Prognostic Impact of Preoperative SARC-F Score on Cancer-Specific Survival in Patients with Colorectal Cancer

Prognostic Impact of Preoperative SARC-F Score on Cancer-Specific Survival in Patients with Colorectal 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 Research Article Prognostic Impact of Preoperative SARC-F Score on Cancer-Specific Survival in Patients with Colorectal Cancer Dain Shin, Sung Uk Bae, Woon Kyung Jeong, Seong Kyu Baek This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8510816/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Sarcopenia adversely affects outcomes in patients with colorectal cancer (CRC); however, the prognostic significance of functional sarcopenia screening tools such as the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls (SARC-F) questionnaire remains unclear. Objective This study aimed to evaluate the prognostic impact of preoperative SARC-F scores on oncologic outcomes in patients with CRC. Methods We retrospectively analyzed 219 patients who underwent curative resection for CRC and completed the SARC-F questionnaire preoperatively between July 2019 and June 2021. Patients with a SARC-F score ≥ 4 were classified into the high SARC-F group. Results Of the 219 patients, 26 (11.9%) had high SARC-F scores. Compared with the low SARC-F group, patients with high SARC-F scores were older, more frequently female, had lower body mass index, a higher prevalence of diabetes mellitus, more right-sided tumors, and elevated preoperative C-reactive protein and neutrophil-to-lymphocyte ratio levels (all p < 0.05). Pathologic characteristics were comparable between groups, except for a higher number of retrieved lymph nodes in the high SARC-F group ( p = 0.033). Overall survival and cancer-specific survival were significantly lower in the high SARC-F group (OS: 82.9% vs. 92.0%, p = 0.036; CSS: 88.5% vs. 96.9%, p = 0.011), whereas disease-free survival did not differ significantly. In multivariate analysis, a SARC-F score ≥ 4 independently predicted poorer cancer-specific survival ( p = 0.032), while higher body mass index was associated with improved overall survival, and left-sided tumor location and lymphovascular invasion were independent predictors of disease-free survival. Conclusions A high preoperative SARC-F score is independently associated with inferior cancer-specific survival in patients with CRC, highlighting the prognostic relevance of functional impairment. The SARC-F questionnaire may serve as a simple and clinically feasible tool for preoperative risk stratification in colorectal cancer. Colorectal Neoplasms Sarcopenia Frailty Prognosis Survival Analysis Inflammation Figures Figure 1 Figure 2 INTRODUCTION Colorectal cancer (CRC) remains a major global health burden and has recently become the second leading cause of cancer-related mortality in both men and women, with its incidence continuing to rise worldwide [1, 2]. Despite substantial advances in surgical techniques, systemic therapy, and perioperative management, long-term outcomes after curative resection remain heterogeneous. Traditionally, prognostic stratification in CRC has relied primarily on tumor-related factors, including depth of invasion, lymph node involvement, number of examined lymph nodes, serum carcinoembryonic antigen (CEA) levels, and the presence of bowel perforation [3-5]. However, these parameters do not fully capture the wide variability in survival observed among patients with similar pathological stages. Increasing evidence suggests that host-related factors play a critical role in determining oncologic outcomes in CRC. Patient-specific characteristics such as genetic background, immune and inflammatory status, nutritional reserve, body composition, and cancer-associated cachexia have been shown to significantly influence postoperative recovery, treatment tolerance, and long-term survival [6-11]. These observations underscore a growing recognition that CRC prognosis reflects not only tumor biology but also the patient’s physiological and functional resilience. Accordingly, the identification of prognostic tools that integrate host vulnerability into routine clinical assessment has become an important component of contemporary precision oncology. Sarcopenia, defined as a progressive and systemic skeletal muscle disorder characterized by declines in muscle mass, strength, and physical performance, has emerged as a particularly relevant host-related factor in oncology [12-14]. In patients with CRC and other solid malignancies, sarcopenia has been consistently associated with increased postoperative complications, reduced tolerance to chemotherapy, and inferior survival outcomes [15-23]. Most previous studies have assessed sarcopenia using radiologic measurements of skeletal muscle mass derived from computed tomography (CT) imaging. While informative, these approaches require specialized software, standardized imaging protocols, and technical expertise, which may limit their routine applicability in daily clinical practice. Moreover, muscle mass alone may not fully reflect functional impairment, which is increasingly recognized as a critical determinant of clinical outcomes. To address these limitations, the European Working Group on Sarcopenia in Older People (EWGSOP2) recommends the use of the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls (SARC-F) questionnaire as an initial screening tool for sarcopenia[12]. The SARC-F is a simple, self-reported instrument that assesses functional decline across five domains of daily activity. Although its sensitivity for detecting low muscle mass is modest, the SARC-F demonstrates high specificity and has been shown to reliably identify individuals at risk for adverse functional and clinical outcomes[24-26]. Importantly, recent studies suggest that the SARC-F score may capture a broader concept of functional and inflammatory vulnerability, rather than muscle quantity alone, thereby providing complementary prognostic information beyond radiologic sarcopenia. Emerging evidence has linked high SARC-F scores to unfavorable outcomes in several malignancies, including urologic and gastrointestinal cancers [27, 28]. In patients undergoing colorectal cancer surgery, a high preoperative SARC-F score has been associated with increased postoperative morbidity[29]. However, despite the growing interest in functional assessment tools, the prognostic significance of the SARC-F score for long-term oncologic outcomes in colorectal cancer, particularly cancer-specific survival, has not been systematically evaluated in a homogeneous CRC cohort. Whether a simple preoperative functional assessment can independently predict oncologic prognosis beyond established clinicopathologic factors remains unclear. Therefore, the present study aimed to investigate the prognostic impact of the preoperative SARC-F score on oncologic outcomes in patients undergoing curative resection for colorectal cancer. We hypothesized that a high SARC-F score, reflecting impaired functional reserve and host vulnerability, would be independently associated with inferior cancer-specific survival, thereby providing a clinically feasible tool for preoperative risk stratification in colorectal cancer. METHODS 1. Ethical considerations This study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of Keimyung University Dongsan Medical Center (IRB No. 2022-12-040). Given the retrospective nature of the study and the use of anonymized clinical data, the requirement for written informed consent was waived. 2. Study population We retrospectively reviewed consecutive patients who underwent curative resection for colorectal cancer between July 2019 and June 2021 at Keimyung University Dongsan Medical Center, Daegu, Korea. All patients were of Asian ethnicity. To ensure cohort homogeneity and minimize confounding, patients were excluded if they met any of the following criteria: presence of synchronous or prior malignancies, histologic subtypes other than adenocarcinoma, diagnosis of familial adenomatous polyposis or Lynch syndrome, incomplete preoperative blood cell count data, or failure to complete the preoperative SARC-F questionnaire. Among 351 patients initially screened, 132 were excluded based on these criteria. The final study cohort consisted of 219 patients, who were subsequently stratified into two groups according to their preoperative SARC-F score: a high SARC-F group (score ≥4) and a low SARC-F group (score <4). Restricting the analysis to patients who completed the SARC-F questionnaire was intended to reduce clinical heterogeneity and allow consistent functional assessment across the cohort. 3. Data collection and definitions Clinical, laboratory, and pathologic data were obtained from prospectively maintained institutional databases and electronic medical records. Baseline variables included age, sex, body mass index (BMI), comorbidities (hypertension and diabetes mellitus), tumor location, American Society of Anesthesiologists (ASA) physical status classification, and preoperative laboratory parameters, including carcinoembryonic antigen (CEA), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR). The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count obtained from preoperative blood tests. Pathologic variables included T stage, N stage, M stage, histologic differentiation, tumor size, number of retrieved and positive lymph nodes, lymphovascular invasion (LVI), perineural invasion (PNI), tumor budding, and microsatellite instability (MSI) status. Tumors were staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. MSI status was assessed using polymerase chain reaction (PCR) amplification of five microsatellite markers recommended by the National Cancer Institute (BAT25, BAT26, D5S346, D2S123, and D17S250). Tumors were classified as MSI-high if instability was detected in two or more markers, MSI-low if instability was detected in one marker, and microsatellite stable if no instability was detected. 4. SARC-F assessment The SARC-F questionnaire was administered preoperatively at the time of hospital admission. The questionnaire consists of five self-reported items assessing strength, assistance with walking, ability to rise from a chair, ability to climb stairs, and history of falls. Each item is scored from 0 to 2, yielding a total score ranging from 0 to 10. Consistent with established recommendations, a total score of ≥4 was used to define a high SARC-F score, indicative of impaired functional status and probable sarcopenia. 5. Oncologic outcomes and definitions Overall survival (OS) was defined as the interval from the date of surgery to death from any cause or last follow-up. Disease-free survival (DFS) was defined as the time from surgery to the first documented recurrence or last follow-up, with recurrence confirmed radiologically or histologically. Cancer-specific survival (CSS) was defined as the time from surgery to death attributable to colorectal cancer. Local recurrence was defined as tumor recurrence within the surgical field, whereas recurrence accompanied by distant metastasis was classified as systemic recurrence. 6. Statistical analysis Continuous variables were expressed as means with standard deviations, and categorical variables were presented as frequencies with percentages. The normality of continuous variables was assessed using the Shapiro–Wilk test. Comparisons between groups were performed using the independent t-test or Mann–Whitney U test for continuous variables, as appropriate, and the chi-square test or Fisher’s exact test for categorical variables. Survival outcomes were analyzed using the Kaplan–Meier method and compared using the log-rank test. Cox proportional hazards regression models were used to identify prognostic factors for OS, DFS, and CSS. Variables with a p-value <0.10 in univariate analyses were entered into multivariate models to reduce the risk of overfitting. Given the limited number of events in the high SARC-F group, multivariate analyses were considered exploratory in nature. The proportional hazards assumption was evaluated using Schoenfeld residuals. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. Based on prior literature, cutoff values for CEA and CRP were set at 5.0 ng/mL and 1.0 mg/L, respectively. A two-sided p-value <0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics version 27 (IBM Corp., Armonk, NY, USA). RESULTS 1. Baseline Characteristics of patients Among the 219 patients included in the analysis, 193 (88.1%) had a low SARC-F score (<4), whereas 26 patients (11.9%) were classified into the high SARC-F group (score ≥4) (Figure 1). Baseline characteristics according to SARC-F status are summarized in Table 1. Patients with high SARC-F scores were significantly older and more likely to be female compared with those with low scores (76.5 ± 7.9 vs. 64.8 ± 11.6 years, p < 0.001; female, 53.8% vs. 28.5%, p = 0.009). The high SARC-F group also demonstrated a lower body mass index (21.1 ± 3.2 vs. 24.0 ± 3.8 kg/m², p < 0.001) and a higher prevalence of diabetes mellitus (38.5% vs. 20.2%, p = 0.036). Right-sided tumors were more frequently observed in patients with high SARC-F scores (53.8% vs. 28.0%, p = 0.012). With respect to inflammatory markers, patients in the high SARC-F group exhibited significantly higher preoperative C-reactive protein levels and neutrophil-to-lymphocyte ratios compared with the low SARC-F group (CRP: 2.6 ± 4.2 vs. 0.9 ± 1.8 mg/dL, p = 0.026; NLR: 3.7 ± 1.8 vs. 2.9 ± 2.5, p = 0.002). No significant differences were observed between the groups in terms of hypertension, preoperative carcinoembryonic antigen levels, or ASA physical status classification. 2. Postoperative pathologic outcomes Postoperative pathologic findings are presented in Table 2. There were no significant differences between the high and low SARC-F groups with regard to T stage, N stage, M stage, histologic differentiation, tumor size, number of positive lymph nodes, lymphovascular invasion, perineural invasion, tumor budding, or microsatellite instability status. Notably, the mean number of retrieved lymph nodes was significantly higher in the high SARC-F group than in the low SARC-F group (28.7 ± 15.5 vs. 22.0 ± 11.0, p = 0.033), whereas the proportion of patients with fewer than 12 retrieved lymph nodes did not differ between groups. 3. Oncologic outcomes The mean follow-up duration was significantly shorter in the high SARC-F group compared with the low SARC-F group (34.5 ± 17.8 vs. 45.5 ± 16.5 months, p < 0.001) (Table 3). During follow-up, overall survival and cancer-specific survival were significantly lower in patients with high SARC-F scores than in those with low scores (OS: 82.9% vs. 92.0%, p = 0.036; CSS: 88.5% vs. 96.9%, p = 0.011). In contrast, disease-free survival did not differ significantly between the two groups (79.6% vs. 78.4%, p = 0.897). Recurrence occurred in 4 patients (15.4%) in the high SARC-F group and in 37 patients (19.2%) in the low SARC-F group ( p = 0.792). The distribution of recurrence patterns (systemic versus local) was also similar between groups. Kaplan–Meier survival curves demonstrated significantly worse overall survival and cancer-specific survival in the high SARC-F group, whereas disease-free survival remained comparable between the groups (Figure 2). These findings suggest that impaired preoperative functional status was associated with cancer-related mortality rather than tumor recurrence. 4. Prognostic factors for survival outcomes Univariate analyses of prognostic factors for overall survival, disease-free survival, and cancer-specific survival are summarized in Table 4. A high SARC-F score was significantly associated with poorer overall survival ( p = 0.036) and cancer-specific survival ( p = 0.011), but not with disease-free survival. Additional factors associated with worse outcomes included lower BMI, elevated preoperative CEA levels, higher inflammatory markers, advanced tumor stage, and the presence of lymphovascular or perineural invasion. Multivariate Cox regression analyses are shown in Table 5. After adjustment for relevant clinicopathologic variables, a higher BMI remained an independent prognostic factor for improved overall survival (HR 0.196; 95% CI 0.041–0.932; p = 0.040). Tumor sidedness (left-sided tumors) and lymphovascular invasion were independently associated with worse disease-free survival (HR 3.924; 95% CI 1.133–13.595; p = 0.031 and HR 3.914; 95% CI 1.609–9.519; p = 0.003, respectively). Importantly, a high preoperative SARC-F score emerged as an independent prognostic factor for cancer-specific survival (HR 19.602; 95% CI 1.292–297.475; p = 0.032), indicating that functional impairment prior to surgery was independently associated with CRC-related mortality. DISCUSSION In this study, we demonstrated that a high preoperative SARC-F score is closely associated with clinical and biological features characteristic of sarcopenia, including advanced age, female predominance, lower body mass index, higher prevalence of diabetes mellitus, right-sided tumor location, and elevated systemic inflammatory markers. Importantly, patients with high SARC-F scores experienced significantly worse overall and cancer-specific survival, and the SARC-F score emerged as an independent prognostic factor for cancer-specific survival after adjustment for established clinicopathologic variables. These findings indicate that functional impairment, as captured by a simple patient-reported questionnaire, reflects a clinically meaningful dimension of host vulnerability that influences cancer-related mortality in colorectal cancer. To our knowledge, this is the first study to systematically evaluate the prognostic impact of the SARC-F score on survival outcomes in a homogeneous cohort of patients with colorectal cancer. Sarcopenia has increasingly been recognized as a clinically important prognostic factor in colorectal cancer, with growing evidence linking impaired muscle health to poorer survival outcomes. A meta-analysis by Pamoukdjian et al.[ 30 ] eported that sarcopenia was associated with increased postoperative complications, chemotherapy-induced toxicities, and mortality risk in patients with colorectal cancer, while Blauwhoff-Buskermolen et al.[ 31 ] emonstrated that low muscle mass was significantly associated with reduced cancer-specific survival in patients with metastatic colorectal cancer undergoing palliative chemotherapy. More recently, a multicenter study evaluating the prognostic value of the SARC-F score in patients with advanced gastrointestinal cancers showed that a score ≥ 4 was independently associated with poorer overall survival, and subgroup analyses revealed significantly lower 1-year cumulative overall survival among patients with colorectal cancer and high SARC-F scores[ 28 ]. Consistent with and extending these findings, our study demonstrates that a high preoperative SARC-F score is associated with inferior survival outcomes in a homogeneous cohort of patients with colorectal cancer, supporting the concept that functional impairment represents a clinically meaningful dimension of host vulnerability beyond traditional tumor-related prognostic factors. Sarcopenia, characterized by progressive declines in muscle mass, strength, and physical function, is well known to be associated with advanced age, female sex, and lower body mass index [ 13 , 32 – 34 ]. Although the relationship between BMI and sarcopenia remains controversial, underweight status has consistently been linked to a higher likelihood of probable sarcopenia as defined by EWGSOP2 criteria[ 34 , 35 ]. n colorectal cancer, right-sided tumors have been reported to exhibit a higher prevalence of sarcopenia, increased postoperative complications, and poorer survival outcomes, potentially reflecting older age, greater inflammatory burden, and compromised nutritional status [ 36 ]. In addition, type 2 diabetes mellitus has been repeatedly associated with accelerated loss of skeletal muscle mass and strength in older adults [ 36 – 40 ]. Consistent with these observations, our study demonstrates that a high preoperative SARC-F score is strongly correlated with older age, female sex, lower BMI, right-sided tumor location, and a higher prevalence of diabetes mellitus. These findings support the validity of the SARC-F questionnaire as a functional assessment tool that captures not only impaired physical performance such as reduced gait speed and muscle strength but also a broader clinical profile characteristic of sarcopenia in patients with colorectal cancer [ 41 ]. The pathophysiology of sarcopenia is widely understood to involve chronic low-grade inflammation and sustained activation of pro-inflammatory cytokines, leading to muscle proteolysis and myocyte apoptosis [ 42 ]. Elevated inflammatory biomarkers such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been consistently associated with skeletal muscle loss, impaired physical function, and adverse survival outcomes[ 43 – 52 ]. At the molecular and functional levels, higher circulating levels of IL-6, TNF-α, and CRP have been linked to reduced appendicular muscle mass, diminished grip strength, and increased functional dependency in older adults[ 43 – 52 ]. In the oncologic setting, systemic inflammation has also been shown to adversely affect colorectal cancer outcomes. Goyal et al. demonstrated a dose-dependent association between preoperative CRP levels and colorectal cancer mortality[ 46 ], and multiple studies have identified elevated preoperative NLR as an independent predictor of poorer disease-free and cancer-specific survival in patients with colorectal cancer [ 47 – 49 ]. Taken together, these findings support the concept that chronic inflammation represents a shared biological pathway linking functional decline, sarcopenia, and cancer-specific mortality, providing a plausible mechanistic basis for the observed association between high SARC-F scores and inferior oncologic outcomes in our study. Interestingly, patients with high SARC-F scores in our study had a significantly higher number of retrieved lymph nodes compared with those with lower scores. Although sarcopenia is generally associated with frailty and adverse surgical outcomes, this seemingly paradoxical finding may be explained by differences in visceral fat distribution. Previous studies have demonstrated that visceral obesity, rather than body mass index, is a key determinant of technical difficulty during colorectal surgery and is associated with reduced lymph node harvest due to obscured surgical planes and challenging mesenteric dissection [ 53 , 54 ]. Excessive mesenteric fat can further complicate pathological lymph node identification and retrieval [ 53 , 54 ]. Although visceral fat was not directly measured in our cohort, it is plausible that the relatively lower visceral adiposity typically observed in sarcopenic patients may have facilitated clearer anatomical visualization and more effective lymphadenectomy. This observation highlights the complex interplay between body composition, functional status, and oncologic surgical quality, suggesting that sarcopenia—as reflected by a high SARC-F score—may paradoxically be associated with more favorable technical conditions for lymph node dissection. In the present study, distinct prognostic factors were identified for different survival endpoints, underscoring the importance of endpoint-specific interpretation. Notably, the SARC-F score emerged as an independent prognostic factor for cancer-specific survival, whereas body mass index was associated with overall survival, and tumor sidedness and lymphovascular invasion were predictive of disease-free survival. Cancer-specific survival provides a direct measure of cancer lethality that is less influenced by competing risks, which is particularly relevant in elderly patients and those with substantial comorbidities, in whom non-cancer-related mortality may obscure the true impact of cancer and its treatment[ 55 ]. Accordingly, the association between a high SARC-F score and poorer cancer-specific survival suggests that functional impairment reflects cancer-related vulnerability rather than merely general physical frailty. The favorable association between higher body mass index and overall survival observed in our study is consistent with the so-called obesity paradox described in colorectal cancer, although this concept remains controversial[ 56 , 57 ]. In addition, the poorer disease-free survival associated with left-sided tumors in our cohort may be partially explained by the higher prevalence of microsatellite instability–high tumors in right-sided colorectal cancer, which are known to exhibit enhanced immunogenicity and a lower risk of recurrence in early-stage disease [58,59]. Given that the majority of patients in our study had stage I to III disease, this biological distinction may have contributed to the observed differences in disease-free survival. Several limitations of this study should be acknowledged. First, this was a retrospective, single-center analysis with a relatively limited sample size, which may restrict the generalizability of our findings. Second, objective measures of sarcopenia, such as radiologic skeletal muscle mass and handgrip strength, were not available, precluding direct comparison between functional and morphologic assessments. Third, the SARC-F questionnaire relies on patient self-reporting, which may introduce inter-individual variability; however, this also reflects its practical applicability in routine clinical settings. In addition, the shorter follow-up duration and smaller number of patients in the high SARC-F group may have limited the statistical robustness of survival analyses, and the multivariate results should therefore be interpreted with caution. Despite these limitations, our findings provide clinically relevant insights into the prognostic significance of functional impairment in colorectal cancer. Future large-scale, prospective, multicenter studies with longer and balanced follow-up are warranted to validate our results and to further clarify the complementary roles of functional and objective sarcopenia assessments in prognostic stratification of patients with colorectal cancer. CONCLUSIONS Our findings demonstrate that a high preoperative SARC-F score is independently associated with inferior cancer-specific survival in patients with colorectal cancer. This suggests that functional impairment reflects a clinically meaningful dimension of host vulnerability that influences cancer-related mortality beyond traditional tumor-related prognostic factors. Given its simplicity and feasibility, the SARC-F questionnaire may serve as a practical tool for preoperative prognostic stratification and patient-centered risk assessment in colorectal cancer. Declarations Acknowledgements None. Author Disclosures None to declare. Funding declarations None to declare. Data availability The data that support the findings of this study are available on request from the corresponding author, S.U Bae. The data are not publicly available due to their containing information that could compromise the privacy of research participants. Author contributions Dain Shin contributed to data curation and methodology, and drafted the original manuscript. Sung Uk Bae conceived and designed the study, provided resources, conducted the investigation, and supervised the research; he also reviewed and edited the manuscript. Woon Kyung Jeong contributed to resource acquisition. Sung Kyu Baek also contributed to resource acquisition. References Siegel, R.L., A.N. Giaquinto, and A. Jemal, Cancer statistics, 2024. CA Cancer J Clin, 2024. 74 (1): p. 12–49. Ryu, H.S., et al., Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment. Ann Coloproctol, 2024. 40 (2): p. 89–113. Ratto, C., et al., Prognostic factors in colorectal cancer: Literature review for clinical application. Diseases of the Colon & Rectum, 1998. 41 (8): p. 1033–1049. De Divitiis, C., et al., Prognostic and predictive response factors in colorectal cancer patients: between hope and reality. 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Cancer Epidemiology, Biomarkers & Prevention, 2014. 23 (8): p. 1609–1618. Shibutani, M., et al., A high preoperative neutrophil-to-lymphocyte ratio is associated with poor survival in patients with colorectal cancer. Anticancer Res, 2013. 33 (8): p. 3291–4. Shin, J.S., K.W. Suh, and S.Y. Oh, Preoperative neutrophil to lymphocyte ratio predicts survival in patients with T1-2N0 colorectal cancer. Journal of Surgical Oncology, 2015. 112 (6): p. 654–657. Kubo, H., et al., The Prognostic Value of Preoperative Neutrophil-to-Lymphocyte Ratio in Colorectal Cancer. World J Surg, 2016. 40 (11): p. 2796–2802. Song, W.J., et al., Association between body composition measured by bioelectrical impedance analysis and platelet-to-lymphocyte ratio in colorectal cancer. Korean J Clin Oncol, 2019. 15 (1): p. 7–14. Eray, I.C., et al., The role of C-reactive protein ratio in predicting mortality in patients with Fournier gangrene. Ann Coloproctol, 2023. 39 (3): p. 223–230. An, S.H. and I.Y. Kim, Can pretreatment platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios predict long-term oncologic outcomes after preoperative chemoradiation followed by surgery for locally advanced rectal cancer? Ann Coloproctol, 2022. 38 (3): p. 253–261. Cawthorn, S.J., N.M. Gibbs, and C.G. Marks, Clearance technique for the detection of lymph nodes in colorectal cancer. Br J Surg, 1986. 73 (1): p. 58–60. Watanabe, J., et al., The impact of visceral obesity on surgical outcomes of laparoscopic surgery for colon cancer. Int J Colorectal Dis, 2014. 29 (3): p. 343–51. Dickman, P.W. and H.O. Adami, Interpreting trends in cancer patient survival. J Intern Med, 2006. 260 (2): p. 103–17. Li, Y., et al., The obesity paradox in patients with colorectal cancer: a systematic review and meta-analysis. Nutr Rev, 2022. 80 (7): p. 1755–1768. Simillis, C., et al., A systematic review and meta-analysis assessing the impact of body mass index on long-term survival outcomes after surgery for colorectal cancer. European Journal of Cancer, 2022. 172 : p. 237–251. Tables Tables 1 to 5 are available in the supplementary files section Additional Declarations No competing interests reported. Supplementary Files Tables.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 23 Feb, 2026 Reviewers agreed at journal 13 Feb, 2026 Reviewers invited by journal 13 Feb, 2026 Editor invited by journal 09 Jan, 2026 Editor assigned by journal 09 Jan, 2026 Submission checks completed at journal 09 Jan, 2026 First submitted to journal 04 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-8510816","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":591808601,"identity":"86baf6f0-4110-4618-971a-376a32db9010","order_by":0,"name":"Dain Shin","email":"","orcid":"","institution":"Keimyung University","correspondingAuthor":false,"prefix":"","firstName":"Dain","middleName":"","lastName":"Shin","suffix":""},{"id":591808603,"identity":"8e88da47-5e8a-4991-a4a4-8d8c266b2c64","order_by":1,"name":"Sung Uk Bae","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYFACHoYDIIqNmbHhwMcGEJOx8QBhLQkMDPzszQcfzoRoaQBpkcCnhQGkRbLnWLIxbwNEDK8W+fazBw/+/GGTZ3Ajx0zadoddnm774YYDjDts6nBpMTiTl3CYJyGtGKwl90xysdmZRKCWM2k4bTFgyDE4zJBwOHEDWEsbc+K2AyAtbYdxO6z/jcHBHzAtlm31idvOPwRp+Y/b+zdyDA7wALXMBHkfaHjithtgWw7gdtiNd0C/pKUl9oMCubftOFAL0JbEtmTJBpwOyz388YeNTWIbKCp/tlUDHZb+8MHHNjt+nA7DDhJIVD8KRsEoGAWjABUAADAZam4gwrzGAAAAAElFTkSuQmCC","orcid":"","institution":"Keimyung University Dongsan Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Sung","middleName":"Uk","lastName":"Bae","suffix":""},{"id":591808605,"identity":"ed8587e1-4885-4e58-8553-83943f9e08da","order_by":2,"name":"Woon Kyung Jeong","email":"","orcid":"","institution":"Keimyung University Dongsan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Woon","middleName":"Kyung","lastName":"Jeong","suffix":""},{"id":591808609,"identity":"ecda6387-e8bb-4215-9d92-4288ceadb41b","order_by":3,"name":"Seong Kyu Baek","email":"","orcid":"","institution":"Keimyung University Dongsan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Seong","middleName":"Kyu","lastName":"Baek","suffix":""}],"badges":[],"createdAt":"2026-01-04 06:53:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8510816/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8510816/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103049965,"identity":"89084d6a-426a-42c8-a205-49949bb196d0","added_by":"auto","created_at":"2026-02-20 07:47:28","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":523750,"visible":true,"origin":"","legend":"\u003cp\u003eA total of 351 advanced patients with CRC who underwent curative resection between July 2019 and June 2021 were initially reviewed. Of these, 132 patients were excluded due to the following criteria: synchronous or prior malignancies (n = 29), malignancies other than adenocarcinoma (n = 19), familial adenomatous polyposis or hereditary non-polyposis CRC (n = 1), incomplete blood cell count information (n = 38), and non-response to the SARC-F questionnaire (n = 45). Therefore, 219 patients were included and classified into two groups based on SARC-F score: high SARC-F group (score ≥4, n = 26) and low SARC-F group (score \u0026lt;4, n = 193).\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8510816/v1/c645ec0cf8d582bbe09ad3b5.jpg"},{"id":102991490,"identity":"c8a30e30-8219-4b4d-bdd1-b9cc8b7caf9d","added_by":"auto","created_at":"2026-02-19 11:32:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":180802,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Overall survival (OS): The high SARC-F group showed significantly lower OS compared to the low SARC-F group (82.9% vs. 92.0%, p = 0.036). (B) Disease-free survival (DFS): No significant difference was observed between the high and low SARC-F groups in terms of DFS (79.6% vs. 78.4%, p = 0.897). (C) Cancer-specific survival (CSS): Patients in the high SARC-F group (score ≥4) demonstrated significantly lower CSS compared to those in the low SARC-F group (score \u0026lt;4) (88.5% vs. 96.9%, p = 0.011).\u003c/p\u003e\n\u003cp\u003eThe number of patients at risk at each time point is presented below each graph.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8510816/v1/7399c048b730ea3d41d9f7f3.jpg"},{"id":103051118,"identity":"6218cec0-6518-4333-b7a8-03534f18ecdf","added_by":"auto","created_at":"2026-02-20 07:58:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1389364,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8510816/v1/8adfccd9-a29c-442d-ba3a-1c8bc635ed4c.pdf"},{"id":103049856,"identity":"dfca6926-77c8-4a3f-b29f-3f3f22cc26cb","added_by":"auto","created_at":"2026-02-20 07:46:52","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":42555,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8510816/v1/a388e6151c23c4f23ab6e4e2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic Impact of Preoperative SARC-F Score on Cancer-Specific Survival in Patients with Colorectal Cancer","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eColorectal cancer (CRC) remains a major global health burden and has recently become the second leading cause of cancer-related mortality in both men and women, with its incidence continuing to rise worldwide [1, 2]. Despite substantial advances in surgical techniques, systemic therapy, and perioperative management, long-term outcomes after curative resection remain heterogeneous. Traditionally, prognostic stratification in CRC has relied primarily on tumor-related factors, including depth of invasion, lymph node involvement, number of examined lymph nodes, serum carcinoembryonic antigen (CEA) levels, and the presence of bowel perforation\u0026nbsp;[3-5]. However, these parameters do not fully capture the wide variability in survival observed among patients with similar pathological stages.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Increasing evidence suggests that host-related factors play a critical role in determining oncologic outcomes in CRC. Patient-specific characteristics such as genetic background, immune and inflammatory status, nutritional reserve, body composition, and cancer-associated cachexia have been shown to significantly influence postoperative recovery, treatment tolerance, and long-term survival [6-11]. These observations underscore a growing recognition that CRC prognosis reflects not only tumor biology but also the patient’s physiological and functional resilience. Accordingly, the identification of prognostic tools that integrate host vulnerability into routine clinical assessment has become an important component of contemporary precision oncology.\u003c/p\u003e\n\u003cp\u003eSarcopenia, defined as a progressive and systemic skeletal muscle disorder characterized by declines in muscle mass, strength, and physical performance, has emerged as a particularly relevant host-related factor in oncology [12-14]. In patients with CRC and other solid malignancies, sarcopenia has been consistently associated with increased postoperative complications, reduced tolerance to chemotherapy, and inferior survival outcomes [15-23]. Most previous studies have assessed sarcopenia using radiologic measurements of skeletal muscle mass derived from computed tomography (CT) imaging. While informative, these approaches require specialized software, standardized imaging protocols, and technical expertise, which may limit their routine applicability in daily clinical practice. Moreover, muscle mass alone may not fully reflect functional impairment, which is increasingly recognized as a critical determinant of clinical outcomes.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; To address these limitations, the European Working Group on Sarcopenia in Older People (EWGSOP2) recommends the use of the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls (SARC-F) questionnaire as an initial screening tool for sarcopenia[12]. The SARC-F is a simple, self-reported instrument that assesses functional decline across five domains of daily activity. Although its sensitivity for detecting low muscle mass is modest, the SARC-F demonstrates high specificity and has been shown to reliably identify individuals at risk for adverse functional and clinical outcomes[24-26]. Importantly, recent studies suggest that the SARC-F score may capture a broader concept of functional and inflammatory vulnerability, rather than muscle quantity alone, thereby providing complementary prognostic information beyond radiologic sarcopenia.\u003c/p\u003e\n\u003cp\u003eEmerging evidence has linked high SARC-F scores to unfavorable outcomes in several malignancies, including urologic and gastrointestinal cancers [27, 28]. In patients undergoing colorectal cancer surgery, a high preoperative SARC-F score has been associated with increased postoperative morbidity[29]. However, despite the growing interest in functional assessment tools, the prognostic significance of the SARC-F score for long-term oncologic outcomes in colorectal cancer, particularly cancer-specific survival, has not been systematically evaluated in a homogeneous CRC cohort. Whether a simple preoperative functional assessment can independently predict oncologic prognosis beyond established clinicopathologic factors remains unclear.\u003c/p\u003e\n\u003cp\u003eTherefore, the present study aimed to investigate the prognostic impact of the preoperative SARC-F score on oncologic outcomes in patients undergoing curative resection for colorectal cancer. We hypothesized that a high SARC-F score, reflecting impaired functional reserve and host vulnerability, would be independently associated with inferior cancer-specific survival, thereby providing a clinically feasible tool for preoperative risk stratification in colorectal cancer.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003e1.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eEthical considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of Keimyung University Dongsan Medical Center (IRB No. 2022-12-040). Given the retrospective nature of the study and the use of anonymized clinical data, the requirement for written informed consent was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrospectively reviewed consecutive patients who underwent curative resection for colorectal cancer between July 2019 and June 2021 at Keimyung University Dongsan Medical Center, Daegu, Korea. All patients were of Asian ethnicity. To ensure cohort homogeneity and minimize confounding, patients were excluded if they met any of the following criteria: presence of synchronous or prior malignancies, histologic subtypes other than adenocarcinoma, diagnosis of familial adenomatous polyposis or Lynch syndrome, incomplete preoperative blood cell count data, or failure to complete the preoperative SARC-F questionnaire.\u003c/p\u003e\n\u003cp\u003eAmong 351 patients initially screened, 132 were excluded based on these criteria. The final study cohort consisted of 219 patients, who were subsequently stratified into two groups according to their preoperative SARC-F score: a high SARC-F group (score ≥4) and a low SARC-F group (score \u0026lt;4). Restricting the analysis to patients who completed the SARC-F questionnaire was intended to reduce clinical heterogeneity and allow consistent functional assessment across the cohort.\u003c/p\u003e\n\u003cp\u003e3.\u0026nbsp;\u003cstrong\u003eData collection and definitions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical, laboratory, and pathologic data were obtained from prospectively maintained institutional databases and electronic medical records. Baseline variables included age, sex, body mass index (BMI), comorbidities (hypertension and diabetes mellitus), tumor location, American Society of Anesthesiologists (ASA) physical status classification, and preoperative laboratory parameters, including carcinoembryonic antigen (CEA), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR). The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count obtained from preoperative blood tests.\u003c/p\u003e\n\u003cp\u003ePathologic variables included T stage, N stage, M stage, histologic differentiation, tumor size, number of retrieved and positive lymph nodes, lymphovascular invasion (LVI), perineural invasion (PNI), tumor budding, and microsatellite instability (MSI) status. Tumors were staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system.\u003c/p\u003e\n\u003cp\u003eMSI status was assessed using polymerase chain reaction (PCR) amplification of five microsatellite markers recommended by the National Cancer Institute (BAT25, BAT26, D5S346, D2S123, and D17S250). Tumors were classified as MSI-high if instability was detected in two or more markers, MSI-low if instability was detected in one marker, and microsatellite stable if no instability was detected.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4. SARC-F assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe SARC-F questionnaire was administered preoperatively at the time of hospital admission. The questionnaire consists of five self-reported items assessing strength, assistance with walking, ability to rise from a chair, ability to climb stairs, and history of falls. Each item is scored from 0 to 2, yielding a total score ranging from 0 to 10. Consistent with established recommendations, a total score of ≥4 was used to define a high SARC-F score, indicative of impaired functional status and probable sarcopenia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eOncologic\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;outcomes and definitions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOverall survival (OS) was defined as the interval from the date of surgery to death from any cause or last follow-up. Disease-free survival (DFS) was defined as the time from surgery to the first documented recurrence or last follow-up, with recurrence confirmed radiologically or histologically. Cancer-specific survival (CSS) was defined as the time from surgery to death attributable to colorectal cancer. Local recurrence was defined as tumor recurrence within the surgical field, whereas recurrence accompanied by distant metastasis was classified as systemic recurrence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e6. Statistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables were expressed as means with standard deviations, and categorical variables were presented as frequencies with percentages. The normality of continuous variables was assessed using the Shapiro–Wilk test. Comparisons between groups were performed using the independent t-test or Mann–Whitney U test for continuous variables, as appropriate, and the chi-square test or Fisher’s exact test for categorical variables.\u003c/p\u003e\n\u003cp\u003eSurvival outcomes were analyzed using the Kaplan–Meier method and compared using the log-rank test. Cox proportional hazards regression models were used to identify prognostic factors for OS, DFS, and CSS. Variables with a p-value \u0026lt;0.10 in univariate analyses were entered into multivariate models to reduce the risk of overfitting. Given the limited number of events in the high SARC-F group, multivariate analyses were considered exploratory in nature.\u003c/p\u003e\n\u003cp\u003eThe proportional hazards assumption was evaluated using Schoenfeld residuals. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. Based on prior literature, cutoff values for CEA and CRP were set at 5.0 ng/mL and 1.0 mg/L, respectively. A two-sided p-value \u0026lt;0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics version 27 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003e1.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eBaseline Characteristics of patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 219 patients included in the analysis, 193 (88.1%) had a low SARC-F score (\u0026lt;4), whereas 26 patients (11.9%) were classified into the high SARC-F group (score ≥4) (Figure 1). Baseline characteristics according to SARC-F status are summarized in Table 1. Patients with high SARC-F scores were significantly older and more likely to be female compared with those with low scores (76.5 ± 7.9 vs. 64.8 ± 11.6 years, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001; female, 53.8% vs. 28.5%, \u003cem\u003ep\u003c/em\u003e = 0.009). The high SARC-F group also demonstrated a lower body mass index (21.1 ± 3.2 vs. 24.0 ± 3.8 kg/m², \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) and a higher prevalence of diabetes mellitus (38.5% vs. 20.2%, \u003cem\u003ep\u003c/em\u003e = 0.036). Right-sided tumors were more frequently observed in patients with high SARC-F scores (53.8% vs. 28.0%, \u003cem\u003ep\u003c/em\u003e = 0.012).\u003c/p\u003e\n\u003cp\u003eWith respect to inflammatory markers, patients in the high SARC-F group exhibited significantly higher preoperative C-reactive protein levels and neutrophil-to-lymphocyte ratios compared with the low SARC-F group (CRP: 2.6 ± 4.2 vs. 0.9 ± 1.8 mg/dL, \u003cem\u003ep\u003c/em\u003e = 0.026; NLR: 3.7 ± 1.8 vs. 2.9 ± 2.5, \u003cem\u003ep\u003c/em\u003e = 0.002). No significant differences were observed between the groups in terms of hypertension, preoperative carcinoembryonic antigen levels, or ASA physical status classification.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePostoperative pathologic outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Postoperative pathologic findings are presented in Table 2. There were no significant differences between the high and low SARC-F groups with regard to T stage, N stage, M stage, histologic differentiation, tumor size, number of positive lymph nodes, lymphovascular invasion, perineural invasion, tumor budding, or microsatellite instability status. Notably, the mean number of retrieved lymph nodes was significantly higher in the high SARC-F group than in the low SARC-F group (28.7 ± 15.5 vs. 22.0 ± 11.0, p = 0.033), whereas the proportion of patients with fewer than 12 retrieved lymph nodes did not differ between groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eOncologic outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean follow-up duration was significantly shorter in the high SARC-F group compared with the low SARC-F group (34.5 ± 17.8 vs. 45.5 ± 16.5 months, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) (Table 3). During follow-up, overall survival and cancer-specific survival were significantly lower in patients with high SARC-F scores than in those with low scores (OS: 82.9% vs. 92.0%, \u003cem\u003ep\u003c/em\u003e = 0.036; CSS: 88.5% vs. 96.9%, \u003cem\u003ep\u003c/em\u003e = 0.011). In contrast, disease-free survival did not differ significantly between the two groups (79.6% vs. 78.4%, \u003cem\u003ep\u003c/em\u003e = 0.897). Recurrence occurred in 4 patients (15.4%) in the high SARC-F group and in 37 patients (19.2%) in the low SARC-F group (\u003cem\u003ep\u003c/em\u003e = 0.792). The distribution of recurrence patterns (systemic versus local) was also similar between groups. Kaplan–Meier survival curves demonstrated significantly worse overall survival and cancer-specific survival in the high SARC-F group, whereas disease-free survival remained comparable between the groups (Figure 2). These findings suggest that impaired preoperative functional status was associated with cancer-related mortality rather than tumor recurrence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePrognostic factors for survival outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUnivariate analyses of prognostic factors for overall survival, disease-free survival, and cancer-specific survival are summarized in Table 4. A high SARC-F score was significantly associated with poorer overall survival (\u003cem\u003ep\u003c/em\u003e = 0.036) and cancer-specific survival (\u003cem\u003ep\u003c/em\u003e = 0.011), but not with disease-free survival. Additional factors associated with worse outcomes included lower BMI, elevated preoperative CEA levels, higher inflammatory markers, advanced tumor stage, and the presence of lymphovascular or perineural invasion.\u003c/p\u003e\n\u003cp\u003eMultivariate Cox regression analyses are shown in Table 5. After adjustment for relevant clinicopathologic variables, a higher BMI remained an independent prognostic factor for improved overall survival (HR 0.196; 95% CI 0.041–0.932; \u003cem\u003ep\u003c/em\u003e = 0.040). Tumor sidedness (left-sided tumors) and lymphovascular invasion were independently associated with worse disease-free survival (HR 3.924; 95% CI 1.133–13.595; \u003cem\u003ep\u003c/em\u003e = 0.031 and HR 3.914; 95% CI 1.609–9.519; \u003cem\u003ep\u003c/em\u003e = 0.003, respectively). Importantly, a high preoperative SARC-F score emerged as an independent prognostic factor for cancer-specific survival (HR 19.602; 95% CI 1.292–297.475; \u003cem\u003ep\u003c/em\u003e = 0.032), indicating that functional impairment prior to surgery was independently associated with CRC-related mortality.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study, we demonstrated that a high preoperative SARC-F score is closely associated with clinical and biological features characteristic of sarcopenia, including advanced age, female predominance, lower body mass index, higher prevalence of diabetes mellitus, right-sided tumor location, and elevated systemic inflammatory markers. Importantly, patients with high SARC-F scores experienced significantly worse overall and cancer-specific survival, and the SARC-F score emerged as an independent prognostic factor for cancer-specific survival after adjustment for established clinicopathologic variables. These findings indicate that functional impairment, as captured by a simple patient-reported questionnaire, reflects a clinically meaningful dimension of host vulnerability that influences cancer-related mortality in colorectal cancer. To our knowledge, this is the first study to systematically evaluate the prognostic impact of the SARC-F score on survival outcomes in a homogeneous cohort of patients with colorectal cancer.\u003c/p\u003e \u003cp\u003eSarcopenia has increasingly been recognized as a clinically important prognostic factor in colorectal cancer, with growing evidence linking impaired muscle health to poorer survival outcomes. A meta-analysis by Pamoukdjian et al.[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] eported that sarcopenia was associated with increased postoperative complications, chemotherapy-induced toxicities, and mortality risk in patients with colorectal cancer, while Blauwhoff-Buskermolen et al.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] emonstrated that low muscle mass was significantly associated with reduced cancer-specific survival in patients with metastatic colorectal cancer undergoing palliative chemotherapy. More recently, a multicenter study evaluating the prognostic value of the SARC-F score in patients with advanced gastrointestinal cancers showed that a score\u0026thinsp;\u0026ge;\u0026thinsp;4 was independently associated with poorer overall survival, and subgroup analyses revealed significantly lower 1-year cumulative overall survival among patients with colorectal cancer and high SARC-F scores[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Consistent with and extending these findings, our study demonstrates that a high preoperative SARC-F score is associated with inferior survival outcomes in a homogeneous cohort of patients with colorectal cancer, supporting the concept that functional impairment represents a clinically meaningful dimension of host vulnerability beyond traditional tumor-related prognostic factors.\u003c/p\u003e \u003cp\u003eSarcopenia, characterized by progressive declines in muscle mass, strength, and physical function, is well known to be associated with advanced age, female sex, and lower body mass index [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Although the relationship between BMI and sarcopenia remains controversial, underweight status has consistently been linked to a higher likelihood of probable sarcopenia as defined by EWGSOP2 criteria[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. n colorectal cancer, right-sided tumors have been reported to exhibit a higher prevalence of sarcopenia, increased postoperative complications, and poorer survival outcomes, potentially reflecting older age, greater inflammatory burden, and compromised nutritional status [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In addition, type 2 diabetes mellitus has been repeatedly associated with accelerated loss of skeletal muscle mass and strength in older adults [\u003cspan additionalcitationids=\"CR37 CR38 CR39\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Consistent with these observations, our study demonstrates that a high preoperative SARC-F score is strongly correlated with older age, female sex, lower BMI, right-sided tumor location, and a higher prevalence of diabetes mellitus. These findings support the validity of the SARC-F questionnaire as a functional assessment tool that captures not only impaired physical performance such as reduced gait speed and muscle strength but also a broader clinical profile characteristic of sarcopenia in patients with colorectal cancer [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe pathophysiology of sarcopenia is widely understood to involve chronic low-grade inflammation and sustained activation of pro-inflammatory cytokines, leading to muscle proteolysis and myocyte apoptosis [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Elevated inflammatory biomarkers such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been consistently associated with skeletal muscle loss, impaired physical function, and adverse survival outcomes[\u003cspan additionalcitationids=\"CR44 CR45 CR46 CR47 CR48 CR49 CR50 CR51\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. At the molecular and functional levels, higher circulating levels of IL-6, TNF-α, and CRP have been linked to reduced appendicular muscle mass, diminished grip strength, and increased functional dependency in older adults[\u003cspan additionalcitationids=\"CR44 CR45 CR46 CR47 CR48 CR49 CR50 CR51\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. In the oncologic setting, systemic inflammation has also been shown to adversely affect colorectal cancer outcomes. Goyal et al. demonstrated a dose-dependent association between preoperative CRP levels and colorectal cancer mortality[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e], and multiple studies have identified elevated preoperative NLR as an independent predictor of poorer disease-free and cancer-specific survival in patients with colorectal cancer [\u003cspan additionalcitationids=\"CR48\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Taken together, these findings support the concept that chronic inflammation represents a shared biological pathway linking functional decline, sarcopenia, and cancer-specific mortality, providing a plausible mechanistic basis for the observed association between high SARC-F scores and inferior oncologic outcomes in our study.\u003c/p\u003e \u003cp\u003eInterestingly, patients with high SARC-F scores in our study had a significantly higher number of retrieved lymph nodes compared with those with lower scores. Although sarcopenia is generally associated with frailty and adverse surgical outcomes, this seemingly paradoxical finding may be explained by differences in visceral fat distribution. Previous studies have demonstrated that visceral obesity, rather than body mass index, is a key determinant of technical difficulty during colorectal surgery and is associated with reduced lymph node harvest due to obscured surgical planes and challenging mesenteric dissection [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. Excessive mesenteric fat can further complicate pathological lymph node identification and retrieval [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. Although visceral fat was not directly measured in our cohort, it is plausible that the relatively lower visceral adiposity typically observed in sarcopenic patients may have facilitated clearer anatomical visualization and more effective lymphadenectomy. This observation highlights the complex interplay between body composition, functional status, and oncologic surgical quality, suggesting that sarcopenia\u0026mdash;as reflected by a high SARC-F score\u0026mdash;may paradoxically be associated with more favorable technical conditions for lymph node dissection.\u003c/p\u003e \u003cp\u003eIn the present study, distinct prognostic factors were identified for different survival endpoints, underscoring the importance of endpoint-specific interpretation. Notably, the SARC-F score emerged as an independent prognostic factor for cancer-specific survival, whereas body mass index was associated with overall survival, and tumor sidedness and lymphovascular invasion were predictive of disease-free survival. Cancer-specific survival provides a direct measure of cancer lethality that is less influenced by competing risks, which is particularly relevant in elderly patients and those with substantial comorbidities, in whom non-cancer-related mortality may obscure the true impact of cancer and its treatment[\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. Accordingly, the association between a high SARC-F score and poorer cancer-specific survival suggests that functional impairment reflects cancer-related vulnerability rather than merely general physical frailty. The favorable association between higher body mass index and overall survival observed in our study is consistent with the so-called obesity paradox described in colorectal cancer, although this concept remains controversial[\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. In addition, the poorer disease-free survival associated with left-sided tumors in our cohort may be partially explained by the higher prevalence of microsatellite instability\u0026ndash;high tumors in right-sided colorectal cancer, which are known to exhibit enhanced immunogenicity and a lower risk of recurrence in early-stage disease [58,59]. Given that the majority of patients in our study had stage I to III disease, this biological distinction may have contributed to the observed differences in disease-free survival.\u003c/p\u003e \u003cp\u003eSeveral limitations of this study should be acknowledged. First, this was a retrospective, single-center analysis with a relatively limited sample size, which may restrict the generalizability of our findings. Second, objective measures of sarcopenia, such as radiologic skeletal muscle mass and handgrip strength, were not available, precluding direct comparison between functional and morphologic assessments. Third, the SARC-F questionnaire relies on patient self-reporting, which may introduce inter-individual variability; however, this also reflects its practical applicability in routine clinical settings. In addition, the shorter follow-up duration and smaller number of patients in the high SARC-F group may have limited the statistical robustness of survival analyses, and the multivariate results should therefore be interpreted with caution. Despite these limitations, our findings provide clinically relevant insights into the prognostic significance of functional impairment in colorectal cancer. Future large-scale, prospective, multicenter studies with longer and balanced follow-up are warranted to validate our results and to further clarify the complementary roles of functional and objective sarcopenia assessments in prognostic stratification of patients with colorectal cancer.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eOur findings demonstrate that a high preoperative SARC-F score is independently associated with inferior cancer-specific survival in patients with colorectal cancer. This suggests that functional impairment reflects a clinically meaningful dimension of host vulnerability that influences cancer-related mortality beyond traditional tumor-related prognostic factors. Given its simplicity and feasibility, the SARC-F questionnaire may serve as a practical tool for preoperative prognostic stratification and patient-centered risk assessment in colorectal cancer.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Disclosures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;None to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available on request from the corresponding author, S.U Bae. The data are not publicly available due to their containing information that could compromise the privacy of research participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDain Shin contributed to data curation and methodology, and drafted the original manuscript. Sung Uk Bae conceived and designed the study, provided resources, conducted the investigation, and supervised the research; he also reviewed and edited the manuscript. Woon Kyung Jeong contributed to resource acquisition. Sung Kyu Baek also contributed to resource acquisition.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSiegel, R.L., A.N. Giaquinto, and A. 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No, \u003cem\u003eAssociations between Sarcopenia and Metabolic Risk Factors: A Systematic Review and Meta-Analysis.\u003c/em\u003e J Obes Metab Syndr, 2018. \u003cstrong\u003e27\u003c/strong\u003e(3): p. 175\u0026ndash;185.\u003c/li\u003e\n\u003cli\u003eKim, K.S., et al., \u003cem\u003eType 2 diabetes is associated with low muscle mass in older adults.\u003c/em\u003e Geriatr Gerontol Int, 2014. \u003cstrong\u003e14 Suppl 1\u003c/strong\u003e: p. 115\u0026ndash;21.\u003c/li\u003e\n\u003cli\u003eMalmstrom, T.K., et al., \u003cem\u003eSARC-F: a symptom score to predict persons with sarcopenia at risk for poor functional outcomes.\u003c/em\u003e J Cachexia Sarcopenia Muscle, 2016. \u003cstrong\u003e7\u003c/strong\u003e(1): p. 28\u0026ndash;36.\u003c/li\u003e\n\u003cli\u003eBano, G., et al., \u003cem\u003eInflammation and sarcopenia: A systematic review and meta-analysis.\u003c/em\u003e Maturitas, 2017. \u003cstrong\u003e96\u003c/strong\u003e: p. 10\u0026ndash;15.\u003c/li\u003e\n\u003cli\u003eBautmans, I., et al., \u003cem\u003eGrip work estimation during sustained maximal contraction: validity and relationship with dependency and inflammation in elderly persons.\u003c/em\u003e J Nutr Health Aging, 2011. \u003cstrong\u003e15\u003c/strong\u003e(8): p. 731\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eAlem\u0026aacute;n, H., et al., \u003cem\u003eLongitudinal evidence on the association between interleukin-6 and C-reactive protein with the loss of total appendicular skeletal muscle in free-living older men and women.\u003c/em\u003e Age Ageing, 2011. \u003cstrong\u003e40\u003c/strong\u003e(4): p. 469\u0026ndash;75.\u003c/li\u003e\n\u003cli\u003eHaren, M.T., et al., \u003cem\u003eHigher C-reactive protein and soluble tumor necrosis factor receptor levels are associated with poor physical function and disability: a cross-sectional analysis of a cohort of late middle-aged African Americans.\u003c/em\u003e J Gerontol A Biol Sci Med Sci, 2010. \u003cstrong\u003e65\u003c/strong\u003e(3): p. 274\u0026ndash;81.\u003c/li\u003e\n\u003cli\u003eGoyal, A., et al., \u003cem\u003eC-Reactive Protein and Colorectal Cancer Mortality in U.S. Adults.\u003c/em\u003e Cancer Epidemiology, Biomarkers \u0026amp; Prevention, 2014. \u003cstrong\u003e23\u003c/strong\u003e(8): p. 1609\u0026ndash;1618.\u003c/li\u003e\n\u003cli\u003eShibutani, M., et al., \u003cem\u003eA high preoperative neutrophil-to-lymphocyte ratio is associated with poor survival in patients with colorectal cancer.\u003c/em\u003e Anticancer Res, 2013. \u003cstrong\u003e33\u003c/strong\u003e(8): p. 3291\u0026ndash;4.\u003c/li\u003e\n\u003cli\u003eShin, J.S., K.W. Suh, and S.Y. Oh, \u003cem\u003ePreoperative neutrophil to lymphocyte ratio predicts survival in patients with T1-2N0 colorectal cancer.\u003c/em\u003e Journal of Surgical Oncology, 2015. \u003cstrong\u003e112\u003c/strong\u003e(6): p. 654\u0026ndash;657.\u003c/li\u003e\n\u003cli\u003eKubo, H., et al., \u003cem\u003eThe Prognostic Value of Preoperative Neutrophil-to-Lymphocyte Ratio in Colorectal Cancer.\u003c/em\u003e World J Surg, 2016. \u003cstrong\u003e40\u003c/strong\u003e(11): p. 2796\u0026ndash;2802.\u003c/li\u003e\n\u003cli\u003eSong, W.J., et al., \u003cem\u003eAssociation between body composition measured by bioelectrical impedance analysis and platelet-to-lymphocyte ratio in colorectal cancer.\u003c/em\u003e Korean J Clin Oncol, 2019. \u003cstrong\u003e15\u003c/strong\u003e(1): p. 7\u0026ndash;14.\u003c/li\u003e\n\u003cli\u003eEray, I.C., et al., \u003cem\u003eThe role of C-reactive protein ratio in predicting mortality in patients with Fournier gangrene.\u003c/em\u003e Ann Coloproctol, 2023. \u003cstrong\u003e39\u003c/strong\u003e(3): p. 223\u0026ndash;230.\u003c/li\u003e\n\u003cli\u003eAn, S.H. and I.Y. Kim, \u003cem\u003eCan pretreatment platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios predict long-term oncologic outcomes after preoperative chemoradiation followed by surgery for locally advanced rectal cancer?\u003c/em\u003e Ann Coloproctol, 2022. \u003cstrong\u003e38\u003c/strong\u003e(3): p. 253\u0026ndash;261.\u003c/li\u003e\n\u003cli\u003eCawthorn, S.J., N.M. Gibbs, and C.G. Marks, \u003cem\u003eClearance technique for the detection of lymph nodes in colorectal cancer.\u003c/em\u003e Br J Surg, 1986. \u003cstrong\u003e73\u003c/strong\u003e(1): p. 58\u0026ndash;60.\u003c/li\u003e\n\u003cli\u003eWatanabe, J., et al., \u003cem\u003eThe impact of visceral obesity on surgical outcomes of laparoscopic surgery for colon cancer.\u003c/em\u003e Int J Colorectal Dis, 2014. \u003cstrong\u003e29\u003c/strong\u003e(3): p. 343\u0026ndash;51.\u003c/li\u003e\n\u003cli\u003eDickman, P.W. and H.O. Adami, \u003cem\u003eInterpreting trends in cancer patient survival.\u003c/em\u003e J Intern Med, 2006. \u003cstrong\u003e260\u003c/strong\u003e(2): p. 103\u0026ndash;17.\u003c/li\u003e\n\u003cli\u003eLi, Y., et al., \u003cem\u003eThe obesity paradox in patients with colorectal cancer: a systematic review and meta-analysis.\u003c/em\u003e Nutr Rev, 2022. \u003cstrong\u003e80\u003c/strong\u003e(7): p. 1755\u0026ndash;1768.\u003c/li\u003e\n\u003cli\u003eSimillis, C., et al., \u003cem\u003eA systematic review and meta-analysis assessing the impact of body mass index on long-term survival outcomes after surgery for colorectal cancer.\u003c/em\u003e European Journal of Cancer, 2022. \u003cstrong\u003e172\u003c/strong\u003e: p. 237\u0026ndash;251.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 5 are available in the supplementary files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Colorectal Neoplasms, Sarcopenia, Frailty, Prognosis, Survival Analysis, Inflammation","lastPublishedDoi":"10.21203/rs.3.rs-8510816/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8510816/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSarcopenia adversely affects outcomes in patients with colorectal cancer (CRC); however, the prognostic significance of functional sarcopenia screening tools such as the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls (SARC-F) questionnaire remains unclear.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aimed to evaluate the prognostic impact of preoperative SARC-F scores on oncologic outcomes in patients with CRC.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed 219 patients who underwent curative resection for CRC and completed the SARC-F questionnaire preoperatively between July 2019 and June 2021. Patients with a SARC-F score\u0026thinsp;\u0026ge;\u0026thinsp;4 were classified into the high SARC-F group.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the 219 patients, 26 (11.9%) had high SARC-F scores. Compared with the low SARC-F group, patients with high SARC-F scores were older, more frequently female, had lower body mass index, a higher prevalence of diabetes mellitus, more right-sided tumors, and elevated preoperative C-reactive protein and neutrophil-to-lymphocyte ratio levels (all \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Pathologic characteristics were comparable between groups, except for a higher number of retrieved lymph nodes in the high SARC-F group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.033). Overall survival and cancer-specific survival were significantly lower in the high SARC-F group (OS: 82.9% vs. 92.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.036; CSS: 88.5% vs. 96.9%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011), whereas disease-free survival did not differ significantly. In multivariate analysis, a SARC-F score\u0026thinsp;\u0026ge;\u0026thinsp;4 independently predicted poorer cancer-specific survival (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032), while higher body mass index was associated with improved overall survival, and left-sided tumor location and lymphovascular invasion were independent predictors of disease-free survival.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eA high preoperative SARC-F score is independently associated with inferior cancer-specific survival in patients with CRC, highlighting the prognostic relevance of functional impairment. The SARC-F questionnaire may serve as a simple and clinically feasible tool for preoperative risk stratification in colorectal cancer.\u003c/p\u003e","manuscriptTitle":"Prognostic Impact of Preoperative SARC-F Score on Cancer-Specific Survival in Patients with Colorectal Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-19 11:32:05","doi":"10.21203/rs.3.rs-8510816/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-23T17:57:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"232710549717781995325587843960709539646","date":"2026-02-13T14:21:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-13T12:49:50+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-09T10:02:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-09T09:13:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-09T09:11:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2026-01-04T06:36:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"91fdcd00-2e49-46ba-a99d-ab86fcaa8f89","owner":[],"postedDate":"February 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-19T11:32:05+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-19 11:32:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8510816","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8510816","identity":"rs-8510816","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}