet al.\u003c/em\u003e Rectal and colon cancer: Not just a different anatomic site. \u003cem\u003eCancer Treat Rev\u003c/em\u003e 2015; \u003cstrong\u003e41\u003c/strong\u003e: 671\u0026ndash;679.\u003c/li\u003e\n\u003cli\u003eDifferences in management and outcome for colon and rectal carcinoma with synchronous liver metastases: a population‐based cohort study - B\u0026aring;verud Olsson - 2021 - Colorectal Disease - Wiley Online Library. https://onlinelibrary.wiley.com/doi/full/10.1111/codi.15468 (accessed 27 Jan2024).\u003c/li\u003e\n\u003cli\u003eYang Y, Wang Y, Wang Z. Construction of a new clinical staging system for colorectal cancer based on the lymph node ratio: A validation study. \u003cem\u003eFront Surg\u003c/em\u003e 2022; \u003cstrong\u003e9\u003c/strong\u003e: 929576.\u003c/li\u003e\n\u003cli\u003eKondrup J, Allison SP, Elia M, Vellas B, Plauth M, Educational and Clinical Practice Committee, European Society of Parenteral and Enteral Nutrition (ESPEN). ESPEN guidelines for nutrition screening 2002. \u003cem\u003eClin Nutr Edinb Scotl\u003c/em\u003e 2003; \u003cstrong\u003e22\u003c/strong\u003e: 415\u0026ndash;421.\u003c/li\u003e\n\u003cli\u003eMuscaritoli M, Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H \u003cem\u003eet al.\u003c/em\u003e ESPEN practical guideline: Clinical Nutrition in cancer. \u003cem\u003eClin Nutr\u003c/em\u003e 2021; \u003cstrong\u003e40\u003c/strong\u003e: 2898\u0026ndash;2913.\u003c/li\u003e\n\u003cli\u003eDindo D. The Clavien\u0026ndash;Dindo Classification of Surgical Complications. In: Cuesta MA, Bonjer HJ (eds). \u003cem\u003eTreatment of Postoperative Complications After Digestive Surgery\u003c/em\u003e. Springer: London, 2014, pp 13\u0026ndash;17.\u003c/li\u003e\n\u003cli\u003eClavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD \u003cem\u003eet al.\u003c/em\u003e The Clavien-Dindo Classification of Surgical Complications: Five-Year Experience. \u003cem\u003eAnn Surg\u003c/em\u003e 2009; \u003cstrong\u003e250\u003c/strong\u003e: 187\u0026ndash;196.\u003c/li\u003e\n\u003cli\u003eBuuren S van, Groothuis-Oudshoorn K. mice: Multivariate Imputation by Chained Equations in R. \u003cem\u003eJ Stat Softw\u003c/em\u003e 2011; \u003cstrong\u003e45\u003c/strong\u003e: 1\u0026ndash;67.\u003c/li\u003e\n\u003cli\u003evan Buuren S. Multiple imputation of discrete and continuous data by fully conditional specification. \u003cem\u003eStat Methods Med Res\u003c/em\u003e 2007; \u003cstrong\u003e16\u003c/strong\u003e: 219\u0026ndash;242.\u003c/li\u003e\n\u003cli\u003eSteele SR, Park GE, Johnson EK, Martin MJ, Stojadinovic A, Maykel JA \u003cem\u003eet al.\u003c/em\u003e The impact of age on colorectal cancer incidence, treatment, and outcomes in an equal-access health care system. \u003cem\u003eDis Colon Rectum\u003c/em\u003e 2014; \u003cstrong\u003e57\u003c/strong\u003e: 303\u0026ndash;310.\u003c/li\u003e\n\u003cli\u003eYang Y, Wang G, He J, Ren S, Wu F, Zhang J \u003cem\u003eet al.\u003c/em\u003e Gender differences in colorectal cancer survival: A meta-analysis. \u003cem\u003eInt J Cancer\u003c/em\u003e 2017; \u003cstrong\u003e141\u003c/strong\u003e: 1942\u0026ndash;1949.\u003c/li\u003e\n\u003cli\u003eSamawi HH, Yin Y, Speers CH, Cheung WY. Sex Disparities in Outcomes of Early Stage Colorectal Cancer: A Population-Based Study. \u003cem\u003eClin Colorectal Cancer\u003c/em\u003e 2018; \u003cstrong\u003e17\u003c/strong\u003e: e711\u0026ndash;e717.\u003c/li\u003e\n\u003cli\u003eHu C, Zhang Q, Jin X, Zhang L, Zhang Y, Zhu Q \u003cem\u003eet al.\u003c/em\u003e A paradox between preoperative overweight/obesity and change in weight during postoperative chemotherapy and its relationship to survival in stage Ⅱ and Ⅲ colorectal cancer patients. \u003cem\u003eClin Nutr Edinb Scotl\u003c/em\u003e 2021; \u003cstrong\u003e40\u003c/strong\u003e: 2410\u0026ndash;2419.\u003c/li\u003e\n\u003cli\u003eBasile D, Rosati G, Bergamo F, Garattini SK, Banzi M, Zampino M \u003cem\u003eet al.\u003c/em\u003e Prognostic Value of Body Mass Index in Stage II/III Colon Cancer: Posthoc Analysis From the TOSCA Trial. \u003cem\u003eClin Colorectal Cancer\u003c/em\u003e 2023; \u003cstrong\u003e22\u003c/strong\u003e: 190\u0026ndash;198.\u003c/li\u003e\n\u003cli\u003eUlanja MB, Rishi M, Beutler BD, Sharma M, Patterson DR, Gullapalli N \u003cem\u003eet al.\u003c/em\u003e Colon Cancer Sidedness, Presentation, and Survival at Different Stages. \u003cem\u003eJ Oncol\u003c/em\u003e 2019; \u003cstrong\u003e2019\u003c/strong\u003e: 4315032.\u003c/li\u003e\n\u003cli\u003eShinto E, Ike H, Hida J, Kobayashi H, Hashiguchi Y, Kajiwara Y \u003cem\u003eet al.\u003c/em\u003e Marked impact of tumor location on the appropriate cutoff values and the prognostic significance of the lymph node ratio in stage III colon cancer: a multi-institutional retrospective analysis. \u003cem\u003eJ Gastroenterol\u003c/em\u003e 2019; \u003cstrong\u003e54\u003c/strong\u003e: 597\u0026ndash;607.\u003c/li\u003e\n\u003cli\u003eHansdotter P, Scherman P, Petersen SH, Mikalonis M, Holmberg E, Rizell M \u003cem\u003eet al.\u003c/em\u003e Patterns and resectability of colorectal cancer recurrences: outcome study within the COLOFOL trial. \u003cem\u003eBJS Open\u003c/em\u003e 2021; \u003cstrong\u003e5\u003c/strong\u003e: zrab067.\u003c/li\u003e\n\u003cli\u003eDuraes LC, Stocchi L, Steele SR, Kalady MF, Church JM, Gorgun E \u003cem\u003eet al.\u003c/em\u003e The Relationship Between Clavien-Dindo Morbidity Classification and Oncologic Outcomes After Colorectal Cancer Resection. \u003cem\u003eAnn Surg Oncol\u003c/em\u003e 2018; \u003cstrong\u003e25\u003c/strong\u003e: 188\u0026ndash;196.\u003c/li\u003e\n\u003cli\u003eAoyama T, Oba K, Honda M, Sadahiro S, Hamada C, Mayanagi S \u003cem\u003eet al.\u003c/em\u003e Impact of postoperative complications on the colorectal cancer survival and recurrence: analyses of pooled individual patients\u0026rsquo; data from three large phase III randomized trials. \u003cem\u003eCancer Med\u003c/em\u003e 2017; \u003cstrong\u003e6\u003c/strong\u003e: 1573\u0026ndash;1580.\u003c/li\u003e\n\u003cli\u003eMatsuda A, Maruyama H, Akagi S, Inoue T, Uemura K, Kobayashi M \u003cem\u003eet al.\u003c/em\u003e Do postoperative infectious complications really affect long-term survival in colorectal cancer surgery? A multicenter retrospective cohort study. \u003cem\u003eAnn Gastroenterol Surg\u003c/em\u003e 2023; \u003cstrong\u003e7\u003c/strong\u003e: 110\u0026ndash;120.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6383521/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6383521/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e\u003cp\u003eColorectal cancer (CRC) is a major health concern globally, with lymph node metastasis being a key factor in its spread. The Lymph Node Ratio (LNR) \u0026ndash; the ratio of pathologically positive lymph nodes to the total number of examined nodes \u0026ndash; has emerged as a significant prognostic factor in CRC. Notably, there is a lack of data from prospective cohort studies on this topic. This study aims to investigate the impact of LNR on Overall Survival (OS) in patients with colon cancer, expanding the knowledge on its prognostic value beyond current AJCC TNM classification.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e\u003cp\u003eA prospective cohort study was conducted across seven Polish surgical centers enrolling 445 patients with primary colon cancer. The study collected survival data until September 30, 2022, focusing on patients aged 18\u0026ndash;75 years eligible for radical surgery. Preoperative assessments included demographic information, Body Mass Index (BMI) and histopathological evaluation according to AJCC 8th edition. Surgical complications were graded using the Clavien-Dindo scale. The relationship between OS and LNR was analyzed using a multivariate Cox proportional hazards model, adjusting for significant covariates.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eIn the multivariate Cox model, LNR, BMI and grade III or higher surgical complications were independently associated with overall survival in colon cancer patients. For LNR, a 0.1-unit increase was associated with a 26% increase in the hazard of death over the whole observation period (95% CI: 7\u0026ndash;48% increase, \u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;0.006\u003c/b\u003e).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eLNR, along with BMI and the severity of postoperative complications, serves as an independent prognostic factor for OS in colon cancer patients. These results of prospective cohort study support the inclusion of LNR in future oncological staging systems and highlight the importance of comprehensive lymph node analysis in managing colon cancer.\u003c/p\u003e","manuscriptTitle":"What is the impact of the Lymph Node Ratio (LNR) on Overall Survival (OS) in patients with colon cancer?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-23 08:49:24","doi":"10.21203/rs.3.rs-6383521/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-12T19:38:08+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-05T21:59:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"278695270105313128662957304925270804679","date":"2025-12-23T16:37:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-06T11:21:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"192816026903745801736188781566927006395","date":"2025-09-26T16:24:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"234762028117500255670787061669683119955","date":"2025-08-28T12:50:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"211228451482213589455289923818782407264","date":"2025-07-20T12:05:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-18T11:01:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-18T02:56:03+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-14T14:02:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-12T01:39:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-04-05T18:26:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"791f0851-516c-47f6-a4d6-1a14df28666f","owner":[],"postedDate":"July 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":51808311,"name":"Health sciences/Gastroenterology/Gastrointestinal diseases/Gastrointestinal cancer"},{"id":51808313,"name":"Health sciences/Oncology/Surgical oncology"}],"tags":[],"updatedAt":"2026-05-04T16:03:55+00:00","versionOfRecord":{"articleIdentity":"rs-6383521","link":"https://doi.org/10.1038/s41598-026-50360-1","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-04-27 15:57:23","publishedOnDateReadable":"April 27th, 2026"},"versionCreatedAt":"2025-07-23 08:49:24","video":"","vorDoi":"10.1038/s41598-026-50360-1","vorDoiUrl":"https://doi.org/10.1038/s41598-026-50360-1","workflowStages":[]},"version":"v1","identity":"rs-6383521","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6383521","identity":"rs-6383521","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}