Predictive risk factors of bladder recurrence after radical nephroureterectomy for non-metastatic upper tract urothelial carcinoma

Predictive risk factors of bladder recurrence after radical nephroureterectomy for non-metastatic upper tract urothelial carcinoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Predictive risk factors of bladder recurrence after radical nephroureterectomy for non-metastatic upper tract urothelial carcinoma Yi-Chung Chen, Ting-Shuo Kang, Hung-Jen Shih, Jiun-Yi Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6422108/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background The aim of our study was to explore predictive factors for bladder recurrence and oncologic outcomes in patients with non-metastatic upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy with bladder cuff excision (RNUx). Methods The retrospective cohort study enrolled 169 patients after RNUx in Changhua Christian Hospital between January 2010 and October 2023. Patients were divided into two groups of either experience bladder recurrence (n = 44) or not (n = 125). Data on clinical parameters, pre-surgery ureteroscopy, pre-surgery hydronephrosis, pathologic features, comorbidities, smoking, adjuvant chemotherapy, and intravesical chemotherapy were collected from patients’ medical records. The log-rank test and multivariable Cox regression analysis were performed to identify variables associated with bladder recurrence-free survival (BRFS), distant metastasis-free survival (DMFS), and overall survival (OS). Results Our finding shows that the BRFS rate was 81.8% at 12 months and 69.6% at 36 months after RNUx. Cox regression models revealed that male (aHR: 0.41 for females, 95% CI: 0.21–0.78, p = 0.007), carcinoma in situ (aHR: 2.62, 95% CI: 1.07–6.41, p = 0.035) and hypertension (aHR:2.25, 95% CI: 1.13–4.49, p = 0.022) were risk factors of bladder recurrence. Furthermore, advanced stage and lymphovascular invasion were identified as risk factors of DMFS, and advanced T stage and hemodialysis were associated with poorer OS. Conclusion Our study identified several significant risk factors of bladder recurrence, distant metastasis, and all-cause death. These findings provide a reference of clinical care. A more frequent surveillance schedule may be helpful for these patients. upper tract urothelial carcinoma bladder recurrence radical nephroureterectomy Figures Figure 1 Figure 2 Figure 3 Introduction Urothelial carcinoma is the sixth most frequent type of cancer in United States. While bladder urothelial carcinoma accounts for 90–95% of cases, upper urinary tract urothelial carcinoma (UTUC) is relatively rare, comprising only 5–10% of all urothelial carcinomas.( 1 ) Raman et al. reported a rise in the incidence of UTUC in the United States, increasing from 1.88 to 2.06 cases per 100,000 population.( 2 ) In contrast, Taiwan has reported an abnormally high incidence of UTUC, with a rate of 4 per 100,000, accounting for up to 30% of all urinary tract cancers.( 3 ) Radical nephroureterectomy with bladder cuff resection (RNUx) is the standard method for non-metastatic UTUC. Various surgical methods of bladder cuff resection have been employed, including extravesical, intravesical, and transurethral approaches. However, there is still no consensus regarding oncological outcomes in current guidelines. ( 4 , 5 ) The oncologic outcome is associated with the stage and pathologic features of UTUC, and decisions regarding adjuvant chemotherapy after surgery generally depend on these factors. Additionally, the European Association of Urology (EAU) guidelines recommend a single post-operative intravesical chemotherapy following RNUx to reduce the risk of bladder recurrence. ( 6 ) Due to the ability of urothelial carcinoma cells to proliferate through urine and seed across the urinary system, the risk of bladder recurrence after surgery cannot be ignored. Bladder recurrence following RNUx has poorer oncological outcomes and increased medical costs. The incidence of bladder recurrence after surgery ranges from 33–70% in the residual ureteral stump. ( 7 ) Moreover, predicting which patients will develop bladder recurrence remains challenging. Several risk factors have been linked to bladder recurrence, including multiple tumor foci, incomplete surgery, sex, age, lymphovascular invasion, tumor grade, and T stage. ( 8 , 9 ) Furthermore, ureteral tumors have been associated with worse oncologic outcomes compared to renal pelvis tumors. ( 10 ) Despite previous investigations, the risk factors of bladder recurrence are not yet fully understood and remain a subject of debate. Several studies have identified a history of concurrent or prior bladder cancer as a significant risk factor of bladder recurrence following RNUx. ( 11 – 14 ) Unlike these studies, this present study aimed to identify predictive factors for bladder recurrence and oncologic outcomes in patients with non-metastatic UTUC undergoing RNUx, focusing exclusively on those without concurrent or prior bladder cancer to minimize effects of confounding factors. Methods The present study was approved by the review board of our institution (CCH IRB No.231226). Patients who underwent RNUx from January 2010 to October 2023 in the Changhua Christian Hospital were retrospectively reviewed. All the operations were performed by ten experienced surgeons. Patients who had a pathological diagnosis of urothelial carcinoma of the renal pelvis or ureter and pathological staging of T1-3N0 were included. However, patients with bilateral UTUC, non-urothelial carcinoma of the ureter or the renal pelvis, other primary cancers, pathological staging of T4 or N1-3, concurrent bladder cancer, history of bladder cancer, previous endoscopic laser ablation of ureter or renal pelvis tumor history, or incomplete information were excluded. Patients were divided into two groups according to their bladder recurrence status after the operation. Data on patient medical records and clinical parameters were retrieved, including sex, age, pre-surgery ureteroscopy(URS), pre-surgery hydronephrosis, surgical method, tumor site, tumor location, clinical T stage, pathologic T stage, carcinoma in situ, surgical margin, lympho-vascular invasion, comorbidities (hypertension, diabetes mellitus, chronic kidney disease and hemodialysis status), smoking, adjuvant chemotherapy, intravesical chemotherapy, oncologic outcome (bladder recurrence and distant metastasis), mortality, and follow-up period. Hypertension, diabetes mellitus, chronic kidney disease, and hemodialysis were referred to ICD-9-CM codes used in the hospital. Tumor stage was evaluated according to the 2002 American Joint Committee Cancer TNM system. Tumor grade was reviewed by two pathologists and classified as low or high-grade using the 2004 World Health Organization grading system. After the operation, patients were followed up according to National Comprehensive Cancer Network guidelines and outpatient clinic visits were arranged every 3 months every year. Bladder recurrence was defined based on the pathological report following transurethral biopsy of a bladder tumor during follow-up cystoscopy. If clinically indicated, computed tomography or magnetic resonance imaging were performed and distant metastasis was defined based on the radiological report such as lymph node metastasis or distant metastasis. Adjuvant chemotherapy and intravesical chemotherapy were administered to 26 and 10 patients, respectively, according to pathological stage and consent to treatment. All data analyses were conducted using IBM SPSS (version 22.0). Demographic and clinicopathologic characteristics were compared between the bladder recurrence and non-bladder recurrence groups using the chi-square test, or Fisher’s exact test when expected counts were small. The log-rank test and multivariable Cox regression analysis were performed to evaluate the associations between variables and bladder recurrence-free survival (BRFS), distant metastasis-free survival (DMFS), and overall survival (OS). Variables with p < 0.15 from the log-rank test were included in the multivariable Cox regression models. Variables meeting this criterion but having no events in one of the categories were excluded from the Cox model due to unstable estimation of adjusted hazard ratios. A two-sided p-value of < 0.05 was considered statistically significant for all hypothesis tests. Results Initially, 353 patients who underwent RNUx were reviewed. Among them, 184 patients were excluded due to bilateral UTUC (n = 1), non-urothelial carcinoma of the ureter or the renal pelvis (n = 27), other primary cancer (n = 35), concurrent bladder cancer or bladder cancer history (n = 52), pathological staging of T4 or N1-3 (n = 21), previous endoscopic laser ablation of ureter or renal pelvis tumor history (n = 3), and incomplete information (n = 45). As a result, 169 patients were eligible for analysis with an average followed-up period of 41.7 ± 34.5 months (ranging from 0.4 to 138.2 months, IQR:51.8 months). The bladder cuff was managed via a transurethral approach in 151 cases (89.3%) or an extravesical approach in 18 cases (10.7%). During the follow-up period, 44 patients (26%) had bladder recurrence who were then categorized into the bladder recurrence group, while the remaining 125 patients (74%) were categorized into the non-bladder recurrence group. Patients’ demographics and clinicopathologic characteristics were shown in Table 1 . Table 1 Demographics and clinicopathologic characteristics of 169 patients Variable Category Total (n = 169) Bladder recurrence p-value No (n = 125) Yes (n = 44) Sex Male 70 43 27 0.002 Female 99 82 17 Age group < 70 years 88 61 27 0.151 ≥ 70 years 81 64 17 Pre-surgery URS yes 142 105 37 0.989 no 27 20 7 Surgical method Open 34 21 13 0.070 Laparoscope /Robotic-assisted 135 104 31 Tumor site Left 88 64 24 0.702 Right 81 61 20 Tumor location Renal Pelvis 115 88 27 0.557 a Upper 15 11 4 Middle 19 14 5 Lower 17 10 7 More than one site 3 2 1 Tumor grade High 155 115 40 1.000 a Low 14 10 4 cT stage cT1 39 28 12 0.650 cT2 70 51 19 cT3 59 46 13 pT stage pTis 2 2 0 0.306 a pTa 24 17 7 pT1 46 32 14 pT2 31 20 11 pT3 66 54 12 Carcinoma in situ Yes 49 11 38 0.387 a No 120 114 6 Surgical margin Yes 3 1 2 0.166 a No 166 124 42 Lympho-vascular invasion Yes 55 40 15 0.799 No 114 85 29 Hydronephrosis Yes 87 64 23 0.903 No 82 61 21 Hypertension Yes 106 75 31 0.217 No 63 50 13 Diabetes mellitus Yes 65 47 18 0.698 No 104 78 26 Chronic kidney disease Yes 118 87 31 0.915 No 51 38 13 Hemodialysis Yes 16 12 4 1.000 a No 153 113 40 Smoking Yes 18 10 8 0.085 a No 151 115 36 Intravesical chemotherapy Yes 10 9 1 0.457 a No 159 116 43 Adjuvant chemotherapy Yes 26 22 4 0.199 No 143 103 40 a Fisher’s exact test due to small expected counts In general, the BRFS rate was 81.8% at 12 months after RNUx, 69.6% at 36 months after RNUx, and 66.6% at 60 months after RNUx. Results from log-rank tests revealed some associated factors of bladder recurrence, including male (p < 0.001), smoking (p = 0.023), and tumor location in the lower ureter (p = 0.046). Multivariate Cox regression models showed that male (adjusted Hazard Ration [aHR]: 0.41 for females vs. males, 95% Confidence Interval: 0.21–0.78, p = 0.007), carcinoma in situ (aHR: 2.62, 1.07–6.41, p = 0.035) (Fig. 1 ), and hypertension (aHR: 2.25, 1.13–4.49, p = 0.022) were related to worse bladder recurrence rate. (Table 2 ) Table 2 Cox regression analyses predicting bladder recurrence free survival, distant metastasis free survival and overall survival Bladder recurrence free survival Distant metastasis free survival Overall survival Cox regression Cox regression Cox regression p-value of LR test aHR Lower limit Upper limit p-value p-value of LR test aHR Lower limit Upper limit p-value p-value of LR test aHR Lower limit Upper limit p-value Sex (male vs. female) < 0.001 0.41 0.21 0.78 0.007 0.781 0.596 Age (≥ 70 vs. <70) 0.405 0.654 0.150 Pre-surgery URS (yes vs. no) 0.924 0.746 0.480 OP method (open vs. laparoscope/robotic-assisted) 0.263 0.434 0.672 Tumor site (left vs. right) 0.986 0.078 1.32 0.60 2.91 0.487 0.162 Tumor grade (high vs. low) 0.815 0.081 0.117 pT stage (≥ pT2 vs.<pT2) 0.624 < 0.001 7.45 1.65 33.60 0.009 < 0.001 4.71 1.30 17.07 0.018 Carcinoma in situ (yes vs. no) 0.132 2.62 1.07 6.41 0.035 0.779 0.751 Surgical margin (yes vs. no) 0.071 2.67 0.44 16.16 0.285 0.484 0.013 2.65 0.39 17.87 0.318 Lympho-vascular invasion (yes vs. no) 0.405 < 0.001 2.82 1.26 6.27 0.011 0.002 2.93 1.18 7.26 0.021 Hydronephrosis (yes vs. no) 0.710 0.484 0.709 Hypertension (yes vs. no) 0.067 2.25 1.13 4.49 0.022 0.644 0.358 Diabetes mellitus (yes vs. no) 0.680 0.988 0.897 Chronic kidney disease (yes vs. no) 0.894 0.848 0.051 2.46 0.67 9.01 0.172 Hemodialysis (yes vs. no) 0.820 0.334 0.076 3.52 1.10 11.24 0.033 Smoking (yes vs. no) 0.023 1.59 0.66 3.84 0.301 0.598 0.099 Tumor location (lower ureter vs. non-lower ureter) 0.046 1.59 0.53 4.77 0.407 0.149 1.26 0.42 3.85 0.679 0.028 1.27 0.31 5.22 0.737 Intravesical chemotherapy (yes vs. no) 0.323 0.216 0.271 Adjuvant chemotherapy (yes vs. no) 0.172 < 0.001 1.51 0.67 3.40 0.318 0.228 LR test: log-rank test. aHR: adjusted hazard ratio a Variables with p < 0.15 from log-rank test were selected into multivariable Cox regression models b The variable was not included in the models because no event occurred in one category of the variable which restricted the estimation of adjusted hazard ratios. Regarding distant metastasis, 28 out of 169 patients (16.5%) experienced distant metastasis. The log rank test demonstrated that factors associated with distant metastasis were advanced T stage (≥ pT2) (p < 0.001), lympho-vascular invasion (p < 0.001), and receiving adjuvant chemotherapy (p < 0.001). (Table 2 ) Furthermore, multivariable Cox regression models showed that advanced T stage (≥ pT2), (aHR: 7.45,1.65–33.60, p = 0.007) and lympho-vascular invasion (aHR: 2.82, 1.26–6.27, p = 0.011) were independent risk factors of distant metastasis. (Fig. 2 ) Regarding all-cause death, 22 out of 169 patients (13%) died during the study period. Log-rank test explored associated factors of death were advanced T stage (≥ pT2) (p < 0.001), positive surgical margin (p = 0.013), lympho-vascular invasion (p = 0.002), and tumor location in the lower ureter (p = 0.028). (Table 2 ) Moreover, multivariable Cox regression models showed that advanced T stage (≥ pT2) (aHR: 4.71, 1.30–17.07, p = 0.018), lympho-vascular invasion (aHR: 2.93, 1.18–7.26, p = 0.021), and hemodialysis (aHR: 3.52, 1.1–11.24, p = 0.033) were independently associated with poor overall survival. (Fig. 3 ) Discussion In this retrospective cohort study of 169 UTUC patients without a history of or concurrent bladder cancer after RNUx, the five-year bladder recurrence-free survival (BRFS) was estimated at 66.6%. Our findings indicate that male gender, carcinoma in situ, and hypertension were associated with increased bladder recurrence. Additionally, advanced T stage and lymphovascular invasion were linked to reduced distant metastasis-free survival (DMFS) and overall survival (OS), while hemodialysis was associated with poorer OS. Although the mechanism causing bladder recurrence was not fully understanded, two primary theories have been proposed to explain the nature and pathogenesis. First, the monoclonal theory posits that coexisting tumors are derived from a single progenitor cell that has undergone malignant transformation. ( 15 ) During the surgery, coexsiting urothelial carcinoma from upper urianry tract implanted the bladder mucosa and trigger bladder recurrence. On the other hand, the field effect theory suggests that urothelial carcinomas arise secondary to numerous independent mutational events within urinary tract as a consequence of external cancer-causing influences. ( 16 ) Carcinogens in environment trigger several gene alterations of the bladder mucosa in the development of multifocal bladder urothelial carcinoma. These two theories are widely accepted as the primary explanations for synchronous or metachronous bladder recurrence. Under the monoclonal theory, tumor location, hydronephrosis, and pre-surgery URS with biopsy would be positively correlated to bladder recurrence. Meftun et al. revealed that pre-surgery URS is the independent predictor of bladder recurrence in patients with UTUC located in the kidney. (aHR:6.88, 2.41–19.65, p < 0.001).( 17 ) Similarly, Rajan et al. showed that pre-surgery URS impacts bladder recurrence but not adversely impact overall survival during a median follow-up of 9.2 years.( 11 ) A meta-analysis of 11 studies, including a total of 5053 patients, also concluded that pre-surgery URS was associated with an increased risk of bladder recurrence (aHR:1.47, 1.32–1.64, p < 0.01).( 12 ) The proposed mechanism is that manipulation and irrigation during ureteroscopy may facilitate tumor seeding and subsequent bladder recurrence.( 18 ) However, in our study, pre-surgery URS with biopsy was not significantly associated with BRFS, DMFS, or OS in our study. A similar finding was reported by a large retrospective study from Taiwan, which revealed that pre-surgery URS with or without biopsy was not associated with BRFS. ( 19 ) This discrepancy may be due to distinct genetic or environmental etiologies in Taiwan, where UTUC is often linked to aristolochic acid exposure from herbal medicines.( 20 ) Based on our results, pre-surgery URS appears to be safe before RNUx and does not increase the risk of bladder recurrence. Chen et al. reported hydronephrosis is a predictor for BRFS and disease-free survival.( 13 ) However, a subsequent meta-analysis of 22 studies showed hydronephrosis was not associated with BRFS (p = 0.12), though it was associated with poorer OS (aHR:1.26, 1.08–1.47, p = 0.004) and disease-free survival (aHR:1.25, 1.07–1.47, p = 0.005).( 21 ) It was hypothesized that hydronephrosis might cause outward expansion pressure pelvis or ureter wall, which promote tumor seeding to nearby tissues and increase outward pressure, resulting in reverse flow in lymphatics and vasculature, which facilitate tumor seeding.( 22 ) In contrast, our study did not provide evidence for the associations of hydronephrosis with BRFS, DMFS, or OS. Such a result is not in line with what we observed in the literature. Thus, further studies are required to clarify the findings. A retrospective cohort study in Taiwan reported that tumors located in the middle and lower ureter were associated with a higher risk of bladder recurrence compared to tumors in the upper ureter and renal pelvis.( 14 ) Other studies similarly showed ureter tumor had worse bladder recurrence free survival and disease-free survival.(( 23 – 25 ) Our result also aligns with these findings, showing that tumors in the lower ureter were associated with a higher risk of bladder recurrence (p = 0.046) and associated with worse overall survival (p = 0.028) compared to non-lower ureter tumors. The proximity of the lower ureter to the bladder, along with its narrower lumen, which may increase intraluminal pressure and urine flow has been hypothesized to promote tumor cell detachment and seeding. ( 26 ) Based on the field effect theory, the bladder urothelial mucosa exposed to cancerous environment such as prior or concurrent bladder cancer, adverse pathologic feature of UTUC (including high grade, carcinoma in situ, advanced T stage and lympho-vascular invasion) as well as the accumulation of biochemical carcinogens (such as hemodialysis and smoking) may undergo malignant transformation. Our study suggests that smoking and carcinoma in situ are independent factors of bladder recurrence after adjusting for confounding variables. (Fig. 1 ) This is consistent with previous reports which showed significant associations of tumor multifocality and smoking with bladder recurrence.( 25 ) Male gender is a significant increased risk factor for bladder recurrence in our study. Similarly, Lee et al. showed the same finding and suggested that male gender is a confounding factor for smoking due to a distinct difference observed in smoking status of genders.( 27 ) In our study, 24% (17/70) of male patients and 1% (1/90) of female patients had a history of smoking. Among the 17 male smokers, 47% (8/17) experienced bladder recurrence. This result is also consistent with findings of Lee et al. Our study has several limitations. First, it is a retrospective analysis of a single-center. Second, management of bladder cuff is mostly transurethral method which limiting the comparison with different surgical methods. Third, the relatively small sample size affects the statistical power of the analysis. Nonetheless, the study has several strengths, including the standardized surgical procedures and consistent follow-up conducted by 10 experienced surgeons, And the exclusion of patients with prior or concurrent bladder cancer, which minimizing confounding effects for bladder recurrence and providing valuable insights for clinical practice. Conclusion Bladder recurrence is a common event after RNUx in patients with non-metastatic UTUC. Our study identified male gender, smoking, and carcinoma in situ as significant risk factors for increased bladder recurrence. Pre-surgery URS was found to be safe and not associated with bladder recurrence. Additionally, advanced stage and lymphovascular invasion were identified as risk factors for distant metastasis, while advanced T stage and hemodialysis were associated with poorer overall survival. Given the relatively small sample size, further large-scale studies are warranted to validate these findings and guide future clinical management. Abbreviations UTUC Upper tract urothelial carcinoma RNUx Radical nephroureterectomy with bladder cuff excision BRFS Bladder recurrence-free survival DMFS Distant metastasis-free survival OS Overall survival URS Ureteroscopy Declarations There are no potential financial and non-financial conflicts of interest Ethics approval and consent to participate The present study, including its research protocols and data collection, were approved by the Institutional Review Board of Changhua Christian Hospital (CCH IRB No.231226). In view of the retrospective nature of the study, obtaining patients’ informed consent was waived. Consent for publication Not applicable. Clinical trial number Not applicable. Availability of data and materials Records and data pertaining to this study are stored in the secure medical records system of Changhua Christian Hospital. These data were used under license for the current study and are not publicly available. However, the data are available from the authors upon reasonable request. Competing interests The authors declare that they have no competing interests. Fundings None to declare. Authors' contributions YZC: project development and manuscript writing. TSK: data collection and data analysis. HJS: data collection and data analysis. JYW: data analysis, prepared figures, manuscript writing, and manuscript editing. All authors have read and approved the manuscript. Conflict of interests There are no conflicts of interest. Acknowledgements There is no potential financial and non-financial funding. References Lefort F, Rhanine Y, Larroquette M, Domblides C, Heraudet L, Sionneau B, et al. Clinical and Biological Differences between Upper Tract Carcinoma and Bladder Urothelial Cancer, Including Implications for Clinical Practice. Cancers (Basel). 2023;15(23). Raman JD, Messer J, Sielatycki JA, Hollenbeak CS. 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Predictors for Intravesical Recurrence Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A National Multicenter Analysis. Clin Genitourin Cancer. 2017;15(6):e1055-e61. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 30 Jun, 2025 Reviewers agreed at journal 22 Jun, 2025 Reviewers agreed at journal 20 Jun, 2025 Reviewers invited by journal 05 Jun, 2025 Editor invited by journal 16 Apr, 2025 Editor assigned by journal 15 Apr, 2025 Submission checks completed at journal 15 Apr, 2025 First submitted to journal 10 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6422108","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":468104867,"identity":"d22423e6-692b-429e-9369-12bc66c8a7a8","order_by":0,"name":"Yi-Chung Chen","email":"","orcid":"","institution":"Changhua Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yi-Chung","middleName":"","lastName":"Chen","suffix":""},{"id":468104868,"identity":"c08259b5-87d2-4c9c-baae-d9a04e7b7ebb","order_by":1,"name":"Ting-Shuo Kang","email":"","orcid":"","institution":"Changhua Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ting-Shuo","middleName":"","lastName":"Kang","suffix":""},{"id":468104869,"identity":"b8797188-4f69-4995-afee-1c76a0cf71d2","order_by":2,"name":"Hung-Jen Shih","email":"","orcid":"","institution":"Changhua Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hung-Jen","middleName":"","lastName":"Shih","suffix":""},{"id":468104870,"identity":"5c8d11b2-8d9f-4ffd-9d36-dad5a26fba11","order_by":3,"name":"Jiun-Yi Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYBACxoYDIMqGgYEZRLMRryUNoYWHSMsOQ2litDA3njH8XPDrvLx8O/MDhg9lhxnsJRIIOeyMsfTMvtuGGw6zGTDOOHeYgYewlrMbpHl7bjNuYGYwYOZtA2qRJqxl82/ennP285vZPzD/JVLLNmmeHwcSGw7zGDAzEqfl/Ddr3obk5A2HeQoO9pxL5+G5/wC/FsMZx5Jv8/yxs53ff3zjgx9l1nLsPQcIaQEqYGyDcEBqCcekPH8DkPxDUN0oGAWjYBSMZAAAh2RGd+ytiQIAAAAASUVORK5CYII=","orcid":"","institution":"Asia University","correspondingAuthor":true,"prefix":"","firstName":"Jiun-Yi","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-04-10 16:53:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6422108/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6422108/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84340483,"identity":"3b1e5bc3-2bd0-494a-8a49-acba2cf6f3a1","added_by":"auto","created_at":"2025-06-10 18:25:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36134,"visible":true,"origin":"","legend":"\u003cp\u003eCox-regression adjusted survival curves of BRFS by (a) sex or (b) CIS\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6422108/v1/46ed0f587882aba82b48b8dc.png"},{"id":84341834,"identity":"d7cea475-1f36-44e5-97f7-1546dd787d51","added_by":"auto","created_at":"2025-06-10 18:41:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":37612,"visible":true,"origin":"","legend":"\u003cp\u003eCox-regression adjusted survival curves of DMFS by (a) CIS or (b) lymphovascular invasion\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6422108/v1/63c218777bd1d96419895365.png"},{"id":84340484,"identity":"8dd2b6ae-1429-494e-9f48-ebea17b71477","added_by":"auto","created_at":"2025-06-10 18:25:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":31168,"visible":true,"origin":"","legend":"\u003cp\u003eCox-regression adjusted survival curves of OS by (a) pT2, (b) hemodialysis, or (c) lymphovascular invasion\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6422108/v1/439da0f9a67167f76c78a345.png"},{"id":84342155,"identity":"596f413b-3179-468b-82db-6342df2a7053","added_by":"auto","created_at":"2025-06-10 18:49:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":842936,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6422108/v1/bd341f07-946e-4d7a-902d-5741d572c7ce.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictive risk factors of bladder recurrence after radical nephroureterectomy for non-metastatic upper tract urothelial carcinoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eUrothelial carcinoma is the sixth most frequent type of cancer in United States. While bladder urothelial carcinoma accounts for 90\u0026ndash;95% of cases, upper urinary tract urothelial carcinoma (UTUC) is relatively rare, comprising only 5\u0026ndash;10% of all urothelial carcinomas.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Raman et al. reported a rise in the incidence of UTUC in the United States, increasing from 1.88 to 2.06 cases per 100,000 population.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) In contrast, Taiwan has reported an abnormally high incidence of UTUC, with a rate of 4 per 100,000, accounting for up to 30% of all urinary tract cancers.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eRadical nephroureterectomy with bladder cuff resection (RNUx) is the standard method for non-metastatic UTUC. Various surgical methods of bladder cuff resection have been employed, including extravesical, intravesical, and transurethral approaches. However, there is still no consensus regarding oncological outcomes in current guidelines. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) The oncologic outcome is associated with the stage and pathologic features of UTUC, and decisions regarding adjuvant chemotherapy after surgery generally depend on these factors. Additionally, the European Association of Urology (EAU) guidelines recommend a single post-operative intravesical chemotherapy following RNUx to reduce the risk of bladder recurrence. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDue to the ability of urothelial carcinoma cells to proliferate through urine and seed across the urinary system, the risk of bladder recurrence after surgery cannot be ignored. Bladder recurrence following RNUx has poorer oncological outcomes and increased medical costs. The incidence of bladder recurrence after surgery ranges from 33\u0026ndash;70% in the residual ureteral stump. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Moreover, predicting which patients will develop bladder recurrence remains challenging. Several risk factors have been linked to bladder recurrence, including multiple tumor foci, incomplete surgery, sex, age, lymphovascular invasion, tumor grade, and T stage. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Furthermore, ureteral tumors have been associated with worse oncologic outcomes compared to renal pelvis tumors. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDespite previous investigations, the risk factors of bladder recurrence are not yet fully understood and remain a subject of debate. Several studies have identified a history of concurrent or prior bladder cancer as a significant risk factor of bladder recurrence following RNUx. (\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) Unlike these studies, this present study aimed to identify predictive factors for bladder recurrence and oncologic outcomes in patients with non-metastatic UTUC undergoing RNUx, focusing exclusively on those without concurrent or prior bladder cancer to minimize effects of confounding factors.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e The present study was approved by the review board of our institution (CCH IRB No.231226). Patients who underwent RNUx from January 2010 to October 2023 in the Changhua Christian Hospital were retrospectively reviewed. All the operations were performed by ten experienced surgeons. Patients who had a pathological diagnosis of urothelial carcinoma of the renal pelvis or ureter and pathological staging of T1-3N0 were included. However, patients with bilateral UTUC, non-urothelial carcinoma of the ureter or the renal pelvis, other primary cancers, pathological staging of T4 or N1-3, concurrent bladder cancer, history of bladder cancer, previous endoscopic laser ablation of ureter or renal pelvis tumor history, or incomplete information were excluded. Patients were divided into two groups according to their bladder recurrence status after the operation.\u003c/p\u003e \u003cp\u003eData on patient medical records and clinical parameters were retrieved, including sex, age, pre-surgery ureteroscopy(URS), pre-surgery hydronephrosis, surgical method, tumor site, tumor location, clinical T stage, pathologic T stage, carcinoma in situ, surgical margin, lympho-vascular invasion, comorbidities (hypertension, diabetes mellitus, chronic kidney disease and hemodialysis status), smoking, adjuvant chemotherapy, intravesical chemotherapy, oncologic outcome (bladder recurrence and distant metastasis), mortality, and follow-up period. Hypertension, diabetes mellitus, chronic kidney disease, and hemodialysis were referred to ICD-9-CM codes used in the hospital. Tumor stage was evaluated according to the 2002 American Joint Committee Cancer TNM system. Tumor grade was reviewed by two pathologists and classified as low or high-grade using the 2004 World Health Organization grading system.\u003c/p\u003e \u003cp\u003e After the operation, patients were followed up according to National Comprehensive Cancer Network guidelines and outpatient clinic visits were arranged every 3 months every year. Bladder recurrence was defined based on the pathological report following transurethral biopsy of a bladder tumor during follow-up cystoscopy. If clinically indicated, computed tomography or magnetic resonance imaging were performed and distant metastasis was defined based on the radiological report such as lymph node metastasis or distant metastasis. Adjuvant chemotherapy and intravesical chemotherapy were administered to 26 and 10 patients, respectively, according to pathological stage and consent to treatment.\u003c/p\u003e \u003cp\u003eAll data analyses were conducted using IBM SPSS (version 22.0). Demographic and clinicopathologic characteristics were compared between the bladder recurrence and non-bladder recurrence groups using the chi-square test, or Fisher\u0026rsquo;s exact test when expected counts were small. The log-rank test and multivariable Cox regression analysis were performed to evaluate the associations between variables and bladder recurrence-free survival (BRFS), distant metastasis-free survival (DMFS), and overall survival (OS). Variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.15 from the log-rank test were included in the multivariable Cox regression models. Variables meeting this criterion but having no events in one of the categories were excluded from the Cox model due to unstable estimation of adjusted hazard ratios. A two-sided p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant for all hypothesis tests.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eInitially, 353 patients who underwent RNUx were reviewed. Among them, 184 patients were excluded due to bilateral UTUC (n\u0026thinsp;=\u0026thinsp;1), non-urothelial carcinoma of the ureter or the renal pelvis (n\u0026thinsp;=\u0026thinsp;27), other primary cancer (n\u0026thinsp;=\u0026thinsp;35), concurrent bladder cancer or bladder cancer history (n\u0026thinsp;=\u0026thinsp;52), pathological staging of T4 or N1-3 (n\u0026thinsp;=\u0026thinsp;21), previous endoscopic laser ablation of ureter or renal pelvis tumor history (n\u0026thinsp;=\u0026thinsp;3), and incomplete information (n\u0026thinsp;=\u0026thinsp;45). As a result, 169 patients were eligible for analysis with an average followed-up period of 41.7\u0026thinsp;\u0026plusmn;\u0026thinsp;34.5 months (ranging from 0.4 to 138.2 months, IQR:51.8 months). The bladder cuff was managed via a transurethral approach in 151 cases (89.3%) or an extravesical approach in 18 cases (10.7%). During the follow-up period, 44 patients (26%) had bladder recurrence who were then categorized into the bladder recurrence group, while the remaining 125 patients (74%) were categorized into the non-bladder recurrence group. Patients\u0026rsquo; demographics and clinicopathologic characteristics were shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics and clinicopathologic characteristics of 169 patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;169)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eBladder recurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo (n\u0026thinsp;=\u0026thinsp;125)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes (n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;70 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;70 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePre-surgery URS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.989\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSurgical method\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOpen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLaparoscope\u003c/p\u003e \u003cp\u003e/Robotic-assisted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTumor site\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.702\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRenal Pelvis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.557 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMiddle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMore than one site\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTumor grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1.000 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ecT stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.650\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003epT stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epTis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.306 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epTa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCarcinoma in situ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.387 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSurgical margin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.166 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e124\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLympho-vascular invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.799\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHydronephrosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.903\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.217\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.698\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eChronic kidney disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.915\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHemodialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1.000 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.085 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIntravesical chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.457 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e159\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAdjuvant chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.199\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e143\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003e Fisher\u0026rsquo;s exact test due to small expected counts\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn general, the BRFS rate was 81.8% at 12 months after RNUx, 69.6% at 36 months after RNUx, and 66.6% at 60 months after RNUx. Results from log-rank tests revealed some associated factors of bladder recurrence, including male (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), smoking (p\u0026thinsp;=\u0026thinsp;0.023), and tumor location in the lower ureter (p\u0026thinsp;=\u0026thinsp;0.046). Multivariate Cox regression models showed that male (adjusted Hazard Ration [aHR]: 0.41 for females vs. males, 95% Confidence Interval: 0.21\u0026ndash;0.78, p\u0026thinsp;=\u0026thinsp;0.007), carcinoma in situ (aHR: 2.62, 1.07\u0026ndash;6.41, p\u0026thinsp;=\u0026thinsp;0.035) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and hypertension (aHR: 2.25, 1.13\u0026ndash;4.49, p\u0026thinsp;=\u0026thinsp;0.022) were related to worse bladder recurrence rate. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\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\u003eCox regression analyses predicting bladder recurrence free survival, distant metastasis free survival and overall survival\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"18\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c18\" colnum=\"18\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eBladder recurrence free survival\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eDistant metastasis free survival\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c17\" namest=\"c12\"\u003e \u003cp\u003eOverall survival\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c18\" namest=\"c18\"\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eCox regression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c11\" namest=\"c8\"\u003e \u003cp\u003eCox regression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c16\" namest=\"c12\"\u003e \u003cp\u003eCox regression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep-value of LR test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eaHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLower limit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUpper limit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep-value of LR test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eaHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLower limit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eUpper limit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003ep-value of LR test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eaHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eLower limit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eUpper limit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male vs. female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.781\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (\u0026ge;\u0026thinsp;70 vs. \u0026lt;70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.405\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.654\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-surgery URS (yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.924\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.746\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.480\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOP method (open vs. laparoscope/robotic-assisted)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.263\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.434\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.672\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor site (left vs. right)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.986\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.078\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.487\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor grade (high vs. low)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.815\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.081\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e0.117\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT stage (\u0026ge;\u0026thinsp;pT2 vs.\u0026lt;pT2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.624\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e33.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e4.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e17.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e \u003cp\u003e\u003cb\u003e0.018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCarcinoma in situ (yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.132\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.035\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.779\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.751\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical margin (yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.071\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.484\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e0.013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e17.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e \u003cp\u003e0.318\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLympho-vascular invasion \u003c/p\u003e \u003cp\u003e(yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.405\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e6.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e0.011\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e7.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHydronephrosis (yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.710\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.484\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.709\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension (yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.067\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.644\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.358\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus (yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.680\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.988\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.897\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic kidney disease\u003c/p\u003e \u003cp\u003e(yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.894\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e0.051\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e9.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e \u003cp\u003e0.172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemodialysis (yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.820\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.334\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e0.076\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e3.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e11.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e \u003cp\u003e\u003cb\u003e0.033\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking (yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.598\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e0.099\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location (lower ureter vs. non-lower ureter)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.046\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.149\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.679\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e5.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e \u003cp\u003e0.737\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntravesical chemotherapy \u003c/p\u003e \u003cp\u003e(yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.216\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant chemotherapy\u003c/p\u003e \u003cp\u003e(yes vs. no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.318\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.228\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c18\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"18\"\u003eLR test: log-rank test. aHR: adjusted hazard ratio\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"18\"\u003e\u003csup\u003ea\u003c/sup\u003e Variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.15 from log-rank test were selected into multivariable Cox regression models\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"18\"\u003e\u003csup\u003eb\u003c/sup\u003e The variable was not included in the models because no event occurred in one category of the variable which restricted the estimation of adjusted hazard ratios.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRegarding distant metastasis, 28 out of 169 patients (16.5%) experienced distant metastasis. The log rank test demonstrated that factors associated with distant metastasis were advanced T stage (\u0026ge;\u0026thinsp;pT2) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), lympho-vascular invasion (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and receiving adjuvant chemotherapy (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) Furthermore, multivariable Cox regression models showed that advanced T stage (\u0026ge;\u0026thinsp;pT2), (aHR: 7.45,1.65\u0026ndash;33.60, p\u0026thinsp;=\u0026thinsp;0.007) and lympho-vascular invasion (aHR: 2.82, 1.26\u0026ndash;6.27, p\u0026thinsp;=\u0026thinsp;0.011) were independent risk factors of distant metastasis. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRegarding all-cause death, 22 out of 169 patients (13%) died during the study period. Log-rank test explored associated factors of death were advanced T stage (\u0026ge;\u0026thinsp;pT2) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), positive surgical margin (p\u0026thinsp;=\u0026thinsp;0.013), lympho-vascular invasion (p\u0026thinsp;=\u0026thinsp;0.002), and tumor location in the lower ureter (p\u0026thinsp;=\u0026thinsp;0.028). (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) Moreover, multivariable Cox regression models showed that advanced T stage (\u0026ge;\u0026thinsp;pT2) (aHR: 4.71, 1.30\u0026ndash;17.07, p\u0026thinsp;=\u0026thinsp;0.018), lympho-vascular invasion (aHR: 2.93, 1.18\u0026ndash;7.26, p\u0026thinsp;=\u0026thinsp;0.021), and hemodialysis (aHR: 3.52, 1.1\u0026ndash;11.24, p\u0026thinsp;=\u0026thinsp;0.033) were independently associated with poor overall survival. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective cohort study of 169 UTUC patients without a history of or concurrent bladder cancer after RNUx, the five-year bladder recurrence-free survival (BRFS) was estimated at 66.6%. Our findings indicate that male gender, carcinoma in situ, and hypertension were associated with increased bladder recurrence. Additionally, advanced T stage and lymphovascular invasion were linked to reduced distant metastasis-free survival (DMFS) and overall survival (OS), while hemodialysis was associated with poorer OS.\u003c/p\u003e \u003cp\u003eAlthough the mechanism causing bladder recurrence was not fully understanded, two primary theories have been proposed to explain the nature and pathogenesis. First, the monoclonal theory posits that coexisting tumors are derived from a single progenitor cell that has undergone malignant transformation. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) During the surgery, coexsiting urothelial carcinoma from upper urianry tract implanted the bladder mucosa and trigger bladder recurrence. On the other hand, the field effect theory suggests that urothelial carcinomas arise secondary to numerous independent mutational events within urinary tract as a consequence of external cancer-causing influences. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Carcinogens in environment trigger several gene alterations of the bladder mucosa in the development of multifocal bladder urothelial carcinoma. These two theories are widely accepted as the primary explanations for synchronous or metachronous bladder recurrence.\u003c/p\u003e \u003cp\u003eUnder the monoclonal theory, tumor location, hydronephrosis, and pre-surgery URS with biopsy would be positively correlated to bladder recurrence. Meftun et al. revealed that pre-surgery URS is the independent predictor of bladder recurrence in patients with UTUC located in the kidney. (aHR:6.88, 2.41\u0026ndash;19.65, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) Similarly, Rajan et al. showed that pre-surgery URS impacts bladder recurrence but not adversely impact overall survival during a median follow-up of 9.2 years.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) A meta-analysis of 11 studies, including a total of 5053 patients, also concluded that pre-surgery URS was associated with an increased risk of bladder recurrence (aHR:1.47, 1.32\u0026ndash;1.64, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01).(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) The proposed mechanism is that manipulation and irrigation during ureteroscopy may facilitate tumor seeding and subsequent bladder recurrence.(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) However, in our study, pre-surgery URS with biopsy was not significantly associated with BRFS, DMFS, or OS in our study. A similar finding was reported by a large retrospective study from Taiwan, which revealed that pre-surgery URS with or without biopsy was not associated with BRFS. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) This discrepancy may be due to distinct genetic or environmental etiologies in Taiwan, where UTUC is often linked to aristolochic acid exposure from herbal medicines.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) Based on our results, pre-surgery URS appears to be safe before RNUx and does not increase the risk of bladder recurrence.\u003c/p\u003e \u003cp\u003eChen et al. reported hydronephrosis is a predictor for BRFS and disease-free survival.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) However, a subsequent meta-analysis of 22 studies showed hydronephrosis was not associated with BRFS (p\u0026thinsp;=\u0026thinsp;0.12), though it was associated with poorer OS (aHR:1.26, 1.08\u0026ndash;1.47, p\u0026thinsp;=\u0026thinsp;0.004) and disease-free survival (aHR:1.25, 1.07\u0026ndash;1.47, p\u0026thinsp;=\u0026thinsp;0.005).(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) It was hypothesized that hydronephrosis might cause outward expansion pressure pelvis or ureter wall, which promote tumor seeding to nearby tissues and increase outward pressure, resulting in reverse flow in lymphatics and vasculature, which facilitate tumor seeding.(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) In contrast, our study did not provide evidence for the associations of hydronephrosis with BRFS, DMFS, or OS. Such a result is not in line with what we observed in the literature. Thus, further studies are required to clarify the findings.\u003c/p\u003e \u003cp\u003eA retrospective cohort study in Taiwan reported that tumors located in the middle and lower ureter were associated with a higher risk of bladder recurrence compared to tumors in the upper ureter and renal pelvis.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) Other studies similarly showed ureter tumor had worse bladder recurrence free survival and disease-free survival.((\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) Our result also aligns with these findings, showing that tumors in the lower ureter were associated with a higher risk of bladder recurrence (p\u0026thinsp;=\u0026thinsp;0.046) and associated with worse overall survival (p\u0026thinsp;=\u0026thinsp;0.028) compared to non-lower ureter tumors. The proximity of the lower ureter to the bladder, along with its narrower lumen, which may increase intraluminal pressure and urine flow has been hypothesized to promote tumor cell detachment and seeding. (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eBased on the field effect theory, the bladder urothelial mucosa exposed to cancerous environment such as prior or concurrent bladder cancer, adverse pathologic feature of UTUC (including high grade, carcinoma in situ, advanced T stage and lympho-vascular invasion) as well as the accumulation of biochemical carcinogens (such as hemodialysis and smoking) may undergo malignant transformation. Our study suggests that smoking and carcinoma in situ are independent factors of bladder recurrence after adjusting for confounding variables. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) This is consistent with previous reports which showed significant associations of tumor multifocality and smoking with bladder recurrence.(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eMale gender is a significant increased risk factor for bladder recurrence in our study. Similarly, Lee et al. showed the same finding and suggested that male gender is a confounding factor for smoking due to a distinct difference observed in smoking status of genders.(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) In our study, 24% (17/70) of male patients and 1% (1/90) of female patients had a history of smoking. Among the 17 male smokers, 47% (8/17) experienced bladder recurrence. This result is also consistent with findings of Lee et al.\u003c/p\u003e \u003cp\u003eOur study has several limitations. First, it is a retrospective analysis of a single-center. Second, management of bladder cuff is mostly transurethral method which limiting the comparison with different surgical methods. Third, the relatively small sample size affects the statistical power of the analysis. Nonetheless, the study has several strengths, including the standardized surgical procedures and consistent follow-up conducted by 10 experienced surgeons, And the exclusion of patients with prior or concurrent bladder cancer, which minimizing confounding effects for bladder recurrence and providing valuable insights for clinical practice.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBladder recurrence is a common event after RNUx in patients with non-metastatic UTUC. Our study identified male gender, smoking, and carcinoma in situ as significant risk factors for increased bladder recurrence. Pre-surgery URS was found to be safe and not associated with bladder recurrence. Additionally, advanced stage and lymphovascular invasion were identified as risk factors for distant metastasis, while advanced T stage and hemodialysis were associated with poorer overall survival. Given the relatively small sample size, further large-scale studies are warranted to validate these findings and guide future clinical management.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUTUC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUpper tract urothelial carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRNUx\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRadical nephroureterectomy with bladder cuff excision\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBRFS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBladder recurrence-free survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDMFS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDistant metastasis-free survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOverall survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eURS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUreteroscopy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eThere are no potential financial and non-financial conflicts of interest\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe present study, including its research protocols and data collection, were approved by the Institutional Review Board of Changhua Christian\u0026nbsp;Hospital\u0026nbsp;(CCH IRB No.231226). In view of the retrospective nature of the study, obtaining patients\u0026rsquo; informed consent was waived.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eClinical trial number\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eRecords and data pertaining to this study are stored in the secure medical records system of Changhua Christian Hospital. These data were used under license for the current study and are not publicly available. However, the data are available from the authors upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFundings\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNone to declare.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026apos; contributions\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eYZC: project development and manuscript writing. TSK: data collection and data analysis. HJS: data collection and data analysis. JYW: data analysis,\u0026nbsp;prepared figures, manuscript writing, and manuscript editing. All authors have read and approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConflict of interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThere are no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThere is no potential financial and non-financial funding.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLefort F, Rhanine Y, Larroquette M, Domblides C, Heraudet L, Sionneau B, et al. Clinical and Biological Differences between Upper Tract Carcinoma and Bladder Urothelial Cancer, Including Implications for Clinical Practice. Cancers (Basel). 2023;15(23).\u003c/li\u003e\n\u003cli\u003eRaman JD, Messer J, Sielatycki JA, Hollenbeak CS. Incidence and survival of patients with carcinoma of the ureter and renal pelvis in the USA, 1973-2005. BJU Int. 2011;107(7):1059-64.\u003c/li\u003e\n\u003cli\u003eChen JS, Lu CL, Huang LC, Shen CH, Chen SC. Chronic Kidney Disease is Associated With Upper Tract Urothelial Carcinoma: A Nationwide Population-Based Cohort Study in Taiwan. Medicine (Baltimore). 2016;95(14):e3255.\u003c/li\u003e\n\u003cli\u003eXylinas E, Rink M, Cha EK, Clozel T, Lee RK, Fajkovic H, et al. Impact of distal ureter management on oncologic outcomes following radical nephroureterectomy for upper tract urothelial carcinoma. Eur Urol. 2014;65(1):210-7.\u003c/li\u003e\n\u003cli\u003eLi CC, Chang TH, Wu WJ, Ke HL, Huang SP, Tsai PC, et al. Significant predictive factors for prognosis of primary upper urinary tract cancer after radical nephroureterectomy in Taiwanese patients. Eur Urol. 2008;54(5):1127-34.\u003c/li\u003e\n\u003cli\u003eRoupret M, Seisen T, Birtle AJ, Capoun O, Comperat EM, Dominguez-Escrig JL, et al. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2023 Update. Eur Urol. 2023;84(1):49-64.\u003c/li\u003e\n\u003cli\u003eStrong DW, Pearse HD. Recurrent urothelial tumors following surgery for transitional cell carcinoma of the upper urinary tract. Cancer. 1976;38(5):2173-83.\u003c/li\u003e\n\u003cli\u003eJang NY, Kim IA, Byun SS, Lee SE, Kim JS. Patterns of failure and prognostic factors for locoregional recurrence after radical surgery in upper urinary tract transitional cell carcinoma: implications for adjuvant radiotherapy. Urol Int. 2013;90(2):202-6.\u003c/li\u003e\n\u003cli\u003eYoo S, You D, Jeong IG, Hong B, Hong JH, Ahn H, et al. Impact of Tumor Location on Local Recurrence After Nephroureterectomy for Upper Tract Urothelial Carcinoma: Implications for Adjuvant Radiotherapy. Clin Genitourin Cancer. 2017;15(2):e199-e204.\u003c/li\u003e\n\u003cli\u003eSoria F, Shariat SF, Lerner SP, Fritsche HM, Rink M, Kassouf W, et al. Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC). World J Urol. 2017;35(3):379-87.\u003c/li\u003e\n\u003cli\u003eVeeratterapillay R, Geraghty R, Pandian R, Roy C, Stenhouse G, Bird C, et al. Ten-year survival outcomes after radical nephroureterectomy with a risk-stratified approach using prior diagnostic ureteroscopy: a single-institution observational retrospective cohort study. BJU Int. 2022;129(6):744-51.\u003c/li\u003e\n\u003cli\u003eSharma V, Miest TS, Juvet TS, Toussi A, Packiam V, Chamie K, et al. The Impact of Upper Tract Urothelial Carcinoma Diagnostic Modality on Intravesical Recurrence after Radical Nephroureterectomy: A Single Institution Series and Updated Meta-Analysis. J Urol. 2021;206(3):558-67.\u003c/li\u003e\n\u003cli\u003eChen IA, Chang CH, Huang CP, Wu WJ, Li CC, Chen CH, et al. Factors Predicting Oncological Outcomes of Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma in Taiwan. Front Oncol. 2021;11:766576.\u003c/li\u003e\n\u003cli\u003eHuang YC, Wang HJ, Sung MT, Chuang YC, Chen YT, Cheng YT, et al. The lowest level of tumor involvement is a significant prognostic factor for upper tract urothelial carcinoma after radical nephroureterectomy: A large retrospective cohort study. Front Oncol. 2022;12:1031774.\u003c/li\u003e\n\u003cli\u003eHabuchi T, Takahashi R, Yamada H, Kakehi Y, Sugiyama T, Yoshida O. Metachronous multifocal development of urothelial cancers by intraluminal seeding. Lancet. 1993;342(8879):1087-8.\u003c/li\u003e\n\u003cli\u003eJones TD, Wang M, Eble JN, MacLennan GT, Lopez-Beltran A, Zhang S, et al. Molecular evidence supporting field effect in urothelial carcinogenesis. Clin Cancer Res. 2005;11(18):6512-9.\u003c/li\u003e\n\u003cli\u003eCulpan M, Cakici MC, Keser F, Yalcin MY, Kargi T, Kayar R, et al. Biopsy with Ureterorenoscopy Before Radical Nephroureterectomy is Associated with Increased Intravesical Recurrence in Urothelial Cancer Located in the Kidney. Turk J Urol. 2022;48(6):431-9.\u003c/li\u003e\n\u003cli\u003eIzol V, Deger M, Ozden E, Bolat D, Argun B, Baltaci S, et al. The Effect of Diagnostic Ureterorenoscopy on Intravesical Recurrence in Patients Undergoing Nephroureterectomy for Primary Upper Tract Urinary Carcinoma. Urol Int. 2021;105(3-4):291-7.\u003c/li\u003e\n\u003cli\u003eChen CY, Chang CH, Yang CR, Hsieh KL, Tsing WH, Chen IA, et al. Prognostic factors of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. World J Urol. 2024;42(1):22.\u003c/li\u003e\n\u003cli\u003eDickman KG, Chen CH, Grollman AP, Pu YS. Aristolochic acid-containing Chinese herbal medicine and upper urinary tract urothelial carcinoma in Taiwan: a narrative review. World J Urol. 2023;41(4):899-907.\u003c/li\u003e\n\u003cli\u003eYe T, Yang X, Lv P, Liu H, Ye Z. Prognostic Value of Preoperative Hydronephrosis in Patients Undergoing Radical Nephroureterectomy for Upper Tract Urinary Carcinoma: A Systematic Review and Meta-Analysis. Front Oncol. 2020;10:600511.\u003c/li\u003e\n\u003cli\u003eChung PH, Krabbe LM, Darwish OM, Westerman ME, Bagrodia A, Gayed BA, et al. Degree of hydronephrosis predicts adverse pathological features and worse oncologic outcomes in patients with high-grade urothelial carcinoma of the upper urinary tract. Urol Oncol. 2014;32(7):981-8.\u003c/li\u003e\n\u003cli\u003eYu LC, Chang CH, Huang CP, Huang CY, Hong JH, Tai TY, et al. Prognostic Significance of Primary Tumor Location in Upper Tract Urothelial Carcinoma Treated with Nephroureterectomy: A Retrospective, Multi-Center Cohort Study in Taiwan. J Clin Med. 2020;9(12).\u003c/li\u003e\n\u003cli\u003eChen TS, Chen YT, Wang HJ, Chiang PH, Yang WC, Lee WC, et al. The Prognostic Impact of Tumor Location in pT3N0M0 Upper Urinary Tract Urothelial Carcinoma: A Retrospective Cohort Study. Front Oncol. 2022;12:850874.\u003c/li\u003e\n\u003cli\u003eLi YR, Yu KJ, Chang YH, Lin PH, Shao IH, Kan HC, et al. Predictors of Intravesical Recurrence After Radical Nephroureterectomy and Prognosis in Patients with Upper Tract Urothelial Carcinoma. Cancer Manag Res. 2020;12:7439-50.\u003c/li\u003e\n\u003cli\u003eZigeuner RE, Hutterer G, Chromecki T, Rehak P, Langner C. Bladder tumour development after urothelial carcinoma of the upper urinary tract is related to primary tumour location. BJU Int. 2006;98(6):1181-6.\u003c/li\u003e\n\u003cli\u003eLee CH, Ku JY, Jeong CW, Ku JH, Kwak C, Kim HH, et al. Predictors for Intravesical Recurrence Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A National Multicenter Analysis. Clin Genitourin Cancer. 2017;15(6):e1055-e61.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"buro","sideBox":"Learn more about [BMC Urology](http://bmcurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/buro/default.aspx","title":"BMC Urology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"upper tract urothelial carcinoma, bladder recurrence, radical nephroureterectomy","lastPublishedDoi":"10.21203/rs.3.rs-6422108/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6422108/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe aim of our study was to explore predictive factors for bladder recurrence and oncologic outcomes in patients with non-metastatic upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy with bladder cuff excision (RNUx).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe retrospective cohort study enrolled 169 patients after RNUx in Changhua Christian Hospital between January 2010 and October 2023. Patients were divided into two groups of either experience bladder recurrence (n\u0026thinsp;=\u0026thinsp;44) or not (n\u0026thinsp;=\u0026thinsp;125). Data on clinical parameters, pre-surgery ureteroscopy, pre-surgery hydronephrosis, pathologic features, comorbidities, smoking, adjuvant chemotherapy, and intravesical chemotherapy were collected from patients\u0026rsquo; medical records. The log-rank test and multivariable Cox regression analysis were performed to identify variables associated with bladder recurrence-free survival (BRFS), distant metastasis-free survival (DMFS), and overall survival (OS).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOur finding shows that the BRFS rate was 81.8% at 12 months and 69.6% at 36 months after RNUx. Cox regression models revealed that male (aHR: 0.41 for females, 95% CI: 0.21\u0026ndash;0.78, p\u0026thinsp;=\u0026thinsp;0.007), carcinoma in situ (aHR: 2.62, 95% CI: 1.07\u0026ndash;6.41, p\u0026thinsp;=\u0026thinsp;0.035) and hypertension (aHR:2.25, 95% CI: 1.13\u0026ndash;4.49, p\u0026thinsp;=\u0026thinsp;0.022) were risk factors of bladder recurrence. Furthermore, advanced stage and lymphovascular invasion were identified as risk factors of DMFS, and advanced T stage and hemodialysis were associated with poorer OS.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur study identified several significant risk factors of bladder recurrence, distant metastasis, and all-cause death. These findings provide a reference of clinical care. A more frequent surveillance schedule may be helpful for these patients.\u003c/p\u003e","manuscriptTitle":"Predictive risk factors of bladder recurrence after radical nephroureterectomy for non-metastatic upper tract urothelial carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-10 18:25:43","doi":"10.21203/rs.3.rs-6422108/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-06-30T07:12:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"31978559738447842740079252807053860205","date":"2025-06-22T23:45:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"298715512264822629109026417622774760371","date":"2025-06-20T23:41:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-05T18:43:29+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-16T09:01:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-15T10:46:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-15T10:44:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Urology","date":"2025-04-10T16:47:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"buro","sideBox":"Learn more about [BMC Urology](http://bmcurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/buro/default.aspx","title":"BMC Urology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a7706dca-6f12-4255-8661-83a4234ea2c8","owner":[],"postedDate":"June 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-06-10T18:25:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-10 18:25:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6422108","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6422108","identity":"rs-6422108","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}