Prevalence and Prognostic Impact of Cancer Cachexia in Patients with Bladder Cancer: A Multicenter Retrospective Study

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Although sarcopenia has been reported as a prognostic factor in bladder cancer, the prevalence and prognostic significance of cancer cachexia defined by standardized criteria remain unclear. Methods We retrospectively analyzed patients who received first-line systemic chemotherapy for urothelial carcinoma at three institutions. Cancer cachexia was defined according to the 2011 European Palliative Care Research Collaborative (EPCRC) criteria based on weight loss, body mass index, and CT-derived L3 skeletal muscle index. Baseline cachexia was assessed within 6 months prior to treatment initiation, and follow-up cachexia was evaluated during treatment. Survival outcomes and prognostic factors were analyzed using Kaplan–Meier methods, logistic regression, and Cox proportional hazards models. Results Among 150 eligible patients, 30% met the criteria for cachexia at treatment initiation. The cumulative prevalence increased to 57.3% within 3 months and reached 74% at some point during the observation period. Cachexia was significantly associated with advanced disease stage and sarcopenia. Overall survival was significantly shorter in patients who developed cachexia, with a median survival of 827 days (95% confidence interval 586–1098). Multivariate Cox analysis identified cancer cachexia and elevated C-reactive protein (CRP) (> 0.4 mg/dL) as independent predictors of poor overall survival. Conclusion Cancer cachexia is highly prevalent in patients with bladder cancer receiving first-line chemotherapy and is independently associated with reduced survival. Early identification of metabolic deterioration may improve risk stratification and guide supportive interventions. bladder cancer cancer cachexia sarcopenia skeletal muscle index chemotherapy Figures Figure 1 Figure 2 INTRODUCTION Cancer cachexia is defined as “a multifactorial syndrome characterized by a loss of skeletal muscle mass that cannot be fully reversed by nutritional support and that leads progressively to functional impairment” [ 1 ]. It occurs in 40–80% of patients with cancer, depending on tumor type [ 2 ]. Cancer cachexia is more common in gastrointestinal and lung cancers [ 3 ] but is relatively uncommon in hematological and breast cancers [ 4 ]. It significantly impacts quality of life (QOL), chemotherapy efficacy, and survival outcomes [ 3 , 5 ], underscoring the need for early intervention and treatment. Definitions and diagnostic criteria for cancer cachexia have varied across clinical trials [ 6 , 7 ]. In 2011, the European Palliative Care Research Collaborative (EPCRC) established diagnostic criteria for cancer cachexia, which include at least one of the following: (a) weight loss exceeding 5% in the past six months, (b) weight loss exceeding 2% combined with a body mass index (BMI) below 20 kg/m², or (c) weight loss exceeding 2% in the presence of sarcopenia [ 1 ]. These criteria are now widely accepted as the consensus standard for diagnosing cancer cachexia. Sarcopenia has been reported as a prognostic factor in bladder cancer [ 8 ], however sarcopenia and cachexia represent distinct clinical entities. Cachexia reflects a systemic inflammatory and metabolic state that may have greater clinical impact than muscle mass alone. Despite its relevance, the prevalence and prognostic significance of cancer cachexia in bladder cancer remain insufficiently investigated, even though cachexia is known to adversely affect outcomes in other solid tumors [ 9 , 10 ]. Given these considerations, we conducted a multicenter retrospective study to evaluate the prevalence, risk factors, and prognostic impac t of cancer cachexia in patients undergoing first-line chemotherapy for bladder cancer, using the standardized EPCRC 2011 criteria. This study aims to clarify the clinical significance of cachexia and provide evidence supporting improved risk stratification and early supportive interventions in this patient population. MATERIALS AND METHODS Patients We retrospectively reviewed patients who received first-line chemotherapy for bladder cancer at three institutions: Juntendo Hospital (April 2009–April 2024), Juntendo Shizuoka Hospital (November 2016–October 2023), and Juntendo Nerima Hospital (November 2009–March 2023). Among 227 patients, patients who received only perioperative chemotherapy were excluded, and 150 patients were included in the final analysis. Definition of Sarcopenia A cross-sectional CT image of the third lumbar vertebra (L3) was used to estimate skeletal muscle mass. Muscle cross-sectional area (cm²) was measured using SYNAPSE VINCENT version 6 (FUJIFILM Medical Systems, Nishiazabu, Minato, Japan). Skeletal Muscle Index (SMI) was calculated using the following equation: L3 SMI (cm²)/height² (m²). Sarcopenia was defined as SMI < 55 cm²/m² for men and SMI < 39 cm²/m² for women, as described in a previous study [ 11 ]. Definition of Cancer Cachexia Cancer cachexia was defined based on the EPCRC criteria [ 1 ]; weight loss exceeding 5%, or weight loss exceeding 2% with a BMI < 20 kg/m², or weight loss exceeding 2% accompanied by sarcopenia. Baseline cachexia was defined as meeting the criteria based on weight recorded within 6 months prior to chemotherapy initiation. The first time point at which a patient met the EPCRC criteria was considered the onset of follow-up cachexia. Patients who died before the next scheduled assessment were considered not to have reached cachexia onset unless already meeting criteria at their last recorded visit. Data Collection Patient data were retrospectively collected from medical records. Baseline was defined as the date of chemotherapy initiation. Age, sex, BMI, and blood parameters were recorded at baseline. Changes in chemotherapy regimen during the disease course were recorded. Statistical Analysis To identify risk factors for cachexia, categorical variables were compared using the Fisher’s exact test and multivariate logistic regression analysis was used for furthermore evaluation. Overall survival (OS) was defined as the duration from the first chemotherapy dose to death from any cause. Survival analysis was conducted using the Kaplan-Meier method and log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Factors identified in univariate analysis were further examined using multivariate Cox regression with the enter method to identify independent predictors of OS. Statistical analysis was performed using EZR software. A p-value < 0.05 was considered statistically significant. RESULTS Patient Characteristics A total of 150 patients met the eligibility criteria for this study. The cohort consisted of 113 men (75%) and 37 women (25%). Twenty-seven patients (18%) had concurrent upper urinary tract carcinoma (Table 1 ). Baseline TNM classification was as follows: T stage: T0, 17 (11.3%); T1, 8 (5.3%); T2, 75 (50.0%); T3, 34 (22.7%); T4, 16 (10.7%), N stage: N0, 98 (65.3%); N1, 10 (6.7%); N2, 34 (22.7%); N3, 8 (5.3%), M stage: M0, 101 (67.3%); M1, 49 (32.7%). Overall, 64.7% of patients had stage III or IV disease at treatment initiation. Median age was 73 years [IQR, 65–78), and the median BMI was 22.6 kg/m² [IQR, 20.0–24.8]. 36 patients (24%) had organ metastases at baseline. Chemotherapy regimens administered at any time included: GC 86 (57%), GCb 77 (51.3%), Gemcitabine monotherapy 4 (2.7%), MVAC 9 (6%), Avelumab 9 (6%), Pembrolizumab 43 (28.7%), Enfortumab vedotin 13 (8.7%), Nivolumab 2 (1.3%), and 8 others (5.3%). A total of 62 patients (41.3%) underwent radical cystectomy. Median SMI was 43.09 cm²/m² [IQR, 37.37–47.48] and 119 patients (79.3%) met the criteria for sarcopenia from the start of chemotherapy. Table 1 Patient characteristics Value N 150 Age (years) 73 [65–78] Sex Male 113 (75%) Female 37 (25%) BMI (kg/m 2 ) 22.6 [20.0-24.8] TNM classification T0(is,a) 17 (11.3%) T1 8 (5.3%) T2 75 (50%) T3 34 (22.7%) T4 16 (10.7%) N0 98 (65.3%) N1 10 (6.7%) N2 34 (22.7%) N3 8 (5.3%) M0 101 (67.3%) M1 49 (32.7%) Stage 0is 6 (4.0%) Ⅰ 5 (3.3%) Ⅱ 42 (28.0%) Ⅲ 48 (32.0%) Ⅳ 49 (32.7%) Visceral metastasis 36 (24%) upper ureteral carcinoma 27 (18%) combined Cystectomy 62 (41.3%) Chemotherapy GC 86 (57%) GCb 77 (51.3%) Gemcitabine monotherapy 4 (2.7%) MVAC 9 (6%) Avelumab 9 (6%) Pembrolizumab 43 (28.7%) Enfortumab vedotin 13 (8.7%) Nivolumab 2 (1.3%) other 8 (5.3%) multiple chemotherapy 67 (44.7%) Hemoglobin (g/dL) 12.1 [10.8–13.6] Albumin (g/dL) 3.9 [3.6–4.2] Creatinine (mg/dL) 0.87 [0.75–1.13] eGFR (mL/min/1.73m 2 ) 61.62 [43.88–75.33] CRP (mg/dL) 0.33 [0.1–1.34] Cachexia(baseline) 45 (30%) Sarcopenia(baseline) 119 (79.3%) SMI(cm 2 /m 2 )(baseline) 43.09 [37.37–47.48] Values are number (percent) of patients or median [IQR] BMI body mass index, SMI skeletal muscle index, GC Gemcitabine Cisplatin, GCb Gemcitabine Carboplatin, MVAC Methotrexate Vinblastine Doxorubicin Cisplatin Prevalence and Timing of Cancer Cachexia At the start of chemotherapy, 45 patients (30%) met the EPCRC criteria for cancer cachexia. During follow-up, the cumulative prevalence increased rapidly: 57.3% developed cachexia within the first 3 months, 74% met the criteria at some point during the observation period (Fig. 1 ). Factors Associated with Cachexia Baseline comparisons revealed that advanced-stage disease and prevalence of sarcopenia was significantly higher in patients with cachexia than in those without (Table 2 ). Table 2 Comparison of clinicopathological characteristics between cachexia and non-cachexia groups Group Non-Cachexia Cachexia p Value Age <73 22 49 0.138 ≥73 16 63 Sex Female 10 27 0.829 Male 28 85 Stage 0 4 2 0.00174 1 2 3 2 17 25 3 9 39 4 6 43 Pathological type Pure UC 30 105 0.0234 Variant 8 7 Radical cystectomy Not performed 21 67 0.704 Performed 17 45 CRP <0.4 mg/dL 20 60 1 ≧0.4 mg/dL 18 52 Sarcopenia(baseline) Sarcopenia 23 96 0.00385 Non-Sarcopenia 14 16 In the multivariate logistic regression analysis, advanced stage (Stage ≥ 3; OR 4.13, 95% CI 1.81–9.43, p = 0.000057) and the presence of sarcopenia (OR 3.16, 95% CI 1.25–7.96, p = 0.015) were identified as independent risk factors for cancer cachexia (Table 3 ). Table 3 Multivariate logistic regression analysis for factors associated with cancer cachexia Factor OR (95% CI) p Value Age ≥ 73 1.51 (0.66–3.47) 0.23 Stage ≥ 3 4.13 (1.81–9.43) 0.00057 Variant pathology 0.33 (0.09–1.1) 0.072 Sarcopenia 3.16 (1.25–7.96) 0.015 The distribution of variant histology differed between the groups, with variant histology being less frequent among patients who developed cachexia (Table 2 , 3 ). Overall Survival Kaplan–Meier analysis revealed significant differences in overall survival (OS) between patients who developed cachexia and those who did not, at all time points within 3 months, 6 months, and 9 months (Fig. 2 a-c). Overall, patients with cachexia at any time had markedly worse outcomes, with a median OS of 827 days (95% CI: 586–1098) from treatment initiation (Fig. 2 d). Prognostic factors Univariate Cox regression identified cachexia, CRP elevation, and advanced stage as potential predictors of OS (Table 4 ). Table 4 Prognostic factors for overall survival using univariate analysis Variable Overall survival Hazard ratio(95%CI) P value Age group, years <73 1 ≧73 1.22(0.78–1.90) 0.39 Sex Female 1 Male 0.84(0.51–1.41) 0.51 Pathological type Pure UC 1 Variant 1.24(0.62–2.48) 0.5489 Stage 0–2 1 3–4 2.32(1.41–3.82) 0.00093 Radical cystectomy Not performed 1 Performed 1.24(0.79–1.93) 0.34 Cachexia Without cachexia 1 With cachexia 2.55(1.46–4.85) 0.0041 C-reactive protein <0.4 mg/dL 1 ≧0.4 mg/dL 2.57(1.64–4.051) 0.000040 In multivariate analysis, two factors remained independently associated with poor survival: Presence of cachexia (HR 2.852, 95% CI 1.41–5.761; p = 0.0034) and CRP > 0.4 mg/dL (HR 3.006, 95% CI 1.83–4.91; p = 0.000011). These findings indicate that both systemic inflammation and metabolic decline contribute significantly to prognosis in patients with bladder cancer. (Table 4 , 5 ). Table 5 Prognostic factors for overall survival using multivariate analysis Factor Hazard ratio(95%CI) P value Age(≥ 73/<73) 1.15(0.73–1.81) 0.54 Stage(≥ 3/ 0.4/≤0.4) 3.006(1.83–4.91) 0.000011 DISCUSSION In this multicenter retrospective study, we found that cancer cachexia, defined by the EPCRC 2011 criteria, was highly prevalent in patients with bladder cancer receiving systemic chemotherapy and that its occurrence was strongly associated with advanced disease stage and inferior overall survival. Cachexia remained independently associated with mortality in multivariate analysis, indicating that this syndrome captures clinically meaningful vulnerability beyond tumor stage alone. Because the EPCRC framework integrates weight loss with BMI and sarcopenia, it operationalizes a syndrome driven by inflammation and catabolism rather than caloric deficit alone [ 1 , 2 , 4 ]. In a population that is often older and comorbid, early identification of this vulnerability may facilitate timely supportive-care referral and realistic shared decision-making. A notable feature of our cohort was the rapid accumulation of cachexia during treatment, with 57% meeting EPCRC criteria within 3 months and 74% during follow-up. This pattern is clinically plausible in advanced urothelial carcinoma, where older age, high tumor burden, and treatment-related anorexia, nausea, dysgeusia, fatigue, and reduced activity can quickly precipitate negative energy balance. Importantly, cancer cachexia is not synonymous with simple weight loss; it reflects an inflammatory and metabolic syndrome characterized by altered energy expenditure, insulin resistance, and catabolic signaling that preferentially depletes skeletal muscle [ 1 , 2 , 4 , 12 ]. Because EPCRC criteria also incorporate sarcopenia, even modest weight changes can qualify as cachexia in patients with low baseline muscle mass, underscoring the importance of body composition assessment in this setting. The early rise in cachexia prevalence in our cohort highlights a narrow window for intervention and reinforces the need for proactive symptom control and nutritional support early in the course of systemic therapy [ 13 – 15 ]. Notably, we observed prognostic separation even when cachexia was assessed early after treatment initiation, underscoring that early-onset cachexia may identify patients with rapidly declining physiologic reserve. This supports close monitoring of weight change, dietary intake, and symptoms during the first treatment cycles, when nausea, dysgeusia, and fatigue are common. Regarding risk factors, advanced stage (stage ≥ III) and baseline sarcopenia were independently associated with cachexia development. The association with stage is biologically coherent because progressive disease is accompanied by escalating inflammatory signaling and metabolic derangements that promote anorexia, lipolysis, and skeletal muscle proteolysis [ 2 , 4 ]. Mechanistically, cytokine-driven pathways including IL-6–JAK/STAT3 signaling [ 16 ] have been implicated in cancer-associated muscle wasting and systemic inflammation [ 2 , 4 ]. Sarcopenia, which was present in a substantial portion of patients at baseline, may reflect both cancer-related catabolism and pre-existing frailty or age-related muscle loss, thereby lowering physiologic reserve and increasing susceptibility to treatment-related stressors. These results support the concept that sarcopenia and cachexia are overlapping but distinct constructs: sarcopenia is a body composition phenotype, whereas cachexia represents an active systemic process characterized by progressive metabolic dysfunction and inflammation [ 1 , 2 , 4 ]. Although sarcopenia is part of the EPCRC definition, our findings highlight that pre-existing low muscle mass and tumor burden together shape cachexia risk. This is consistent with prior bladder cancer literature showing prognostic relevance of sarcopenia and supports using body composition as part of routine baseline assessment [ 8 ]. Our survival analyses further demonstrate that cachexia is prognostically informative in bladder cancer treated with contemporary systemic therapy. The adverse prognostic impact of involuntary weight loss was recognized in early chemotherapy-era studies across malignancies [ 3 ], and later syntheses have highlighted the additional negative prognostic implications of low muscle mass and adverse body composition [ 4 ]. In our cohort, CRP > 0.4 mg/dL was independently associated with mortality, supporting the concept that systemic inflammation is a central driver of both cachexia biology and poor outcomes. Elevated CRP has been incorporated into prognostic tools such as the modified Glasgow Prognostic Score (mGPS), which has been linked to survival in metastatic urothelial carcinoma treated with immune checkpoint inhibitors [ 17 ]. A recent systematic review and meta-analysis in urothelial carcinoma reported that higher pretreatment CRP is consistently associated with worse survival, reinforcing CRP as a clinically accessible marker of adverse systemic inflammation and host vulnerability [ 18 ]. Taken together, these results suggest that combining EPCRC cachexia assessment with simple inflammatory markers may strengthen bedside risk stratification [ 19 ]. Treatment tolerance is an especially relevant implication in advanced bladder cancer, where maintaining treatment delivery and preserving functional status are central goals. Although our dataset did not capture toxicity, dose intensity, or treatment discontinuation, sarcopenia has been linked to poorer outcomes in adults with solid tumors and may be associated with increased chemotherapy toxicity and treatment-related complications [ 20 ]. Because cachexia and sarcopenia often co-occur with inflammation and low functional reserve, early identification may help clinicians anticipate declining performance and consider early supportive measures aimed at stabilizing nutritional status and activity level. In addition, weight loss and reduced muscle mass can impair rehabilitation potential and may worsen patient-reported QOL, further supporting routine assessment as part of comprehensive cancer care [ 13 – 15 ]. In contemporary urothelial carcinoma care, deterioration in nutrition and function can limit treatment delivery and reduce eligibility for subsequent systemic options. Therefore, identifying patients at risk for early cachexia may help prioritize supportive interventions aimed at preserving function and maintaining treatment feasibility. A secondary observation was that variant histology was less frequent among patients who developed cachexia. Given the retrospective design, potential confounding by stage distribution and treatment selection, and the likely small size of histologic subgroups, this finding should be interpreted cautiously and considered hypothesis-generating rather than indicative of a protective biologic effect. Larger prospective datasets with standardized pathologic review and longitudinal nutritional assessment are needed to clarify whether histologic subtype meaningfully modifies cachexia risk. This relationship may be confounded by differences in stage distribution or treatment selection across histologic subtypes and should be interpreted cautiously. From a clinical practice perspective, our results support integrating cachexia screening into routine care for advanced bladder cancer. International guidance emphasizes early identification and multimodal management. ESMO and ASCO recommendations [ 13 , 14 ] highlight systematic screening for weight loss and reduced intake, early referral for nutritional counseling with adequate energy and protein targets, individualized exercise interventions—particularly resistance training when feasible—and aggressive symptom management to improve intake and function [ 13 – 15 ]. In advanced bladder cancer, such an approach may be particularly important given the high early incidence of cachexia and its association with mortality. Furthermore, identification of sarcopenia and inflammation at baseline may help stratify patients for more intensive supportive care and closer monitoring. A pragmatic workflow is to document recent weight history and appetite at baseline, review BMI and CT-derived SMI when available, and consider simple laboratory markers such as CRP. Reassessment during treatment can trigger early dietitian involvement, resistance exercise/rehabilitation referral, and symptom-directed management consistent with guidelines [ 15 ]. This study has several limitations. First, the retrospective design introduces selection bias and limits causal inference. Second, inter-institutional variability in clinical practice and timing of assessments may have influenced the measured incidence and onset of cachexia. Third, EPCRC criteria rely on anthropometrics and CT-derived muscle mass but do not capture functional domains such as muscle strength, physical performance, or patient-reported outcomes, which are increasingly emphasized in modern cachexia frameworks and may provide complementary prognostic information. Fourth, although some patients received newer agents (e.g., immune checkpoint inhibitors and antibody–drug conjugates) in later lines of therapy, treatment exposure was heterogeneous across the cohort. Therefore, cachexia dynamics and their clinical implications may differ by regimen and treatment line, which limits regimen-specific inference. Finally, our cohort was restricted to patients receiving systemic chemotherapy, which may limit generalizability to earlier-stage bladder cancer or patients treated exclusively with surgery. Additionally, follow-up cachexia may be underestimated if patients died before reassessment, which would tend to bias associations toward the null. We also lacked detailed data on treatment discontinuation, adverse events, and functional trajectories, limiting direct inference regarding treatment tolerance. Despite these limitations, our findings demonstrate that EPCRC-defined cachexia is common, occurs early during systemic therapy, and independently portends poor survival in bladder cancer. This underscores the potential clinical value of incorporating standardized cachexia assessment into routine oncologic care, not only as a prognostic marker but also as a trigger for early multimodal supportive interventions. Nevertheless, the consistent and early emergence of cachexia in our cohort highlights the need for prospective studies that integrate longitudinal body composition, functional measures, and inflammatory markers, and that test whether early, guideline-concordant multimodal supportive interventions can improve patient-centered outcomes and treatment feasibility in advanced bladder cancer [ 13 – 15 ]. Prospective studies should incorporate standardized longitudinal assessments of body composition, dietary intake, physical function, and inflammatory markers, and evaluate whether early multimodal supportive care improves quality of life and treatment feasibility in advanced bladder cancer [ 13 – 15 ]. Declarations Acknowledgements The authors would like to thank all the medical staff at Juntendo University Hospital, Juntendo University Nerima Hospital, and Juntendo University Shizuoka Hospital for their support in patient care and data collection. Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Juntendo University (No. E23-0350). Consent to participate Informed consent was obtained from all individual participants included in the study. Conflict of interest The authors declare that they have no conflicts of interest. Data availability The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. References Fearon K, Strasser F, Anker SD et al (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12(5):489–495 Argilés JM, Busquets S, Stemmler B, López-Soriano FJ (2014) Cancer cachexia: understanding the molecular basis. Nat Rev Cancer 14(11):754–762 Dewys WD, Begg C, Lavin PT et al (1980) Prognostic effect of weight loss prior to chemotherapy in cancer patients. Am J Med 69(4):491–497 Baracos VE, Martin L, Korc M, Guttridge DC, Fearon KCH (2018) Cancer-associated cachexia. Nat Rev Dis Primers 4:17105 Bachmann J, Heiligensetzer M, Krakowski-Roosen H et al (2008) Cachexia worsens prognosis in patients with resectable pancreatic cancer. J Gastrointest Surg 12(7):1193–1201 Bozzetti F, Mariani L (2009) Defining and classifying cancer cachexia: a proposal by the SCRINIO Working Group. JPEN J Parenter Enter Nutr 33(4):361–367 Evans WJ, Morley JE, Argilés J et al (2008) Cachexia: a new definition. Clin Nutr 27(6):793–799 Bellos TC, Koutsilieris M, Papatsoris AG (2022) Sarcopenia in urinary bladder cancer: definition, prevalence and prognostic value in survival. Maedica (Bucur) 17(2):427–435 Sun L, Quan XQ, Yu S (2015) An epidemiological survey of cachexia in advanced cancer patients and Analysis on Its Diagnostic and Treatment Status. Nutr Cancer 67(7):1056–1062 Mitsunaga S, Kasamatsu E, Machii K (2020) Incidence and frequency of cancer cachexia during chemotherapy for advanced pancreatic ductal adenocarcinoma. Support Care Cancer 28(11):5271–5279 Prado CM, Lieffers JR, McCargar LJ et al (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9(7):629–635 Directo D, Lee SR (2023) Cancer cachexia: underlying mechanisms and potential therapeutic interventions. Metabolites 13(9):1024 Arends J, Strasser F, Gonella S et al (2021) Cancer cachexia in adult patients: ESMO Clinical Practice Guidelines. ESMO Open 6(3):100092 Roeland EJ, Bohlke K, Baracos VE et al (2020) Management of Cancer Cachexia: ASCO Guideline. J Clin Oncol 38(21):2438–2453 Muscaritoli M, Arends J, Bachmann P et al (2021) ESPEN practical guideline: Clinical Nutrition in cancer. Clin Nutr 40(5):2898–2913 Bonetto A, Aydogdu T, Jin X et al (2012) JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab 303(3):E410–E420 Brown JT, Ou Z, Livingston J et al (2021) Baseline Modified Glasgow Prognostic Score Associated with Survival in Metastatic Urothelial Carcinoma Treated with Immune. Checkp Inhibitors Oncologist 26(5):397–405 Fujiwara Y, Karol AB, Joshi H, Reford E, Izadmehr S, Doroshow DB, Galsky MD (2024) C-reactive protein (CRP) as a prognostic biomarker in patients with urothelial carcinoma: A systematic review and meta-analysis. Crit Rev Oncol Hematol 197:104352 Martin L, Senesse P, Gioulbasanis I et al (2015) Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol 33(1):90–99 Shachar SS, Williams GR, Muss HB, Nishijima TF (2016) Prognostic value of sarcopenia in adults with solid tumours: a meta-analysis and systematic review. Eur J Cancer 57:58–67 Cite Share Download PDF Status: Published Journal Publication published 18 Apr, 2026 Read the published version in International Journal of Clinical Oncology → Version 1 posted Editorial decision: Major revisions 01 Feb, 2026 Reviewers agreed at journal 21 Jan, 2026 Reviewers invited by journal 21 Jan, 2026 Editor assigned by journal 21 Jan, 2026 First submitted to journal 13 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. 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. 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Juntendo Daigaku Igakubu Fuzoku Juntendo Iin","correspondingAuthor":false,"prefix":"","firstName":"Shigeo","middleName":"","lastName":"Horie","suffix":""}],"badges":[],"createdAt":"2026-01-14 09:08:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8599724/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8599724/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10147-026-03043-w","type":"published","date":"2026-04-18T15:59:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":101206501,"identity":"27d090fe-a80b-4b70-b868-32e1ddbfca9b","added_by":"auto","created_at":"2026-01-27 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1","display":"","copyAsset":false,"role":"figure","size":114421,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative Incidence of Cancer Cachexia During Follow-up\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8599724/v1/1b6ca503f79f98bd3240df04.jpg"},{"id":101171039,"identity":"7ae9c471-7e4c-4060-8fe9-1d361ff90644","added_by":"auto","created_at":"2026-01-27 00:06:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":323652,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve for overall survival (OS) according to follow-up cachexia within 3\u003cstrong\u003e (a), \u003c/strong\u003e6 \u003cstrong\u003e(b)\u003c/strong\u003e , 9 \u003cstrong\u003e(c)\u003c/strong\u003e,or 36 \u003cstrong\u003e(d)\u003c/strong\u003e months after the start of chemotherapy.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8599724/v1/065069620421a820a2dc4922.jpg"},{"id":107350933,"identity":"930f86d6-6482-45a5-af55-26950e8fa150","added_by":"auto","created_at":"2026-04-20 16:07:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":864070,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8599724/v1/8294e9e5-74c7-4adf-b245-d9d8f45f0efe.pdf"}],"financialInterests":"","formattedTitle":"Prevalence and Prognostic Impact of Cancer Cachexia in Patients with Bladder Cancer: A Multicenter Retrospective Study","fulltext":[{"header":"INTRODUCTION ","content":"\u003cp\u003eCancer cachexia is defined as \u0026ldquo;a multifactorial syndrome characterized by a loss of skeletal muscle mass that cannot be fully reversed by nutritional support and that leads progressively to functional impairment\u0026rdquo; [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It occurs in 40\u0026ndash;80% of patients with cancer, depending on tumor type [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Cancer cachexia is more common in gastrointestinal and lung cancers [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] but is relatively uncommon in hematological and breast cancers [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. It significantly impacts quality of life (QOL), chemotherapy efficacy, and survival outcomes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], underscoring the need for early intervention and treatment.\u003c/p\u003e \u003cp\u003eDefinitions and diagnostic criteria for cancer cachexia have varied across clinical trials [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In 2011, the European Palliative Care Research Collaborative (EPCRC) established diagnostic criteria for cancer cachexia, which include at least one of the following: (a) weight loss exceeding 5% in the past six months, (b) weight loss exceeding 2% combined with a body mass index (BMI) below 20 kg/m\u0026sup2;, or (c) weight loss exceeding 2% in the presence of sarcopenia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. These criteria are now widely accepted as the consensus standard for diagnosing cancer cachexia.\u003c/p\u003e \u003cp\u003eSarcopenia has been reported as a prognostic factor in bladder cancer [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], however sarcopenia and cachexia represent distinct clinical entities. Cachexia reflects a systemic inflammatory and metabolic state that may have greater clinical impact than muscle mass alone. Despite its relevance, the prevalence and prognostic significance of cancer cachexia in bladder cancer remain insufficiently investigated, even though cachexia is known to adversely affect outcomes in other solid tumors [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven these considerations, we conducted a multicenter retrospective study to evaluate the prevalence, risk factors, and prognostic impac\u003cb\u003et\u003c/b\u003e of cancer cachexia in patients undergoing first-line chemotherapy for bladder cancer, using the standardized EPCRC 2011 criteria. This study aims to clarify the clinical significance of cachexia and provide evidence supporting improved risk stratification and early supportive interventions in this patient population.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS ","content":"\u003cp\u003ePatients\u003c/p\u003e \u003cp\u003e We retrospectively reviewed patients who received first-line chemotherapy for bladder cancer at three institutions: Juntendo Hospital (April 2009\u0026ndash;April 2024), Juntendo Shizuoka Hospital (November 2016\u0026ndash;October 2023), and Juntendo Nerima Hospital (November 2009\u0026ndash;March 2023). Among 227 patients, patients who received only perioperative chemotherapy were excluded, and 150 patients were included in the final analysis.\u003c/p\u003e \u003cp\u003eDefinition of Sarcopenia\u003c/p\u003e \u003cp\u003eA cross-sectional CT image of the third lumbar vertebra (L3) was used to estimate skeletal muscle mass. Muscle cross-sectional area (cm\u0026sup2;) was measured using SYNAPSE VINCENT version 6 (FUJIFILM Medical Systems, Nishiazabu, Minato, Japan). Skeletal Muscle Index (SMI) was calculated using the following equation: L3 SMI (cm\u0026sup2;)/height\u0026sup2; (m\u0026sup2;). Sarcopenia was defined as SMI\u0026thinsp;\u0026lt;\u0026thinsp;55 cm\u0026sup2;/m\u0026sup2; for men and SMI\u0026thinsp;\u0026lt;\u0026thinsp;39 cm\u0026sup2;/m\u0026sup2; for women, as described in a previous study [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDefinition of Cancer Cachexia\u003c/p\u003e \u003cp\u003eCancer cachexia was defined based on the EPCRC criteria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]; weight loss exceeding 5%, or weight loss exceeding 2% with a BMI\u0026thinsp;\u0026lt;\u0026thinsp;20 kg/m\u0026sup2;, or weight loss exceeding 2% accompanied by sarcopenia. Baseline cachexia was defined as meeting the criteria based on weight recorded within 6 months prior to chemotherapy initiation.\u003c/p\u003e \u003cp\u003eThe first time point at which a patient met the EPCRC criteria was considered the onset of follow-up cachexia. Patients who died before the next scheduled assessment were considered not to have reached cachexia onset unless already meeting criteria at their last recorded visit.\u003c/p\u003e \u003cp\u003eData Collection\u003c/p\u003e \u003cp\u003ePatient data were retrospectively collected from medical records. Baseline was defined as the date of chemotherapy initiation. Age, sex, BMI, and blood parameters were recorded at baseline. Changes in chemotherapy regimen during the disease course were recorded.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eTo identify risk factors for cachexia, categorical variables were compared using the Fisher\u0026rsquo;s exact test and multivariate logistic regression analysis was used for furthermore evaluation. Overall survival (OS) was defined as the duration from the first chemotherapy dose to death from any cause. Survival analysis was conducted using the Kaplan-Meier method and log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Factors identified in univariate analysis were further examined using multivariate Cox regression with the enter method to identify independent predictors of OS. Statistical analysis was performed using EZR software. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS ","content":"\u003cp\u003ePatient Characteristics\u003c/p\u003e \u003cp\u003eA total of 150 patients met the eligibility criteria for this study. The cohort consisted of 113 men (75%) and 37 women (25%). Twenty-seven patients (18%) had concurrent upper urinary tract carcinoma (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Baseline TNM classification was as follows: T stage: T0, 17 (11.3%); T1, 8 (5.3%); T2, 75 (50.0%); T3, 34 (22.7%); T4, 16 (10.7%), N stage: N0, 98 (65.3%); N1, 10 (6.7%); N2, 34 (22.7%); N3, 8 (5.3%), M stage: M0, 101 (67.3%); M1, 49 (32.7%). Overall, 64.7% of patients had stage III or IV disease at treatment initiation. Median age was 73 years [IQR, 65\u0026ndash;78), and the median BMI was 22.6 kg/m\u0026sup2; [IQR, 20.0\u0026ndash;24.8]. 36 patients (24%) had organ metastases at baseline. Chemotherapy regimens administered at any time included: GC 86 (57%), GCb 77 (51.3%), Gemcitabine monotherapy 4 (2.7%), MVAC 9 (6%), Avelumab 9 (6%), Pembrolizumab 43 (28.7%), Enfortumab vedotin 13 (8.7%), Nivolumab 2 (1.3%), and 8 others (5.3%). A total of 62 patients (41.3%) underwent radical cystectomy. Median SMI was 43.09 cm\u0026sup2;/m\u0026sup2; [IQR, 37.37\u0026ndash;47.48] and 119 patients (79.3%) met the criteria for sarcopenia from the start of chemotherapy.\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\u003e Patient characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[65\u0026ndash;78]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \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\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(75%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(25%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e 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align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(22.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(10.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(65.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(6.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(22.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(5.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(67.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(32.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0is\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(4.0%)\u003c/p\u003e \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\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(3.3%)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(28.0%)\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\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(32.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eⅣ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(32.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisceral metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(24%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eupper ureteral carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecombined\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCystectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(41.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(57%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(51.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGemcitabine monotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(2.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMVAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAvelumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePembrolizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(28.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnfortumab vedotin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(8.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNivolumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(1.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eother\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(5.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emultiple chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(44.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[10.8\u0026ndash;13.6]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[3.6\u0026ndash;4.2]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[0.75\u0026ndash;1.13]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR (mL/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[43.88\u0026ndash;75.33]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[0.1\u0026ndash;1.34]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCachexia(baseline)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(30%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSarcopenia(baseline)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(79.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSMI(cm\u003csup\u003e2\u003c/sup\u003e/m\u003csup\u003e2\u003c/sup\u003e)(baseline)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[37.37\u0026ndash;47.48]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eValues are number (percent) of patients or median [IQR]\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eBMI body mass index, SMI skeletal muscle index, GC Gemcitabine Cisplatin, GCb Gemcitabine Carboplatin, MVAC Methotrexate Vinblastine Doxorubicin Cisplatin\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePrevalence and Timing of Cancer Cachexia\u003c/p\u003e \u003cp\u003eAt the start of chemotherapy, 45 patients (30%) met the EPCRC criteria for cancer cachexia. During follow-up, the cumulative prevalence increased rapidly: 57.3% developed cachexia within the first 3 months, 74% met the criteria at some point during the observation period (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFactors Associated with Cachexia\u003c/p\u003e \u003cp\u003eBaseline comparisons revealed that advanced-stage disease and prevalence of sarcopenia was significantly higher in patients with cachexia than in those without (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e Comparison of clinicopathological characteristics between cachexia and non-cachexia groups\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-Cachexia\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCachexia\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\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\u003e\u0026lt;73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.138\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e63\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\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \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\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.829\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\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e85\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\u003eStage\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\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00174\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25\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\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e39\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\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43\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\u003ePathological type\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\u003ePure UC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0234\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\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\u003eRadical cystectomy\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\u003eNot performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.704\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerformed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45\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\u003eCRP\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\u003e\u0026lt;0.4 mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e≧0.4 mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52\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\u003eSarcopenia(baseline)\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\u003eSarcopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00385\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Sarcopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the multivariate logistic regression analysis, advanced stage (Stage\u0026thinsp;\u0026ge;\u0026thinsp;3; OR 4.13, 95% CI 1.81\u0026ndash;9.43, p\u0026thinsp;=\u0026thinsp;0.000057) and the presence of sarcopenia (OR 3.16, 95% CI 1.25\u0026ndash;7.96, p\u0026thinsp;=\u0026thinsp;0.015) were identified as independent risk factors for cancer cachexia (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e Multivariate logistic regression analysis for factors associated with cancer cachexia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.51 (0.66\u0026ndash;3.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.13 (1.81\u0026ndash;9.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariant pathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.33 (0.09\u0026ndash;1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSarcopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.16 (1.25\u0026ndash;7.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe distribution of variant histology differed between the groups, with variant histology being less frequent among patients who developed cachexia (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e,\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOverall Survival\u003c/p\u003e \u003cp\u003eKaplan\u0026ndash;Meier analysis revealed significant differences in overall survival (OS) between patients who developed cachexia and those who did not, at all time points within 3 months, 6 months, and 9 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea-c).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOverall, patients with cachexia at any time had markedly worse outcomes, with a median OS of 827 days (95% CI: 586\u0026ndash;1098) from treatment initiation (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed).\u003c/p\u003e \u003cp\u003ePrognostic factors\u003c/p\u003e \u003cp\u003eUnivariate Cox regression identified cachexia, CRP elevation, and advanced stage as potential predictors of OS (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrognostic factors for overall survival using univariate analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall survival\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHazard ratio(95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge group, years\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e≧73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.22(0.78\u0026ndash;1.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \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\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\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\u003e0.84(0.51\u0026ndash;1.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological type\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePure UC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.24(0.62\u0026ndash;2.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5489\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.32(1.41\u0026ndash;3.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadical cystectomy\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerformed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.24(0.79\u0026ndash;1.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCachexia\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWithout cachexia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWith cachexia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.55(1.46\u0026ndash;4.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-reactive protein\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;0.4 mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e≧0.4 mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.57(1.64\u0026ndash;4.051)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000040\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\u003eIn multivariate analysis, two factors remained independently associated with poor survival: Presence of cachexia (HR 2.852, 95% CI 1.41\u0026ndash;5.761; p\u0026thinsp;=\u0026thinsp;0.0034) and CRP\u0026thinsp;\u0026gt;\u0026thinsp;0.4 mg/dL (HR 3.006, 95% CI 1.83\u0026ndash;4.91; p\u0026thinsp;=\u0026thinsp;0.000011). These findings indicate that both systemic inflammation and metabolic decline contribute significantly to prognosis in patients with bladder cancer. (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e,\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrognostic factors for overall survival using multivariate analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHazard ratio(95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(\u0026ge;\u0026thinsp;73/\u0026lt;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.15(0.73\u0026ndash;1.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage(\u0026ge;\u0026thinsp;3/\u0026lt;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.53(0.89\u0026ndash;2.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCachexia(with/without)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.852(1.41\u0026ndash;5.761)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.0034\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP(\u0026gt;\u0026thinsp;0.4/\u0026le;0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.006(1.83\u0026ndash;4.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.000011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"DISCUSSION ","content":"\u003cp\u003eIn this multicenter retrospective study, we found that cancer cachexia, defined by the EPCRC 2011 criteria, was highly prevalent in patients with bladder cancer receiving systemic chemotherapy and that its occurrence was strongly associated with advanced disease stage and inferior overall survival. Cachexia remained independently associated with mortality in multivariate analysis, indicating that this syndrome captures clinically meaningful vulnerability beyond tumor stage alone. Because the EPCRC framework integrates weight loss with BMI and sarcopenia, it operationalizes a syndrome driven by inflammation and catabolism rather than caloric deficit alone [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In a population that is often older and comorbid, early identification of this vulnerability may facilitate timely supportive-care referral and realistic shared decision-making.\u003c/p\u003e \u003cp\u003eA notable feature of our cohort was the rapid accumulation of cachexia during treatment, with 57% meeting EPCRC criteria within 3 months and 74% during follow-up. This pattern is clinically plausible in advanced urothelial carcinoma, where older age, high tumor burden, and treatment-related anorexia, nausea, dysgeusia, fatigue, and reduced activity can quickly precipitate negative energy balance. Importantly, cancer cachexia is not synonymous with simple weight loss; it reflects an inflammatory and metabolic syndrome characterized by altered energy expenditure, insulin resistance, and catabolic signaling that preferentially depletes skeletal muscle [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Because EPCRC criteria also incorporate sarcopenia, even modest weight changes can qualify as cachexia in patients with low baseline muscle mass, underscoring the importance of body composition assessment in this setting. The early rise in cachexia prevalence in our cohort highlights a narrow window for intervention and reinforces the need for proactive symptom control and nutritional support early in the course of systemic therapy [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Notably, we observed prognostic separation even when cachexia was assessed early after treatment initiation, underscoring that early-onset cachexia may identify patients with rapidly declining physiologic reserve. This supports close monitoring of weight change, dietary intake, and symptoms during the first treatment cycles, when nausea, dysgeusia, and fatigue are common.\u003c/p\u003e \u003cp\u003eRegarding risk factors, advanced stage (stage\u0026thinsp;\u0026ge;\u0026thinsp;III) and baseline sarcopenia were independently associated with cachexia development. The association with stage is biologically coherent because progressive disease is accompanied by escalating inflammatory signaling and metabolic derangements that promote anorexia, lipolysis, and skeletal muscle proteolysis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Mechanistically, cytokine-driven pathways including IL-6\u0026ndash;JAK/STAT3 signaling [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] have been implicated in cancer-associated muscle wasting and systemic inflammation [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Sarcopenia, which was present in a substantial portion of patients at baseline, may reflect both cancer-related catabolism and pre-existing frailty or age-related muscle loss, thereby lowering physiologic reserve and increasing susceptibility to treatment-related stressors. These results support the concept that sarcopenia and cachexia are overlapping but distinct constructs: sarcopenia is a body composition phenotype, whereas cachexia represents an active systemic process characterized by progressive metabolic dysfunction and inflammation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Although sarcopenia is part of the EPCRC definition, our findings highlight that pre-existing low muscle mass and tumor burden together shape cachexia risk. This is consistent with prior bladder cancer literature showing prognostic relevance of sarcopenia and supports using body composition as part of routine baseline assessment [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur survival analyses further demonstrate that cachexia is prognostically informative in bladder cancer treated with contemporary systemic therapy. The adverse prognostic impact of involuntary weight loss was recognized in early chemotherapy-era studies across malignancies [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], and later syntheses have highlighted the additional negative prognostic implications of low muscle mass and adverse body composition [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In our cohort, CRP\u0026thinsp;\u0026gt;\u0026thinsp;0.4 mg/dL was independently associated with mortality, supporting the concept that systemic inflammation is a central driver of both cachexia biology and poor outcomes. Elevated CRP has been incorporated into prognostic tools such as the modified Glasgow Prognostic Score (mGPS), which has been linked to survival in metastatic urothelial carcinoma treated with immune checkpoint inhibitors [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A recent systematic review and meta-analysis in urothelial carcinoma reported that higher pretreatment CRP is consistently associated with worse survival, reinforcing CRP as a clinically accessible marker of adverse systemic inflammation and host vulnerability [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Taken together, these results suggest that combining EPCRC cachexia assessment with simple inflammatory markers may strengthen bedside risk stratification [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTreatment tolerance is an especially relevant implication in advanced bladder cancer, where maintaining treatment delivery and preserving functional status are central goals. Although our dataset did not capture toxicity, dose intensity, or treatment discontinuation, sarcopenia has been linked to poorer outcomes in adults with solid tumors and may be associated with increased chemotherapy toxicity and treatment-related complications [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Because cachexia and sarcopenia often co-occur with inflammation and low functional reserve, early identification may help clinicians anticipate declining performance and consider early supportive measures aimed at stabilizing nutritional status and activity level. In addition, weight loss and reduced muscle mass can impair rehabilitation potential and may worsen patient-reported QOL, further supporting routine assessment as part of comprehensive cancer care [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In contemporary urothelial carcinoma care, deterioration in nutrition and function can limit treatment delivery and reduce eligibility for subsequent systemic options. Therefore, identifying patients at risk for early cachexia may help prioritize supportive interventions aimed at preserving function and maintaining treatment feasibility.\u003c/p\u003e \u003cp\u003eA secondary observation was that variant histology was less frequent among patients who developed cachexia. Given the retrospective design, potential confounding by stage distribution and treatment selection, and the likely small size of histologic subgroups, this finding should be interpreted cautiously and considered hypothesis-generating rather than indicative of a protective biologic effect. Larger prospective datasets with standardized pathologic review and longitudinal nutritional assessment are needed to clarify whether histologic subtype meaningfully modifies cachexia risk. This relationship may be confounded by differences in stage distribution or treatment selection across histologic subtypes and should be interpreted cautiously.\u003c/p\u003e \u003cp\u003eFrom a clinical practice perspective, our results support integrating cachexia screening into routine care for advanced bladder cancer. International guidance emphasizes early identification and multimodal management. ESMO and ASCO recommendations [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] highlight systematic screening for weight loss and reduced intake, early referral for nutritional counseling with adequate energy and protein targets, individualized exercise interventions\u0026mdash;particularly resistance training when feasible\u0026mdash;and aggressive symptom management to improve intake and function [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In advanced bladder cancer, such an approach may be particularly important given the high early incidence of cachexia and its association with mortality. Furthermore, identification of sarcopenia and inflammation at baseline may help stratify patients for more intensive supportive care and closer monitoring. A pragmatic workflow is to document recent weight history and appetite at baseline, review BMI and CT-derived SMI when available, and consider simple laboratory markers such as CRP. Reassessment during treatment can trigger early dietitian involvement, resistance exercise/rehabilitation referral, and symptom-directed management consistent with guidelines [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, the retrospective design introduces selection bias and limits causal inference. Second, inter-institutional variability in clinical practice and timing of assessments may have influenced the measured incidence and onset of cachexia. Third, EPCRC criteria rely on anthropometrics and CT-derived muscle mass but do not capture functional domains such as muscle strength, physical performance, or patient-reported outcomes, which are increasingly emphasized in modern cachexia frameworks and may provide complementary prognostic information. Fourth, although some patients received newer agents (e.g., immune checkpoint inhibitors and antibody\u0026ndash;drug conjugates) in later lines of therapy, treatment exposure was heterogeneous across the cohort. Therefore, cachexia dynamics and their clinical implications may differ by regimen and treatment line, which limits regimen-specific inference. Finally, our cohort was restricted to patients receiving systemic chemotherapy, which may limit generalizability to earlier-stage bladder cancer or patients treated exclusively with surgery. Additionally, follow-up cachexia may be underestimated if patients died before reassessment, which would tend to bias associations toward the null. We also lacked detailed data on treatment discontinuation, adverse events, and functional trajectories, limiting direct inference regarding treatment tolerance.\u003c/p\u003e \u003cp\u003eDespite these limitations, our findings demonstrate that EPCRC-defined cachexia is common, occurs early during systemic therapy, and independently portends poor survival in bladder cancer. This underscores the potential clinical value of incorporating standardized cachexia assessment into routine oncologic care, not only as a prognostic marker but also as a trigger for early multimodal supportive interventions. Nevertheless, the consistent and early emergence of cachexia in our cohort highlights the need for prospective studies that integrate longitudinal body composition, functional measures, and inflammatory markers, and that test whether early, guideline-concordant multimodal supportive interventions can improve patient-centered outcomes and treatment feasibility in advanced bladder cancer [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Prospective studies should incorporate standardized longitudinal assessments of body composition, dietary intake, physical function, and inflammatory markers, and evaluate whether early multimodal supportive care improves quality of life and treatment feasibility in advanced bladder cancer [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003e The authors would like to thank all the medical staff at Juntendo University Hospital, Juntendo University Nerima Hospital, and Juntendo University Shizuoka Hospital for their support in patient care and data collection.\u003c/p\u003e \u003cp\u003eEthics approval\u003c/p\u003e \u003cp\u003e This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Juntendo University (No. E23-0350).\u003c/p\u003e \u003cp\u003eConsent to participate\u003c/p\u003e \u003cp\u003e Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e \u003cp\u003eConflict of interest\u003c/p\u003e \u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFearon K, Strasser F, Anker SD et al (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12(5):489\u0026ndash;495\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArgil\u0026eacute;s JM, Busquets S, Stemmler B, L\u0026oacute;pez-Soriano FJ (2014) Cancer cachexia: understanding the molecular basis. Nat Rev Cancer 14(11):754\u0026ndash;762\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDewys WD, Begg C, Lavin PT et al (1980) Prognostic effect of weight loss prior to chemotherapy in cancer patients. Am J Med 69(4):491\u0026ndash;497\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaracos VE, Martin L, Korc M, Guttridge DC, Fearon KCH (2018) Cancer-associated cachexia. Nat Rev Dis Primers 4:17105\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBachmann J, Heiligensetzer M, Krakowski-Roosen H et al (2008) Cachexia worsens prognosis in patients with resectable pancreatic cancer. J Gastrointest Surg 12(7):1193\u0026ndash;1201\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBozzetti F, Mariani L (2009) Defining and classifying cancer cachexia: a proposal by the SCRINIO Working Group. JPEN J Parenter Enter Nutr 33(4):361\u0026ndash;367\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEvans WJ, Morley JE, Argil\u0026eacute;s J et al (2008) Cachexia: a new definition. Clin Nutr 27(6):793\u0026ndash;799\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBellos TC, Koutsilieris M, Papatsoris AG (2022) Sarcopenia in urinary bladder cancer: definition, prevalence and prognostic value in survival. Maedica (Bucur) 17(2):427\u0026ndash;435\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun L, Quan XQ, Yu S (2015) An epidemiological survey of cachexia in advanced cancer patients and Analysis on Its Diagnostic and Treatment Status. Nutr Cancer 67(7):1056\u0026ndash;1062\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitsunaga S, Kasamatsu E, Machii K (2020) Incidence and frequency of cancer cachexia during chemotherapy for advanced pancreatic ductal adenocarcinoma. Support Care Cancer 28(11):5271\u0026ndash;5279\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrado CM, Lieffers JR, McCargar LJ et al (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9(7):629\u0026ndash;635\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDirecto D, Lee SR (2023) Cancer cachexia: underlying mechanisms and potential therapeutic interventions. Metabolites 13(9):1024\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArends J, Strasser F, Gonella S et al (2021) Cancer cachexia in adult patients: ESMO Clinical Practice Guidelines. ESMO Open 6(3):100092\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoeland EJ, Bohlke K, Baracos VE et al (2020) Management of Cancer Cachexia: ASCO Guideline. J Clin Oncol 38(21):2438\u0026ndash;2453\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMuscaritoli M, Arends J, Bachmann P et al (2021) ESPEN practical guideline: Clinical Nutrition in cancer. Clin Nutr 40(5):2898\u0026ndash;2913\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBonetto A, Aydogdu T, Jin X et al (2012) JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab 303(3):E410\u0026ndash;E420\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown JT, Ou Z, Livingston J et al (2021) Baseline Modified Glasgow Prognostic Score Associated with Survival in Metastatic Urothelial Carcinoma Treated with Immune. Checkp Inhibitors Oncologist 26(5):397\u0026ndash;405\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFujiwara Y, Karol AB, Joshi H, Reford E, Izadmehr S, Doroshow DB, Galsky MD (2024) C-reactive protein (CRP) as a prognostic biomarker in patients with urothelial carcinoma: A systematic review and meta-analysis. Crit Rev Oncol Hematol 197:104352\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartin L, Senesse P, Gioulbasanis I et al (2015) Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol 33(1):90\u0026ndash;99\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShachar SS, Williams GR, Muss HB, Nishijima TF (2016) Prognostic value of sarcopenia in adults with solid tumours: a meta-analysis and systematic review. Eur J Cancer 57:58\u0026ndash;67\u003c/span\u003e\u003c/li\u003e\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":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"bladder cancer, cancer cachexia, sarcopenia, skeletal muscle index, chemotherapy","lastPublishedDoi":"10.21203/rs.3.rs-8599724/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8599724/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCancer cachexia is a multifactorial syndrome characterized by progressive skeletal muscle loss and systemic inflammation. Although sarcopenia has been reported as a prognostic factor in bladder cancer, the prevalence and prognostic significance of cancer cachexia defined by standardized criteria remain unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed patients who received first-line systemic chemotherapy for urothelial carcinoma at three institutions. Cancer cachexia was defined according to the 2011 European Palliative Care Research Collaborative (EPCRC) criteria based on weight loss, body mass index, and CT-derived L3 skeletal muscle index. Baseline cachexia was assessed within 6 months prior to treatment initiation, and follow-up cachexia was evaluated during treatment. Survival outcomes and prognostic factors were analyzed using Kaplan\u0026ndash;Meier methods, logistic regression, and Cox proportional hazards models.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 150 eligible patients, 30% met the criteria for cachexia at treatment initiation. The cumulative prevalence increased to 57.3% within 3 months and reached 74% at some point during the observation period. Cachexia was significantly associated with advanced disease stage and sarcopenia. Overall survival was significantly shorter in patients who developed cachexia, with a median survival of 827 days (95% confidence interval 586\u0026ndash;1098). Multivariate Cox analysis identified cancer cachexia and elevated C-reactive protein (CRP) (\u0026gt;\u0026thinsp;0.4 mg/dL) as independent predictors of poor overall survival.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCancer cachexia is highly prevalent in patients with bladder cancer receiving first-line chemotherapy and is independently associated with reduced survival. Early identification of metabolic deterioration may improve risk stratification and guide supportive interventions.\u003c/p\u003e","manuscriptTitle":"Prevalence and Prognostic Impact of Cancer Cachexia in Patients with Bladder Cancer: A Multicenter Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-27 00:06:49","doi":"10.21203/rs.3.rs-8599724/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revisions","date":"2026-02-01T18:55:43+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2026-01-22T00:16:20+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-22T00:09:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-21T07:36:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Oncology","date":"2026-01-14T04:07:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"25088653-f064-4e51-8c96-38211e54ff08","owner":[],"postedDate":"January 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-20T16:04:44+00:00","versionOfRecord":{"articleIdentity":"rs-8599724","link":"https://doi.org/10.1007/s10147-026-03043-w","journal":{"identity":"international-journal-of-clinical-oncology","isVorOnly":false,"title":"International Journal of Clinical Oncology"},"publishedOn":"2026-04-18 15:59:03","publishedOnDateReadable":"April 18th, 2026"},"versionCreatedAt":"2026-01-27 00:06:49","video":"","vorDoi":"10.1007/s10147-026-03043-w","vorDoiUrl":"https://doi.org/10.1007/s10147-026-03043-w","workflowStages":[]},"version":"v1","identity":"rs-8599724","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8599724","identity":"rs-8599724","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}