Development and validation of a predictive model for  intravesical recurrence after radical nephroureterectomy： a multi-center study

Development and validation of a predictive model for intravesical recurrence after radical nephroureterectomy： a multi-center study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Development and validation of a predictive model for intravesical recurrence after radical nephroureterectomy： a multi-center study cheng wang, biao zhang, ziming kang, shuzhen ou, pingheng li, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5094557/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The high incidence of incurrence recurrence(IVR) after radical nephroureterectomy (RNU) is a characteristic of upper urinary tract urothelial carcinoma (UTUC), which has a significant impact on the survival outcome of patients. This study aimed to construct nomogram using data from multicenter data to predict IVR in patients with UTUC. Methods Clinical data of 515 UTUC patients after RNU were gathered from three medical centers between 2012 and 2022. The factors associated with IVR were analyzed by univariate and multivariate Cox proportional risk models in one center as training cohort, and included independent risk factors into nomogram models predicting IVR-free survival (IVRFS). Another two centers were collected as the external cohort to validate the predictive accuracy and discriminative ability of the nomogram. Results Ureteroscopy, hydronephrosis, the history of bladder cancer, surgical margin and tumor grade were associated with IVR after UTUC (P < 0.05). The C-index of the nomogram in the training cohort were 0.722. The C-index of the nomograms in the external validation cohort were 0.767.Receiver operating characteristic (ROC) curves, calibration curves, and survival curves all demonstrated good predictive performance of the nomogram. Conclusion Ureteroscopy, hydronephrosis, the history of bladder cancer, surgical margin and tumor grade can be used to independently predict IVR after RNU. The nomogram was built based on these factors had good differentiation and conformity, which can assist clinicians in assessing individualized IVR rates and making optimal treatment decisions. Health sciences/Oncology Health sciences/Risk factors upper tract urothelial carcinoma intravesical recurrence risk factor nomogram Predictive model Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Urothelial carcinomas are the 6th most frequently diagnosed tumor in the developed countries and may be located in the lower genitourinary tract (urethra and bladder) or upper genitourinary tract (ureter and pyelocaliceal system) [ 1 ] . Upper tract urothelial carcinoma (UTUC) is a relatively rare entity, accounting for 5–10% of all urothelial tumors. The estimated annual incidence is 2 cases per 100,000 in western countries [ 2 ] .Radical nephroureterectomy (RNU) with bladder sleeve resection is the standard surgical treatment for UTUC, especially for high-risk patients. UTUC is more invasive and has a poor prognosis even after RNU and sleeve cystectomy in time, as 22% ~ 47% of patients still have an intravesical recurrence (IVR) during the follow-up period [ 3 ] . IVR mostly occurred within the first year postoperatively [ 4 ] . Once IVR occurs, patients have to undergo additional adjuvant treatment, such as transurethral bladder tumor resection surgery and intravesical instillation chemotherapy [ 5 ] . Yamashita et al. also indicated that IVR may reduce the 5-year survival rate of patient [ 6 ] . Therefore, how to identify the risk factors of IVR after RNU early has become a hot research topic in recent years. Now, some studies have reported that positive preoperative urine cytology, preoperative diagnostic ureteroscopic, tumor stage, grade, surgical method, lymphovascular invasion and other factors are independent risk factors for IVR after RNU [ 7 – 9 ] . However factors that reliably predict IVR have not been identified. Thus, how to leverage patient stratification tools to better identify patients who may have IVR at an early stage has become a timely issue to be addressed [ 10 ] . Xylinas et al. constructed prediction models based on a larger population from Western countries [ 11 ] ; however, For the Chinese population, there are significant differences in race, dietary habits, lifestyle choices, and exposure to common carcinogenic factors, especially aristolochic acid, compared with patients in Western countries [ 12 , 13 ] . The purpose of this study was to investigate risk factors for IVR in patients with UTUC, and we developed a nomogram and hope to assist the urologist to optimize clinical decision-making. Materials and methods Data acquisition This retrospective study was approved by the Medical Ethics Committee of the the first/Second Hospital of Lanzhou University and Gansu Provincial Hospital. Informed consent was obtained from all eligible participants in advance. The data involved in this retrospective study were collected prospectively from primary UTUC patients who underwent RNU in these center from 2012 to 2022.Inclusion criteria were: (1) patients with pathological diagnosis of UTUC; (2) patients with primary disease; (3) patients with unilateral disease; (4) patients with RNU combined with cystic sleeve resection;(5) patients with complete follow-up data. Exclusion criteria were: (1) patients with bilateral UTUC; (2) patients with no RNU combined with cystectomy; (3) patients with metastatic uroepithelial carcinoma. Clinicopathological data We collected the following clinicopathological features of patients for analysis: gender, age at the first diagnosis, body mass index (BMI), tumor laterality, pathologic tumor stage (pT), lymph node status, tumor grade, tumor size, tumor location, surgery margin positivity. Patients with previous history of hypertension, diabetes, and bladder cancer, preoperative urine cytology, presence of hydronephrosis on the affected side, diagnostic ureteroscopy. All resected tumor specimens were sent for pathological examination by senior pathologists. The pathologic tumor stage and grade were evaluated according to the 2009 International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) TNM classification system (Edge and Compton 2010) and the 2016 World Health Organization (WHO) grading system (Humphrey et al. 2016). In addition to the preoperative detailed baseline information, we also collected the intraoperative and postoperative outcomes of radical nephroureterectomy. The outcome during the operation includes the operation time, the amount of bleeding during the operation and whether there is damage to the surrounding organs. The postoperative outcome includes the recovery time of gastrointestinal function, the length of hospital stay, the occurrence of complications such as infection, urinary fistula, and the retention time of the drainage tube. Follow-up We monitored patients every 3 months during the first 2 years after surgery and every 6 months thereafter until 5 years. Follow-up assessments encompassed blood analyses, cystoscopy, ultrasound imaging of the urinary system, CT scans of the chest and abdomen, urine cytology, and urography procedures. When necessary, a bone scan, PET/CT or MRI examination was selectively carried out. Intravesical recurrence-free survival (IVRFS) was defined as the time from the date of RNU to the date of the first recurrence on imaging examination. Statistical analysis Patients of The Second Hospital of Lanzhou University Hospital were enrolled in the training cohort and validated in the cohort of The First Hospital of Lanzhou University Hospital and Gansu Provincial Hospital. Prognostic risk factors related to IVR were assessed by univariate and multivariate Cox regression analyses models in the training cohort, the multivariate Cox regression results were then integrated into the nomogram. The 1-/3-/5-/8-year IVRFS probabilities were estimated using the nomogram. Receiver operating characteristic (ROC) analyses were conducted in both cohorts, and the area under the ROC curve (AUC) and concordance index (C-index) were used to evaluate discrimination ability. To validate the accuracy of the model, calibration curves were drawn from 1000 bootstrap samples from the training and validation cohorts. All p-values were obtained from two-sided tests, and p < 0.05 indicated that the difference was statistically significant. R software (Version 4.3.2) and IBM SPSS Statistics (Version 26) were utilized to complete all statistical analyses and figures. Results Characteristics of patients and disease A cohort of 515 patients who met the specified inclusion and exclusion criteria were included in the study, with 363 patients in the training cohort and 152 patients in the validation cohort. The demographic and clinicopathological variables are summarized in Table 1.There were no significant diferences between the two cohorts except for age, ureteroscope, The location of tumour, grade. In the training cohort ,76 patients (20.9%) developed IVR after RNU, of which 48 patients (63.2%) developed IVR within 1 year after RNU, 22 patients (28.9%) developed IVR in 1-3 years (>1 year and ≤3 years) after RNU, and others had IVR more than 3 years. In the validation cohort , 32 patients (21.1%) developed IVR after RNU, of which 23 patients (71.9%) developed IVR within 1 year after RNU, 6 patients (18.8%) developed IVR in 1-3 years (>1 year and ≤3 years) after RNU, and others had IVR more than 3 years(Table 2). Table 1 Basic clinical characteristics of patients with UTUC variables Training cohort n=363（%） validation cohort n=152（%） P value Gender Male Female Age ＜65y ≥65y BMI（kg/m²） ＜18.5 ≥18.5and＜24 ≤24 Hypertension Yes No Diabetes Yes No Hydronephrosis Yes No Hematuresis yes no The history of Bladder cancer Yes no Ureteroscope yes no Surgical method open laparoscope Robot-assisted The location of tumour pelvis ureter both T-stage Tis/Ta/T1 T2/T3/T4 Lymph node status pN0/pNx pN+ Grade Low High Margin Yes No IVR 206（56.7） 157（43.3） 150（41.3） 213（58.7） 18（5） 177（48.7） 168（46.3） 106（29.2） 257（70.8） 36（9.9） 327（90.1） 214（59.0） 149（41.0） 264（72.7） 99（27.3） 62（17.1） 301（82.9） 81（22.3） 282（77.7） 18（5） 325（89.5） 20（5.5） 188（51.8） 150（41.3） 25（6.9） 94（25.9） 269（74.1） 314（86.5） 49（13.5） 83（22.9） 280（77.1） 32（8.8） 331（91.2） 76（20.9） 80（52.6） 72（47.4） 48（31.6） 104（68.4） 13（8.6） 81（53.2） 58（38.2） 51（33.6） 101（66.4） 10（6.6） 142（93.4） 81（53.3） 71（46.7） 112（73.7） 40（26.3） 31（20.4） 121（79.6） 56（36.8） 96（63.2） 13（8.6） 135（88.8） 4（2.6） 57（37.5） 82（53.9） 13（8.6） 44（28.9） 108（71.1） 140（92.1） 12（7.9） 57（37.5） 95（62.5） 6（3.9） 146（96.1） 32（21.1） 0.391 0.038 0.114 0.328 0.226 0.236 0.823 0.372 0.001 0.122 0.012 0.476 0.073 0.001 0.054 0.774 Table 2 The time characteristics of IVR after RNU for UTUC IVR time（month） Training cohort n=76（%） validation cohort n=32（%） Total n=108（%） ≤12 48（63.2） 23（71.9） 71（65.7） ＞12and≤36 22（28.9） 6（18.8） 28（25.9） ＞36 6（7.9） 3（9.3） 9（8.4） Cox regression analyses In an attempt to explore independent risk factors of IVR after RNU, we performed univariate and multivariate Cox regression analyses on training cohort. Specifically speaking , the univariate Cox regression analysis showed that hydronephrosis (P＜0.001), the history of bladder cancer (P＜0.001), ureteroscope (P＜0.001), tumor grade (P=0.006), and tumor margin (p＜0.001) were risk factors for RNU; and the multivariate one evinced that hydronephrosis (P＜0.010),the history of bladder cancer (P=0.005), ureteroscope (P=0.002),tumor grade (P=0.014), and tumor margin (p=0.006) were independent risk factors for IVR(Table 3). Table 3Univariate and multivariate analyses of variables associated with IVR in the training cohort variables Univariate analysis Multivariate analysis HR 95%CI P HR 95%CI P Gender Male Female Age ＜65y ≥65y BMI（kg/m²） ＜18.5 ≥18.5and＜24 ≤24 Hypertension Yes No Diabetes Yes No Hydronephrosis Yes No Hematuresis yes no The history of Bladder cancer Yes no Ureteroscope yes no Surgical method open Transabdominal laparoscope Retroperitoneal laparoscope Robot-assisted The location of tumour pelvis ureter both T-stage Tis/Ta/T1 T2/T3/T4 Lymph node status pN0/pNx pN+ Grade Low High Margin Yes No Ref 1.044 Ref 1.469 Ref 1.160 1.556 Ref 0.660 Ref 0.767 Ref 0.359 Ref 1.010 Ref 0.365 Ref 0.439 Ref 1.357 0.995 1.055 Ref 0.652 1.040 Ref 1.377 Ref 0.992 Ref 2.658 Ref 0.249 0.664-1.641 0.918-2.351 0.353-3.817 0.971-2.495 0.412-1.057 0.382-1.539 0.209-0.615 0.606-1.684 0.226-0.589 0.276-0.698 0.323-5.707 0.296-3.349 0.326-3.414 0.272-1.559 0.439-2.460 0.802-2.362 0.494-1.990 1.324-5.334 0.144-0.428 0.852 0.109 0.181 0.807 0.066 0.084 0.455 ＜0.001 0.968 ＜0.001 ＜0.001 0.941 0.677 0.994 0.929 0.138 0.336 0.929 0.246 0.136 0.006 ＜0.001 Ref 0.480 Ref 0.495 Ref 0.447 Ref 2.437 Ref 0.447 0.274-0.841 0.303-0.809 0.252-0.794 1.201-4.945 0.252-0.794 0.010 0.005 0.002 0.014 0.006 Development of the nomogram for IVR We constructed the nomogram based on the results of the training set Cox multivariate analysis. The nomogram for predicting IVR is shown in Fig 1. At the top of the nomogram, a scale provides a score for each prognostic variable. According to the sum of all scores axis at the bottom of the nomogram, probabilities of 1-, 3-,5-,and 8-year IVRFS were able to be estimated. Validation of the nomogram for IVR To validate the accuracy and predictive ability of the nomogram, we used time-dependent ROC analysis and C-index . The C-index for IVRFS were 0.722 in the training cohort and 0.767 in validation cohort. In the training cohort, the AUC values for 1-, 3-, and 5-year IVRFS were 0.743, 0.752, and 0.785, respectively. while in the validation cohort, they were 0.786, 0.826, and 0.813(Fig 2). the area under the AUC values of the IVRFS nomogram and the individual variables were compared between the training and validation cohort at 5-year. The results of this study revealed that the 5-year AUC value for nomogram was signifcantly higher than the individual variables (Fig 3). These results indicated that the nomogram provides a good discriminatory performance. In addition, the decision curves (DCA) showed the nomogram model curve located above the individual variable curve, indicating that the nomogram model made a better prediction (Fig 4). The calibration curves revealed that the IVR predicted by the nomogram was consistent with the actual observation results (Fig 5). Finally, we divided the patients in the validation cohort into two groups (high and low scores) based on the nomogram scores constructed from the training cohort, and observed that shorter IVRFS in the high-risk group than in the low-risk group in the training and validation cohort (Fig 6). Discussion As a relatively rare malignant tumor, the treatment of UTUC has made great progress in recent years. Further in-depth study about UTUC is still in urgent need given its high invasion and poor prognosis. The high incidence of incurrence recurrence after RNU is a characteristic of UTUC, which has a significant impact on the survival outcome of patients [ 14 ] . In recent years, predictive models have played an increasingly important role in personalized clinical treatment, and many risk stratifcation scores and nomograms have been developed to achieve optimal tumor management. Ishioka et al. built a risk stratifcation model for IVR based on patients with UTUC at 13 institutions in Japan, But the prediction performance is poor with a C-index of 0.600 [ 15 ] . Xylinas et al. built a model based on a larger population with 1839 patients, but the predictors are not signifcantly associated with IVR in external validation, which reduced the calibration of nomograms [ 11 ] . Zhang et al. built a model based on single center data [ 16 ] . Therefore, we conducted this study to develop a model to predict IVR in Chinese patients form multi-center. In our study, the rate of IVR after RNU were approximately 20.9% in training group and 21.1% in validation group. which was lower than the rates reported in previous studies [ 17 ] . The reason for this discrepancy may be that some patients underwent intravesical chemical instillation after RNU. 48 patients (63.2%) and 23 patients (71.9%) developed IVR within 1 year after RNU in the training and validation cohort, respectively. The result predicts that the peak of IVR is within 1 year after RNU, which is consistent with the study of Yamashita et al [ 18 ] . This also reminds us to strengthen the endoscopic surveillance after RNU. This model ultimately retained five predictors with good discrimination, calibration and clinical net benefit: ureteroscope, hydronephrosis, the history of bladder cancer, tumor grade and tumor margin. Diagnostic ureteroscope (URS) has the advantage to offer a direct view of the tumor for biopsy and to facilitate selective ureteric sampling for cytology in situ. In recent years, the risk of IVR after URS prior to RNU has been argued. Ishikawa et al. observed a similar rate of IVR at the 2-year follow-up (60% compared to 58.7%) in patients who underwent URS prior to RNU and controls [ 19 ] . Similar results were reported by Lee et al [ 20 ] . However Guo et al. found that IVR rates were lower in patients without a history of bladder cancer who underwent URS (HR 1.81) by meta-analysis, which is consistent with the results of our study [ 21 ] . The hypothesis is that the manipulation of the URS and the flow of irrigation could potentially elevate the risk of dissemination. Audenet et al. showed that the majority of bladder tumor following RNU are clonally related, which supports the notion that IVR is a result of neoplastic cell implantation rather than a distinct primary tumor [ 22 ] . Therefore, the diagnostic URS should not be routine and primary. Our study found the history of bladder cancer is strongly related to IVR. And the result was consistent with a meta-analysis of Seisen et al. [ 23 ] . The meta-analysis demonstrated that previous bladder cancer (HR 1.96, 95% CI 1.73–2.22; P < 0.001) is a significant predictor of IVR. Some studies also were congruent with the conclusions [ 24 , 25 ] . The result supported the notion that metachronous urothelial carcinomas, arising from either the upper or lower urinary tract, may stem from distinct transformed cells with unique genetic mutations [ 26 ] . The histological grade of the tumor is one of the more recognised factors influencing the prognosis of patients with UTUC. However, the influence of histological grade on IVR after RNU is quite controversial in different studies; Fang et al. proposed that low grade patients were more likely to have IVR, they suggested that it was related to the poor prognosis of high grade patients, some high-grade patients had died before the occurrence of IVR [ 27 ] . However, Zhu et al. suggested that high grade is more likely to cause recurrence [ 28 ] ,Consistent with the latter study, our study found pathological high grade to be an independent risk factor for IVR after RNU. We guess that this may be related to the greater susceptibility of high grade tumor cells to undergo intraepithelial spread. Sato et al. found that in UTUC patients without previous history or concurrent bladder tumors, positive surgical margins were an independent risk factor for IVR [ 29 ] . Another multicenter retrospective study including 485 patients with no previous history of bladder tumors showed that postive surgical margin was 3.3 times IVR risk for negative margin, The difference was statistically significant [ 8 ] . Our finding also showed that a positive surgical margin was an independent risk factor for IVR after RNU (P = 0.006), which is consistent with the above study. The surgical margin is positive, meaning that there are residual tumor cells, and these tumor cells may proliferate and invade and lead to IVR. Therefore, measures to prevent IVR should be actively taken in patients with positive surgical margins. In general, the presence of ureteral tumors could result in a gradual blockage in the ureter, eventually leading to the development of hydronephrosis, and the presence of hydronephrosis indicates that the tumor is large or extensive. Persistent obstruction leads to renal function damage; therefore, the degree of obstruction may be related to the tumor stage [ 30 ] . The meta-analysis of Ye et al. showed that preoperative hydronephrosis was significantly associated with worse OS (P = 0.004), CSS (P < 0.001), and DFS (P = 0.005), but not IVRFS (P = 0.12) [ 31 ] . When it comes to the present study, our results clarified that preoperative hydronephrosis is an independent risk factor for IVR. This result was confirmed in the study of Zhao et al [ 24 ] . The relationship between hydronephrosis and worse tumor outcome remains a mystery, suggesting that hydronephrosis might lead to the expansion and thinning of the ureter or renal pelvis wall, potentially aiding in the spread of cancer cells to nearby or distant organs. It could also result in an increased pressure causing reverse flow in lymphatics and blood vessels, thus promoting cancer dissemination. In addition, hydronephrosis is easy to cause impaired renal function and these patients can not receive adjuvant chemotherapy, which may also lead to IVR [ 32 ] . The specific relationship between hydronephrosis and IVR needs further study. The advantage of this study is that the follow-up was relatively long and the sample size was relative large compared to previous studies, in addition, the nomogram performed well in external validation, thus making the research results substantially credible. But there are several limitations to the study that should be acknowledged. First, the study was a retrospective study that may have caused inherent selection bias. Second, this nomogram was constructed based on the data from one province in china and more medical centers are needed to validate the generalizability of the model. Conclusions Our study suggested that ureteroscopy, hydronephrosis, the history of bladder cancer, positive surgical margin, and pathological high grade were independent risk factors for IVR after RNU. A reliable nomogram was developed based on risk factors to predict the probability of IVR in patients with UTUC after RNU, which can assist clinicians in assessing individualized IVR rates and making optimal treatment decisions. Declarations Ethical approval and informed consent : The study was conducted according to the guidelines of the Declaration of Helsinki. This research is a retrospective study and involves research in humans. The study passed the ethical review of the Lanzhou University Second Hospital (2023A-116). The above results are indicated in the statement at the end of the manuscript. Author Contribution Conceptualization: CW, Methodology: CW, Validation: BZ and ZMK, Formal Analysis:CW, Data Curation:SZO,JHW,HPL, Writing-Original Draft Preparation:CW, Writing-Review & Editing: PFS. All authors have read and agreed to the published version of the manuscript. Data Availability The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. References SIEGEL, R. L. et al. Cancer Statistics, 2021 [J]. Cancer J. Clin. 71 (1), 7–33 (2021). ROUPRêT, M. et al. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2023 Update [J]. Eur. Urol. 84 (1), 49–64 (2023). XYLINAS, E. & RINK, M. Multifocal carcinoma in situ of the upper tract is associated with high risk of bladder cancer recurrence [J]. Eur. Urol. 61 (5), 1069–1070 (2012). SORIA, F. et al. Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC) [J]. World J. 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Med. Association = Taiwan. yi zhi . 113 (11), 820–827 (2014). ZHU, J. & ZHANG, X. Risk Factors for Unfavorable Pathological Types of Intravesical Recurrence in Patients With Upper Urinary Tract Urothelial Carcinoma Following Radical Nephroureterectomy [J]. Front. Oncol. 12 , 834692 (2022). SATO, G. et al. Preoperative Pyuria Predicts for Intravesical Recurrence in Patients With Urothelial Carcinoma of the Upper Urinary Tract After Radical Nephroureterectomy Without a History of Bladder Cancer [J]. Clin. Genitourin. Cancer . 18 (2), e167–e173 (2020). MESSER, J. C. et al. Multi-institutional validation of the ability of preoperative hydronephrosis to predict advanced pathologic tumor stage in upper-tract urothelial carcinoma [J]. Urol. Oncol. 31 (6), 904–908 (2013). YE, T. et al. Prognostic Value of Preoperative Hydronephrosis in Patients Undergoing Radical Nephroureterectomy for Upper Tract Urinary Carcinoma: A Systematic Review and Meta-Analysis [J]. Front. Oncol. 10 , 600511 (2020). CHUNG P H 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 [J]. Urol. Oncol. 32 (7), 981–988 (2014). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5094557","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":381212040,"identity":"62c0ab4c-4744-44ed-9a46-ff53a4fef836","order_by":0,"name":"cheng wang","email":"","orcid":"","institution":"Lanzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"cheng","middleName":"","lastName":"wang","suffix":""},{"id":381212043,"identity":"0d2a669d-5cc2-400e-8dc6-d9d0641a8715","order_by":1,"name":"biao zhang","email":"","orcid":"","institution":"Lanzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"biao","middleName":"","lastName":"zhang","suffix":""},{"id":381212047,"identity":"c272a288-2799-409f-a135-3c0e18a69d5b","order_by":2,"name":"ziming kang","email":"","orcid":"","institution":"Lanzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"ziming","middleName":"","lastName":"kang","suffix":""},{"id":381212049,"identity":"3ba88970-bce8-40e6-9170-273d21d5ee1a","order_by":3,"name":"shuzhen ou","email":"","orcid":"","institution":"Lanzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"shuzhen","middleName":"","lastName":"ou","suffix":""},{"id":381212050,"identity":"37f5ff58-398d-414e-ac3b-ae71fb3a8c1e","order_by":4,"name":"pingheng li","email":"","orcid":"","institution":"Lanzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"pingheng","middleName":"","lastName":"li","suffix":""},{"id":381212051,"identity":"62fb9f37-47f3-4a7a-b94b-30c63a5756ec","order_by":5,"name":"jianghou wan","email":"","orcid":"","institution":"Lanzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"jianghou","middleName":"","lastName":"wan","suffix":""},{"id":381212052,"identity":"e723a824-09e7-405a-bfc9-d6b8d2b7ae65","order_by":6,"name":"panfeng shang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYDACCTApJ8cHptmI12JszEaylsQ2orXIz25+9vDrDoP0Nv4zBgwfyg4z8M9uwK/F4M4xc2PZMwa5bQxnDBhnnDvMIHHnAAEtEglm0pJtf3LbGHsMmHnbDoNECDhsRvo3oBaDdDZmHgPmv8RoYbiRYyb5sc0ggY0NqIWRGC0GN3LKpBnPGBi28bAVHOw5l84jcYOww7ZJ/txhIM/Pf3jjgx9l1nL8Mwg5DAiYeRsgjANAzENYPRAw/mwgSt0oGAWjYBSMVAAAStk8TMeWG1wAAAAASUVORK5CYII=","orcid":"","institution":"Lanzhou University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"panfeng","middleName":"","lastName":"shang","suffix":""}],"badges":[],"createdAt":"2024-09-16 02:08:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5094557/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5094557/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":71475460,"identity":"80d0e37b-4c42-4681-92cd-3ee9337f4a2f","added_by":"auto","created_at":"2024-12-16 04:56:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":71244,"visible":true,"origin":"","legend":"\u003cp\u003eNomogram for predicting 1-,3-, and 5-year IVRFS\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5094557/v1/4afaabdb091fee3469dbfdf8.png"},{"id":71474057,"identity":"bce547d5-9362-4927-957b-2166d01f4127","added_by":"auto","created_at":"2024-12-16 04:40:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":65647,"visible":true,"origin":"","legend":"\u003cp\u003eNomogram ROC curves to predict 1-,3-, and 5-year IVRFS in the training cohort (A1)and validation cohort (A2)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5094557/v1/f37a99f2310d6dbff1ef4eed.png"},{"id":71474058,"identity":"a7146734-1d18-4865-bab9-f9fc13ddd4a5","added_by":"auto","created_at":"2024-12-16 04:40:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":76287,"visible":true,"origin":"","legend":"\u003cp\u003e5-year ROC curves for IVR in the training cohort (A3)and validation cohort(A4)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5094557/v1/42d4ced2899a9d8b7f1f552d.png"},{"id":71474062,"identity":"2eb182b2-d97c-4a26-9bcc-979917f3f296","added_by":"auto","created_at":"2024-12-16 04:40:43","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":73228,"visible":true,"origin":"","legend":"\u003cp\u003eThe decision curves in the training cohort (A5)and validation cohort(A6)\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5094557/v1/3bb26cbc8756c5376a3c0f0b.png"},{"id":71474072,"identity":"b8f290f7-3654-45df-95e6-310452a27f8b","added_by":"auto","created_at":"2024-12-16 04:40:43","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":54306,"visible":true,"origin":"","legend":"\u003cp\u003eThe calibration curves of nomogram at 1,3, and 5 years in the training cohort (a,b,c),\u003c/p\u003e\n\u003cp\u003eThe calibration curves of nomogram at 1,3, and 5 years in the validation cohort (d,e,f).\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-5094557/v1/913cbd9fe0e7f00c18540820.png"},{"id":71474069,"identity":"c8a999c5-bde2-4814-a84e-1e9626a214ac","added_by":"auto","created_at":"2024-12-16 04:40:43","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":54548,"visible":true,"origin":"","legend":"\u003cp\u003eThe Kaplan–Meier curves of nomogram in the training cohort (A7) and validation cohort (A8)\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-5094557/v1/da46d8cb1bb78035a95353ce.png"},{"id":72589451,"identity":"a5ccacb8-f228-4b60-bf90-ea87e015352b","added_by":"auto","created_at":"2024-12-30 06:54:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":954957,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5094557/v1/a4fbf507-6cdf-46e7-81d5-3fd45795fdf2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Development and validation of a predictive model for intravesical recurrence after radical nephroureterectomy： a multi-center study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eUrothelial carcinomas are the 6th most frequently diagnosed tumor in the developed countries and may be located in the lower genitourinary tract (urethra and bladder) or upper genitourinary tract (ureter and pyelocaliceal system)\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Upper tract urothelial carcinoma (UTUC) is a relatively rare entity, accounting for 5\u0026ndash;10% of all urothelial tumors. The estimated annual incidence is 2 cases per 100,000 in western countries\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.Radical nephroureterectomy (RNU) with bladder sleeve resection is the standard surgical treatment for UTUC, especially for high-risk patients. UTUC is more invasive and has a poor prognosis even after RNU and sleeve cystectomy in time, as 22% ~ 47% of patients still have an intravesical recurrence (IVR) during the follow-up period\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. IVR mostly occurred within the first year postoperatively\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Once IVR occurs, patients have to undergo additional adjuvant treatment, such as transurethral bladder tumor resection surgery and intravesical instillation chemotherapy\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Yamashita et al. also indicated that IVR may reduce the 5-year survival rate of patient\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Therefore, how to identify the risk factors of IVR after RNU early has become a hot research topic in recent years.\u003c/p\u003e \u003cp\u003eNow, some studies have reported that positive preoperative urine cytology, preoperative diagnostic ureteroscopic, tumor stage, grade, surgical method, lymphovascular invasion and other factors are independent risk factors for IVR after RNU\u003csup\u003e[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. However factors that reliably predict IVR have not been identified. Thus, how to leverage patient stratification tools to better identify patients who may have IVR at an early stage has become a timely issue to be addressed\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e .\u003c/p\u003e \u003cp\u003eXylinas et al. constructed prediction models based on a larger population from Western countries\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e; however, For the Chinese population, there are significant differences in race, dietary habits, lifestyle choices, and exposure to common carcinogenic factors, especially aristolochic acid, compared with patients in Western countries\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. The purpose of this study was to investigate risk factors for IVR in patients with UTUC, and we developed a nomogram and hope to assist the urologist to optimize clinical decision-making.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData acquisition\u003c/h2\u003e \u003cp\u003e This retrospective study was approved by the Medical Ethics Committee of the the first/Second Hospital of Lanzhou University and Gansu Provincial Hospital. Informed consent was obtained from all eligible participants in advance. The data involved in this retrospective study were collected prospectively from primary UTUC patients who underwent RNU in these center from 2012 to 2022.Inclusion criteria were: (1) patients with pathological diagnosis of UTUC; (2) patients with primary disease; (3) patients with unilateral disease; (4) patients with RNU combined with cystic sleeve resection;(5) patients with complete follow-up data. Exclusion criteria were: (1) patients with bilateral UTUC; (2) patients with no RNU combined with cystectomy; (3) patients with metastatic uroepithelial carcinoma.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eClinicopathological data\u003c/h3\u003e\n\u003cp\u003eWe collected the following clinicopathological features of patients for analysis: gender, age at the first diagnosis, body mass index (BMI), tumor laterality, pathologic tumor stage (pT), lymph node status, tumor grade, tumor size, tumor location, surgery margin positivity. Patients with previous history of hypertension, diabetes, and bladder cancer, preoperative urine cytology, presence of hydronephrosis on the affected side, diagnostic ureteroscopy. All resected tumor specimens were sent for pathological examination by senior pathologists. The pathologic tumor stage and grade were evaluated according to the 2009 International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) TNM classification system (Edge and Compton 2010) and the 2016 World Health Organization (WHO) grading system (Humphrey et al. 2016).\u003c/p\u003e \u003cp\u003eIn addition to the preoperative detailed baseline information, we also collected the intraoperative and postoperative outcomes of radical nephroureterectomy. The outcome during the operation includes the operation time, the amount of bleeding during the operation and whether there is damage to the surrounding organs. The postoperative outcome includes the recovery time of gastrointestinal function, the length of hospital stay, the occurrence of complications such as infection, urinary fistula, and the retention time of the drainage tube.\u003c/p\u003e\n\u003ch3\u003eFollow-up\u003c/h3\u003e\n\u003cp\u003eWe monitored patients every 3 months during the first 2 years after surgery and every 6 months thereafter until 5 years. Follow-up assessments encompassed blood analyses, cystoscopy, ultrasound imaging of the urinary system, CT scans of the chest and abdomen, urine cytology, and urography procedures. When necessary, a bone scan, PET/CT or MRI examination was selectively carried out. Intravesical recurrence-free survival (IVRFS) was defined as the time from the date of RNU to the date of the first recurrence on imaging examination.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003ePatients of The Second Hospital of Lanzhou University Hospital were enrolled in the training cohort and validated in the cohort of The First Hospital of Lanzhou University Hospital and Gansu Provincial Hospital. Prognostic risk factors related to IVR were assessed by univariate and multivariate Cox regression analyses models in the training cohort, the multivariate Cox regression results were then integrated into the nomogram. The 1-/3-/5-/8-year IVRFS probabilities were estimated using the nomogram. Receiver operating characteristic (ROC) analyses were conducted in both cohorts, and the area under the ROC curve (AUC) and concordance index (C-index) were used to evaluate discrimination ability. To validate the accuracy of the model, calibration curves were drawn from 1000 bootstrap samples from the training and validation cohorts. All p-values were obtained from two-sided tests, and p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicated that the difference was statistically significant. R software (Version 4.3.2) and IBM SPSS Statistics (Version 26) were utilized to complete all statistical analyses and figures.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003ch3\u003eCharacteristics of patients and disease\u003c/h3\u003e\n\u003cp\u003eA cohort of 515 patients who met the specified inclusion and exclusion criteria were included in the study, with 363 patients in the training cohort and 152 patients in the validation cohort. The demographic and clinicopathological variables are summarized in Table 1.There were no significant diferences between the two cohorts except for age, ureteroscope, The location of tumour, grade. In the training cohort ,76 patients (20.9%) developed IVR after RNU, of which 48 patients (63.2%) developed IVR within 1 year after RNU, 22 patients (28.9%) developed IVR in 1-3 years (\u0026gt;1 year and \u0026le;3 years) after RNU, and others had IVR more than 3 years. In the validation cohort , 32 patients (21.1%) developed IVR after RNU, of which 23 patients (71.9%) developed IVR within 1 year after RNU, 6 patients (18.8%) developed IVR in 1-3 years (\u0026gt;1 year and \u0026le;3 years) after RNU, and others had IVR more than 3 years(Table 2).\u003c/p\u003e\n\u003cp\u003eTable 1\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eBasic clinical characteristics of patients with UTUC\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 41.2319%;\"\u003e\n \u003cp\u003evariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.9855%;\"\u003e\n \u003cp\u003eTraining cohort\u003c/p\u003e\n \u003cp\u003en=363（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.3383%;\"\u003e\n \u003cp\u003evalidation cohort\u003c/p\u003e\n \u003cp\u003en=152（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.3933%;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 41.2319%;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cp\u003e＜65y\u003c/p\u003e\n \u003cp\u003e\u0026ge;65y\u003c/p\u003e\n \u003cp\u003eBMI（kg/m\u0026sup2;）\u003c/p\u003e\n \u003cp\u003e＜18.5\u003c/p\u003e\n \u003cp\u003e\u0026ge;18.5and＜24\u003c/p\u003e\n \u003cp\u003e\u0026le;24\u003c/p\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eHydronephrosis\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eHematuresis\u003c/p\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003cp\u003eThe history of Bladder cancer\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003cp\u003eUreteroscope\u003c/p\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003cp\u003eSurgical method\u003c/p\u003e\n \u003cp\u003eopen\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;laparoscope\u003c/p\u003e\n \u003cp\u003eRobot-assisted\u003c/p\u003e\n \u003cp\u003eThe location of tumour\u003c/p\u003e\n \u003cp\u003epelvis\u003c/p\u003e\n \u003cp\u003eureter\u003c/p\u003e\n \u003cp\u003eboth\u003c/p\u003e\n \u003cp\u003eT-stage\u003c/p\u003e\n \u003cp\u003eTis/Ta/T1\u003c/p\u003e\n \u003cp\u003eT2/T3/T4\u003c/p\u003e\n \u003cp\u003eLymph node status\u003c/p\u003e\n \u003cp\u003epN0/pNx\u003c/p\u003e\n \u003cp\u003epN+\u003c/p\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003cp\u003eMargin\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eIVR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.9855%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e206（56.7）\u003c/p\u003e\n \u003cp\u003e157（43.3）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e150（41.3）\u003c/p\u003e\n \u003cp\u003e213（58.7）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18（5）\u003c/p\u003e\n \u003cp\u003e177（48.7）\u003c/p\u003e\n \u003cp\u003e168（46.3）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e106（29.2）\u003c/p\u003e\n \u003cp\u003e257（70.8）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e36（9.9）\u003c/p\u003e\n \u003cp\u003e327（90.1）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e214（59.0）\u003c/p\u003e\n \u003cp\u003e149（41.0）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e264（72.7）\u003c/p\u003e\n \u003cp\u003e99（27.3）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e62（17.1）\u003c/p\u003e\n \u003cp\u003e301（82.9）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e81（22.3）\u003c/p\u003e\n \u003cp\u003e282（77.7）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18（5）\u003c/p\u003e\n \u003cp\u003e325（89.5）\u003c/p\u003e\n \u003cp\u003e20（5.5）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e188（51.8）\u003c/p\u003e\n \u003cp\u003e150（41.3）\u003c/p\u003e\n \u003cp\u003e25（6.9）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e94（25.9）\u003c/p\u003e\n \u003cp\u003e269（74.1）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e314（86.5）\u003c/p\u003e\n \u003cp\u003e49（13.5）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e83（22.9）\u003c/p\u003e\n \u003cp\u003e280（77.1）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32（8.8）\u003c/p\u003e\n \u003cp\u003e331（91.2）\u003c/p\u003e\n \u003cp\u003e76（20.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.3383%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e80（52.6）\u003c/p\u003e\n \u003cp\u003e72（47.4）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e48（31.6）\u003c/p\u003e\n \u003cp\u003e104（68.4）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13（8.6）\u003c/p\u003e\n \u003cp\u003e81（53.2）\u003c/p\u003e\n \u003cp\u003e58（38.2）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e51（33.6）\u003c/p\u003e\n \u003cp\u003e101（66.4）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10（6.6）\u003c/p\u003e\n \u003cp\u003e142（93.4）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e81（53.3）\u003c/p\u003e\n \u003cp\u003e71（46.7）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e112（73.7）\u003c/p\u003e\n \u003cp\u003e40（26.3）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31（20.4）\u003c/p\u003e\n \u003cp\u003e121（79.6）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e56（36.8）\u003c/p\u003e\n \u003cp\u003e96（63.2）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13（8.6）\u003c/p\u003e\n \u003cp\u003e135（88.8）\u003c/p\u003e\n \u003cp\u003e4（2.6）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e57（37.5）\u003c/p\u003e\n \u003cp\u003e82（53.9）\u003c/p\u003e\n \u003cp\u003e13（8.6）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e44（28.9）\u003c/p\u003e\n \u003cp\u003e108（71.1）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e140（92.1）\u003c/p\u003e\n \u003cp\u003e12（7.9）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e57（37.5）\u003c/p\u003e\n \u003cp\u003e95（62.5）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6（3.9）\u003c/p\u003e\n \u003cp\u003e146（96.1）\u003c/p\u003e\n \u003cp\u003e32（21.1）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.3933%;\"\u003e\n \u003cp\u003e0.391\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.328\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.226\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.236\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.823\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.372\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.476\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.774\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2 The time characteristics of IVR after RNU for UTUC\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36.5942%;\"\u003e\n \u003cp\u003eIVR time（month）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5521%;\"\u003e\n \u003cp\u003eTraining cohort\u003c/p\u003e\n \u003cp\u003en=76（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7088%;\"\u003e\n \u003cp\u003evalidation cohort\u003c/p\u003e\n \u003cp\u003en=32（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003en=108（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36.5942%;\"\u003e\n \u003cp\u003e\u0026le;12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5521%;\"\u003e\n \u003cp\u003e48（63.2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7088%;\"\u003e\n \u003cp\u003e23（71.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e71（65.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36.5942%;\"\u003e\n \u003cp\u003e＞12and\u0026le;36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5521%;\"\u003e\n \u003cp\u003e22（28.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7088%;\"\u003e\n \u003cp\u003e6（18.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e28（25.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36.5942%;\"\u003e\n \u003cp\u003e＞36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5521%;\"\u003e\n \u003cp\u003e6（7.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.7088%;\"\u003e\n \u003cp\u003e3（9.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e9（8.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch3\u003eCox regression analyses\u003c/h3\u003e\n\u003cp\u003eIn an attempt to explore independent risk factors of IVR after RNU, we performed univariate and multivariate Cox regression analyses on training cohort. Specifically speaking , the univariate Cox regression analysis showed that hydronephrosis (P＜0.001), the history of bladder cancer (P＜0.001), ureteroscope (P＜0.001), tumor grade (P=0.006), and tumor margin (p＜0.001) were risk factors for RNU; and the multivariate one evinced that hydronephrosis (P＜0.010),the history of bladder cancer (P=0.005), ureteroscope (P=0.002),tumor grade (P=0.014), and tumor margin (p=0.006) were independent risk factors for IVR(Table 3).\u003c/p\u003e\n\u003cp\u003eTable 3Univariate and multivariate analyses of variables associated with IVR in the training cohort\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 184px;\"\u003e\n \u003cp\u003evariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 211px;\"\u003e\n \u003cp\u003eUnivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eMultivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 184px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cp\u003e＜65y\u003c/p\u003e\n \u003cp\u003e\u0026ge;65y\u003c/p\u003e\n \u003cp\u003eBMI（kg/m\u0026sup2;）\u003c/p\u003e\n \u003cp\u003e＜18.5\u003c/p\u003e\n \u003cp\u003e\u0026ge;18.5and＜24\u003c/p\u003e\n \u003cp\u003e\u0026le;24\u003c/p\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eHydronephrosis\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eHematuresis\u003c/p\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003cp\u003eThe history of Bladder cancer\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003cp\u003eUreteroscope\u003c/p\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003cp\u003eSurgical method\u003c/p\u003e\n \u003cp\u003eopen\u003c/p\u003e\n \u003cp\u003eTransabdominal laparoscope\u003c/p\u003e\n \u003cp\u003eRetroperitoneal laparoscope\u003c/p\u003e\n \u003cp\u003eRobot-assisted\u003c/p\u003e\n \u003cp\u003eThe location of tumour\u003c/p\u003e\n \u003cp\u003epelvis\u003c/p\u003e\n \u003cp\u003eureter\u003c/p\u003e\n \u003cp\u003eboth\u003c/p\u003e\n \u003cp\u003eT-stage\u003c/p\u003e\n \u003cp\u003eTis/Ta/T1\u003c/p\u003e\n \u003cp\u003eT2/T3/T4\u003c/p\u003e\n \u003cp\u003eLymph node status\u003c/p\u003e\n \u003cp\u003epN0/pNx\u003c/p\u003e\n \u003cp\u003epN+\u003c/p\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003cp\u003eMargin\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e1.044\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e1.469\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e1.160\u003c/p\u003e\n \u003cp\u003e1.556\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.660\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.767\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.359\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e1.010\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.365\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.439\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e1.357\u003c/p\u003e\n \u003cp\u003e0.995\u003c/p\u003e\n \u003cp\u003e1.055\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.652\u003c/p\u003e\n \u003cp\u003e1.040\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e1.377\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.992\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e2.658\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.664-1.641\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.918-2.351\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.353-3.817\u003c/p\u003e\n \u003cp\u003e0.971-2.495\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.412-1.057\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.382-1.539\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.209-0.615\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.606-1.684\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.226-0.589\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.276-0.698\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.323-5.707\u003c/p\u003e\n \u003cp\u003e0.296-3.349\u003c/p\u003e\n \u003cp\u003e0.326-3.414\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.272-1.559\u003c/p\u003e\n \u003cp\u003e0.439-2.460\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.802-2.362\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.494-1.990\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.324-5.334\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.144-0.428\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.852\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.109\u003c/p\u003e\n \u003cp\u003e0.181\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.807\u003c/p\u003e\n \u003cp\u003e0.066\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.084\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.455\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.968\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003cp\u003e0.941\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.677\u003c/p\u003e\n \u003cp\u003e0.994\u003c/p\u003e\n \u003cp\u003e0.929\u003c/p\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.336\u003c/p\u003e\n \u003cp\u003e0.929\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.246\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.136\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.480\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.495\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.447\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e2.437\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003cp\u003e0.447\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.274-0.841\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.303-0.809\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.252-0.794\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.201-4.945\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.252-0.794\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch3\u003eDevelopment of the nomogram for IVR\u003c/h3\u003e\n\u003cp\u003eWe constructed the nomogram based on the results of the training set Cox multivariate analysis. The nomogram for predicting IVR is shown in Fig 1. At the top of the nomogram, a scale provides a score for each prognostic variable. According to the sum of all scores axis at the bottom of the nomogram, probabilities of 1-, 3-,5-,and 8-year IVRFS were able to be estimated.\u0026nbsp;\u003c/p\u003e\u003ch3\u003eValidation of the nomogram for IVR\u003c/h3\u003e\n\u003cp\u003eTo validate the accuracy and predictive ability of the nomogram, we used time-dependent ROC analysis and C-index . The C-index for IVRFS were 0.722 in the training cohort and 0.767 in validation cohort. In the training cohort, the AUC values for 1-, 3-, and 5-year IVRFS were 0.743, 0.752, and 0.785, respectively. while in the validation cohort, they were 0.786, 0.826, and 0.813(Fig 2). the area under the AUC values of the IVRFS nomogram and the individual variables were compared between the training and validation cohort at 5-year. The results of this study revealed that the 5-year AUC value for nomogram was signifcantly higher than the individual variables (Fig 3). These results indicated that the nomogram provides a good discriminatory performance. In addition, the decision curves (DCA) showed the nomogram model curve located above the individual variable curve, indicating that the nomogram model made a better prediction (Fig 4). The calibration curves revealed that the IVR predicted by the nomogram was consistent with the actual observation results (Fig 5). Finally, we divided the patients in the validation cohort into two groups (high and low scores) based on the nomogram scores constructed from the training cohort, and observed that shorter IVRFS in the high-risk group than in the low-risk group in the training and validation cohort (Fig 6).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAs a relatively rare malignant tumor, the treatment of UTUC has made great progress in recent years. Further in-depth study about UTUC is still in urgent need given its high invasion and poor prognosis. The high incidence of incurrence recurrence after RNU is a characteristic of UTUC, which has a significant impact on the survival outcome of patients\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. In recent years, predictive models have played an increasingly important role in personalized clinical treatment, and many risk stratifcation scores and nomograms have been developed to achieve optimal tumor management. Ishioka et al. built a risk stratifcation model for IVR based on patients with UTUC at 13 institutions in Japan, But the prediction performance is poor with a C-index of 0.600\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Xylinas et al. built a model based on a larger population with 1839 patients, but the predictors are not signifcantly associated with IVR in external validation, which reduced the calibration of nomograms\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Zhang et al. built a model based on single center data\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Therefore, we conducted this study to develop a model to predict IVR in Chinese patients form multi-center.\u003c/p\u003e \u003cp\u003eIn our study, the rate of IVR after RNU were approximately 20.9% in training group and 21.1% in validation group. which was lower than the rates reported in previous studies\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. The reason for this discrepancy may be that some patients underwent intravesical chemical instillation after RNU. 48 patients (63.2%) and 23 patients (71.9%) developed IVR within 1 year after RNU in the training and validation cohort, respectively. The result predicts that the peak of IVR is within 1 year after RNU, which is consistent with the study of Yamashita et al\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. This also reminds us to strengthen the endoscopic surveillance after RNU. This model ultimately retained five predictors with good discrimination, calibration and clinical net benefit: ureteroscope, hydronephrosis, the history of bladder cancer, tumor grade and tumor margin.\u003c/p\u003e \u003cp\u003eDiagnostic ureteroscope (URS) has the advantage to offer a direct view of the tumor for biopsy and to facilitate selective ureteric sampling for cytology in situ. In recent years, the risk of IVR after URS prior to RNU has been argued. Ishikawa et al. observed a similar rate of IVR at the 2-year follow-up (60% compared to 58.7%) in patients who underwent URS prior to RNU and controls\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Similar results were reported by Lee et al\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. However Guo et al. found that IVR rates were lower in patients without a history of bladder cancer who underwent URS (HR 1.81) by meta-analysis, which is consistent with the results of our study\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. The hypothesis is that the manipulation of the URS and the flow of irrigation could potentially elevate the risk of dissemination. Audenet et al. showed that the majority of bladder tumor following RNU are clonally related, which supports the notion that IVR is a result of neoplastic cell implantation rather than a distinct primary tumor \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Therefore, the diagnostic URS should not be routine and primary.\u003c/p\u003e \u003cp\u003eOur study found the history of bladder cancer is strongly related to IVR. And the result was consistent with a meta-analysis of Seisen et al.\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. The meta-analysis demonstrated that previous bladder cancer (HR 1.96, 95% CI 1.73\u0026ndash;2.22; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) is a significant predictor of IVR. Some studies also were congruent with the conclusions\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. The result supported the notion that metachronous urothelial carcinomas, arising from either the upper or lower urinary tract, may stem from distinct transformed cells with unique genetic mutations \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe histological grade of the tumor is one of the more recognised factors influencing the prognosis of patients with UTUC. However, the influence of histological grade on IVR after RNU is quite controversial in different studies; Fang et al. proposed that low grade patients were more likely to have IVR, they suggested that it was related to the poor prognosis of high grade patients, some high-grade patients had died before the occurrence of IVR\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. However, Zhu et al. suggested that high grade is more likely to cause recurrence\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e ,Consistent with the latter study, our study found pathological high grade to be an independent risk factor for IVR after RNU. We guess that this may be related to the greater susceptibility of high grade tumor cells to undergo intraepithelial spread.\u003c/p\u003e \u003cp\u003eSato et al. found that in UTUC patients without previous history or concurrent bladder tumors, positive surgical margins were an independent risk factor for IVR\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. Another multicenter retrospective study including 485 patients with no previous history of bladder tumors showed that postive surgical margin was 3.3 times IVR risk for negative margin, The difference was statistically significant\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Our finding also showed that a positive surgical margin was an independent risk factor for IVR after RNU (P\u0026thinsp;=\u0026thinsp;0.006), which is consistent with the above study. The surgical margin is positive, meaning that there are residual tumor cells, and these tumor cells may proliferate and invade and lead to IVR. Therefore, measures to prevent IVR should be actively taken in patients with positive surgical margins.\u003c/p\u003e \u003cp\u003eIn general, the presence of ureteral tumors could result in a gradual blockage in the ureter, eventually leading to the development of hydronephrosis, and the presence of hydronephrosis indicates that the tumor is large or extensive. Persistent obstruction leads to renal function damage; therefore, the degree of obstruction may be related to the tumor stage\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. The meta-analysis of Ye et al. showed that preoperative hydronephrosis was significantly associated with worse OS (P\u0026thinsp;=\u0026thinsp;0.004), CSS (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and DFS (P\u0026thinsp;=\u0026thinsp;0.005), but not IVRFS (P\u0026thinsp;=\u0026thinsp;0.12)\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. When it comes to the present study, our results clarified that preoperative hydronephrosis is an independent risk factor for IVR. This result was confirmed in the study of Zhao et al\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. The relationship between hydronephrosis and worse tumor outcome remains a mystery, suggesting that hydronephrosis might lead to the expansion and thinning of the ureter or renal pelvis wall, potentially aiding in the spread of cancer cells to nearby or distant organs. It could also result in an increased pressure causing reverse flow in lymphatics and blood vessels, thus promoting cancer dissemination. In addition, hydronephrosis is easy to cause impaired renal function and these patients can not receive adjuvant chemotherapy, which may also lead to IVR\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. The specific relationship between hydronephrosis and IVR needs further study.\u003c/p\u003e \u003cp\u003eThe advantage of this study is that the follow-up was relatively long and the sample size was relative large compared to previous studies, in addition, the nomogram performed well in external validation, thus making the research results substantially credible. But there are several limitations to the study that should be acknowledged. First, the study was a retrospective study that may have caused inherent selection bias. Second, this nomogram was constructed based on the data from one province in china and more medical centers are needed to validate the generalizability of the model.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur study suggested that ureteroscopy, hydronephrosis, the history of bladder cancer, positive surgical margin, and pathological high grade were independent risk factors for IVR after RNU. A reliable nomogram was developed based on risk factors to predict the probability of IVR in patients with UTUC after RNU, which can assist clinicians in assessing individualized IVR rates and making optimal treatment decisions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthical approval and informed consent : The study was conducted according to the guidelines of the Declaration of Helsinki. This research is a retrospective study and involves research in humans. The study passed the ethical review of the Lanzhou University Second Hospital (2023A-116). The above results are indicated in the statement at the end of the manuscript.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: CW, Methodology: CW, Validation: BZ and ZMK, Formal Analysis:CW, Data Curation:SZO,JHW,HPL, Writing-Original Draft Preparation:CW, Writing-Review \u0026amp; Editing: PFS. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSIEGEL, R. L. et al. Cancer Statistics, 2021 [J]. \u003cem\u003eCancer J. Clin.\u003c/em\u003e \u003cb\u003e71\u003c/b\u003e (1), 7\u0026ndash;33 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eROUPR\u0026ecirc;T, M. et al. 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Oncol.\u003c/em\u003e \u003cb\u003e32\u003c/b\u003e (7), 981\u0026ndash;988 (2014).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"upper tract urothelial carcinoma, intravesical recurrence, risk factor, nomogram, Predictive model","lastPublishedDoi":"10.21203/rs.3.rs-5094557/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5094557/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe high incidence of incurrence recurrence(IVR) after radical nephroureterectomy (RNU) is a characteristic of upper urinary tract urothelial carcinoma (UTUC), which has a significant impact on the survival outcome of patients. This study aimed to construct nomogram using data from multicenter data to predict IVR in patients with UTUC.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eClinical data of 515 UTUC patients after RNU were gathered from three medical centers between 2012 and 2022. The factors associated with IVR were analyzed by univariate and multivariate Cox proportional risk models in one center as training cohort, and included independent risk factors into nomogram models predicting IVR-free survival (IVRFS). Another two centers were collected as the external cohort to validate the predictive accuracy and discriminative ability of the nomogram.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eUreteroscopy, hydronephrosis, the history of bladder cancer, surgical margin and tumor grade were associated with IVR after UTUC (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The C-index of the nomogram in the training cohort were 0.722. The C-index of the nomograms in the external validation cohort were 0.767.Receiver operating characteristic (ROC) curves, calibration curves, and survival curves all demonstrated good predictive performance of the nomogram.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eUreteroscopy, hydronephrosis, the history of bladder cancer, surgical margin and tumor grade can be used to independently predict IVR after RNU. The nomogram was built based on these factors had good differentiation and conformity, which can assist clinicians in assessing individualized IVR rates and making optimal treatment decisions.\u003c/p\u003e","manuscriptTitle":"Development and validation of a predictive model for intravesical recurrence after radical nephroureterectomy： a multi-center study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-16 04:40:38","doi":"10.21203/rs.3.rs-5094557/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fcf7b0a2-e295-455b-ac75-0c72df3efc0b","owner":[],"postedDate":"December 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":40603522,"name":"Health sciences/Oncology"},{"id":40603523,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2024-12-30T06:53:35+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-16 04:40:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5094557","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5094557","identity":"rs-5094557","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}