Long-term Functional and Oncological Outcomes after Radical Cystectomy with Orthotopic Neobladder: A single Institution Study

Long-term Functional and Oncological Outcomes after Radical Cystectomy with Orthotopic Neobladder: A single Institution 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 Research Article Long-term Functional and Oncological Outcomes after Radical Cystectomy with Orthotopic Neobladder: A single Institution Study shinji ohtake, Kan Koyama, Genya Iwamoto, Eren Iwasa, Jurii Karibe, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8781132/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 Background Radical cystectomy (RC) with orthotopic neobladder (ONB) reconstruction provides oncological control and quality-of-life benefits for selected patients with bladder cancer. However, prognostic factors for recurrence remain to be elucidated. Herein, we evaluated oncological outcomes after ONB reconstruction. Methods We retrospectively reviewed 84 patients who underwent RC with ONB reconstruction at our institution between June 2009 and August 2024. We analyzed clinicopathological characteristics, perioperative variables, and postoperative outcomes. Results All patients were male, the median age was 68 ± 7.2 years, and the median follow-up was 79 months (range, 4–179). The 5- and 10-year recurrence-free survival (RFS) rates were 76% and 72%, and the 5- and 10-year cancer-specific survival rates were 92% and 83%, respectively. In univariate analysis, postoperative nodal status, adjuvant chemotherapy, and postoperative T status were significantly associated with RFS. Multivariate analysis identified postoperative T status as the only independent predictor (HR 2.976, 95% CI 1.179–7.5132, p = 0.021). radical cystectomy orthotopic neobladder urethral recurrence urethral biopsy renal function Figures Figure 1 Figure 2 Introduction Radical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for muscle-invasive bladder cancer and selected high-risk non-muscle-invasive disease patients[1]. After RC, urinary diversion is required, with ileal conduit (IC) and orthotopic neobladder (ONB) being the most commonly utilized diversion types. IC is the standard approach because of its safety and oncological effectiveness[2]. ONB reconstruction has gained increasing acceptance in selected patients, as it offers potential improvements in body image and quality of life while maintaining acceptable oncological outcomes[3]. However, concerns remain regarding the long-term oncological safety and functional outcomes. In particular, whether orthotopic diversion compromises cancer control, increases the risk of urethral recurrence, or leads to progressive renal dysfunction remain to be elucidated, especially in real-world clinical settings with extended follow-up[4]. Previous studies have reported that long-term survival after RC is primarily determined by tumor-related factors rather than the type of urinary diversion and that ONB reconstruction achieves oncological outcomes comparable to incontinent diversion in selected patients[5,6]. In addition to oncological control, preservation of renal function is an important consideration after ONB reconstruction. Renal function is preserved in most patients; however, late deterioration has been observed, most commonly in association with postoperative hydronephrosis or upper urinary tract obstruction, independent of urinary diversion type[7–10]. Long-term single-institution data evaluating oncological control, urethral recurrence, and renal function simultaneously remain limited. The aim of the present study was to evaluate the long-term oncological and functional outcomes of patients undergoing RC with ONB reconstruction at a single institution. Specifically, we focused on recurrence patterns, urethral recurrence, and longitudinal changes in renal function to assess the overall safety and clinical validity of ONB reconstruction in routine practice. Materials & Methods Patient Selection We retrospectively reviewed the medical records of patients who underwent RC with ONB reconstruction for bladder cancer at Yokosuka Kyosai Hospital between June 2009 and August 2024. The criteria for selecting a urinary diversion at the time of RC were as follows. ONB reconstruction was selected for patients younger than 75 years who had no tumor involvement of the bladder neck and were expected to be capable of postoperative self-catheterization. Urethral biopsy prior to ONB creation was performed at the surgeon’s discretion, and ONB reconstruction was avoided in tumor-positive cases in urethral biopsy. IC diversion was selected for patients who were able to manage stoma care and pouch replacement independently regardless of tumor location. Cutaneous ureterostomy was selected for patients in whom bowel use was contraindicated due to factors such as severe adhesions, as well as for elderly patients or those with significant comorbidities and relatively limited tolerance for major surgery. A total of 84 consecutive patients were included in this study. All procedures were performed under the supervision of a single expert surgeon. Patients who had previously undergone urinary diversion and those with insufficient follow-up data were excluded. The study protocol was approved by the Institutional Review Board, and the requirement for informed consent was waived owing to the retrospective nature of the study (approval number: YKH22-55a). Data Collection Baseline characteristics, including sex, age, smoking history, and receipt of neoadjuvant chemotherapy (NAC), were recorded. Pathological findings were reviewed, including tumor stage, nodal status, presence of variant histology, and urethral and ureteral margin status. Postoperative adjuvant chemotherapy and recurrence patterns (local or distant) were documented. The primary oncological endpoint was PFS, defined as the time from surgery to disease recurrence. Recurrence was confirmed by radiographic or pathological evidence. Estimated glomerular filtration rate (eGFR) was calculated using the Japanese Society of Nephrology formula at baseline and every year after surgery. Renal function decline was defined as a reduction of ≥ 25% compared with preoperative eGFR one year after surgery. All postoperative complications (early [≤ 30 days] and late [> 30 days]) were graded using the Clavien–Dindo classification system, and the details were recorded. Statistical Analysis Survival curves were generated using the Kaplan–Meier method. Differences between groups were compared with the log-rank test. Univariate and multivariate analyses for PFS were performed using the Cox proportional hazards model, with results expressed as hazard ratios and 95% confidence intervals. Variables with p < 0.05 in univariate analysis were entered into the multivariate model. For renal function analysis, potential predictors, including age, preoperative eGFR, hydronephrosis, and urinary tract infection, were analyzed using univariate logistic regression. Variables with p < 0.05 were subsequently assessed by multivariate logistic regression. Significance was defined as a p value < 0.05. All analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Japan), a graphical user interface for R[11]. Results A total of 84 male patients who underwent RC with ONB reconstruction were included in the analysis. The median age was 68 ± 7.2 years. Forty-one patients (48.8%) had a history of smoking. NAC was administered in 36 patients (42.9%). Pathological examination revealed ≤ pT1 in 56, pT2 in 10, pT3 in 17, and pT4 in one patient. Nodal metastasis was detected in nine patients. Variant histology was present in nine cases. The bladder tumor locations were distributed as follows: posterior wall (n = 14), anterior wall (n = 5), trigone (n = 22), dome (n = 3), lateral wall (n = 10), ureteric orifice (n = 8), and overlapping lesion (n = 22) (Table 1). Short-term (within 30 days) complications occurred in 47.6% (40/84) of patients, consisting of Clavien Grade ≤ II in 32 patients and Grade III in eight. Long-term (beyond 30 days) complications occurred in 27.4% (23/84) of patients, consisting of Clavien Grade ≤ II in nine cases and Grade III in 14 (Table 2). The median follow-up was 79 months (range, 4–179). During follow-up, 21 patients experienced recurrence, including four local recurrences and 17 distant recurrences (lymph nodes in 12, lung in six, and liver in three). The median time to recurrence was 18.4 months (range, 2–87). The 5- and 10-year recurrence-free survival (RFS) rates were 76% and 72%, respectively. The 5- and 10-year cancer-specific survival (CSS) rates were 92% and 83%, respectively. Urethral recurrence was not observed in any patient, including those that did not undergo preoperative urethral biopsy (n = 63). The cutoff values were set at 3 for NLR, 4 g/dL for albumin, and 12 g/dL for hemoglobin based on previous studies[12–14]. In univariate Cox analysis, pathological T category (HR 3.635 95% CI 1.501–8.805, P < 0.001), pathological N category (HR 3.61, 95% CI 1.3–9.9, P = 0.0127), and receipt of adjuvant chemotherapy (HR 3.121, 95% CI 1.2–8.08, P = 0.019) were significantly associated with PFS. In multivariate analysis, only pathological T category remained significant (HR 2.976, 95% CI 1.18–7.51, P = 0.021). Median RFS was not reached in both groups; however, patients with pT ≥ 2 disease showed significantly worse RFS (log-rank P = 0.002) (Fig. 2 ). Median eGFR declined from 66.5 ± 15.6 mL/min/1.73 m² preoperatively to 52.3 ± 15.4 at 12 months, 54.4 ± 15.5 at 36 months, 54.2 ± 17 at 60 months, and 49.1 ± 14.4 at 120 months postoperatively (Fig. 1 ). When decline was defined as a ≥ 25% decrease from baseline one year after surgery, 22 of 78 patients (28.2%) showed decline. In univariate analyses, the presence of postoperative hydronephrosis was the only significant predictor of renal function decline (Table 3). Discussion In the present study, RC with ONB reconstruction was associated with favorable long-term oncological and functional outcomes, without apparent increases in recurrence, urethral recurrence, or severe renal deterioration. These findings support the oncological safety and clinical validity of ONB reconstruction in appropriately selected patients. Our oncological outcomes are comparable to those reported in contemporary large series. In a critical review of RC with ONB reconstruction, Stenzl et al. reported overall 5- and 10-year RFS rates of 62–68% and 50–66%, respectively, in patients with organ-confined disease[15]. Similarly, in a population-based analysis using the SEER database, Su et al. reported 5-year CSS probabilities of 55% for IC diversion and 72.9% for ONB diversion[5]. Cheng et al. reported favorable mid-term outcomes after robotic intracorporeal Studer neobladder reconstruction, with a 60-month cumulative RFS rate of 87.4%[16]. Our cohort demonstrated 5- and 10-year RFS rates of 76% and 72%, and 5- and 10-year CSS rates of 92% and 83%, respectively. Although differences in patient selection, baseline characteristics, and surgical approaches across studies must be considered, these findings suggest that the long-term oncological outcomes of our real-world ONB reconstruction population were similar to those reported in previous large-scale or contemporary series. This may partly reflect orthotopic diversion being typically offered to carefully selected patients with favorable clinical profiles. Several landmark studies, including the cohort reported by Stein et al., demonstrated that long-term survival after RC is primarily determined by tumor-related factors and that the type of urinary diversion does not independently compromise cancer control[17]. More recent population-based and multicenter studies have similarly reported that ONB reconstruction provides RFS and overall survival outcomes comparable to those of IC diversion when appropriate selection criteria are applied. In the present cohort, the overall recurrence rate and recurrence patterns were within the range reported in contemporary literature[5,15,16,18,19]. These real-world data with long-term follow-up further support the hypothesis that orthotopic diversion itself does not adversely affect oncological outcomes and should not be avoided solely because of concerns regarding cancer control. We explored the potential role of the NLR as a predictor of recurrence. In contrast to some previous reports[20,21], NLR was not significantly associated with oncological outcomes in our cohort and did not provide additional prognostic value, suggesting it should be interpreted cautiously in clinical decision-making. In contrast, Kawahara et al. reported that elevated preoperative NLR was an independent prognostic marker for cancer-specific mortality in a broader RC population, irrespective of diversion type[21]. This discrepancy may be attributable to differences in cohort composition, as our study focused exclusively on ONB reconstruction patients, a selected group with generally favorable baseline characteristics. Moreover, the limited sample size and low event rate in ONB reconstruction cohorts may have reduced the power to detect modest prognostic effects. Thus, the prognostic utility of NLR may vary depending on patient background and urinary diversion strategy. Urethral recurrence represents a specific oncological concern after RC, particularly in patients undergoing orthotopic diversion. A previous systematic review reported urethral recurrence rates ranging from approximately 1% to 14%, and identified various risk factors including multifocal disease, carcinoma in situ, bladder neck involvement, and prostatic urethral invasion[22]. Notably, in our cohort, no urethral recurrence was observed, including in patients who did not undergo routine preoperative urethral biopsy. Although careful patient selection remains essential, these findings suggest that urethral preservation without routine biopsy is oncologically acceptable in selected patients in real-world practice. Long-term renal function is a major concern following RC. Previous studies reported that postoperative renal deterioration is influenced predominantly by patient-related and obstructive factors rather than by the type of urinary diversion[9,23]. Similarly, a large retrospective cohort study of 670 patients reported that progression of chronic kidney disease (CKD) after RC was associated with preoperative hydronephrosis, adjuvant chemotherapy, comorbidity burden, and baseline renal function, whereas the type of urinary diversion was not identified as an independent risk factor[8]. Eisenberg et al., in a cohort with a median follow-up of 10 years, reported that the rate of renal function deterioration was similar between patients undergoing ONB reconstruction and those receiving IC diversion[24]. Furthermore, a propensity score-matched analysis comparing three urinary diversion techniques (ONB, IC, and cutaneous ureterostomy) demonstrated no significant difference in long-term eGFR decline between a neobladder group and those that received other diversion types[10]. These results support the hypothesis that postoperative renal outcomes are multifactorial and largely determined by preexisting conditions and perioperative factors. In particular, the presence of postoperative hydronephrosis was reported as a significant predictor of renal function decline after ONB reconstruction 8 . This finding underscores the importance of surgical technique and careful postoperative surveillance to prevent upper urinary tract obstruction. Several studies have reported longitudinal decline in renal function following RC. Hatakeyama et al. reported an approximate 15% decline in renal function over a five-year follow-up period[10]. Ahmadi et al. demonstrated that the mean time to a decline in eGFR of more than 10 mL/min/1.73 m² from baseline was approximately 5.6 years, even in patients with preoperative CKD stage 3a, suggesting that relatively stable renal function can be maintained despite reduced baseline kidney function[25]. In a study with a longer observation period, Eisenberg et al. reported that approximately 70% of patients experienced renal function deterioration after RC, with a median follow-up duration of 10.5 years[24]. In our cohort, the study population was exclusively male, resulting in a marked sex imbalance. Long-term renal functional outcomes after ONB reconstruction have also been investigated in female-only cohorts. Zahran et al. reported that nearly half of 95 women who were followed for more than 10 years after surgery developed renal function decline[26]. In the present study, renal function gradually declined over the long-term follow-up period, with approximately 30% of patients experiencing decline. These findings align with previous studies that reported mild renal function decline after radical cystectomy and urinary diversion, whereas progression to end-stage renal failure was uncommon. Multivariable analysis found that the type of urinary diversion, including IC and ONB reconstruction, was not an independent predictor of postoperative renal function decline. Therefore, concerns regarding renal outcomes alone may not justify avoiding ONB reconstruction in appropriately selected patients. Instead, careful postoperative management and attention to modifiable risk factors may play an important role in preserving renal function. In our cohort, postoperative hydronephrosis was identified as the only independent predictor of renal function decline, which supports the findings of previous studies. Because hydronephrosis is potentially correctable, timely interventions, such as ureteral stenting or percutaneous nephrostomy, may help prevent further renal deterioration. Thus, early detection and appropriate management of postoperative upper urinary tract obstruction are essential for maintaining long-term renal function after RC. Our findings suggest that ONB reconstruction provides acceptable long-term oncological control, a low incidence of urethral recurrence, and generally preserves renal function. From a clinical perspective, these data support the continued use of ONB as a valid urinary diversion option in appropriately selected patients undergoing RC. This study has several limitations. First, it was retrospective and conducted at a single institution, with a relatively limited sample size, which may limit the generalizability of the findings. Second, patients selected for ONB reconstruction generally represent a favorable subgroup with regard to age, comorbidity, and tumor characteristics. On the other hand, this selection reflects real-world clinical practice, as orthotopic diversion is typically only offered to carefully selected candidates. Therefore, our findings are most applicable to patients who meet the established selection criteria for ONB reconstruction. Nevertheless, the long-term follow-up period and comprehensive assessment of oncological and functional outcomes provide valuable real-world evidence regarding the safety of ONB reconstruction. A strength of this study is that all procedures were performed under the supervision of a single experienced surgeon using consistent selection criteria and surgical techniques. This institutional uniformity may reduce procedural heterogeneity and allow for a more accurate evaluation of long-term functional outcomes, particularly renal function, over an extended follow-up period. Declarations Conflict of interest The authors declare no conflict of interest. Ethical approval The protocol for this research project has been approved by a suitably constituted ethics committee of the institution, and it conforms to the provisions of the Declaration of Helsinki. This study was approved by the Institutional Review Board of Yokosuka Kyosai Hospital (YKH22-55a) Fundings This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Acknowledgements We thank all patients and health care providers who contributed to this study Data availability All data generated or analyzed during this study, which support the findings of this study, are included within this article. Researchers may access analyses not present in the manuscript from the corresponding author upon reasonable request. References Gakis G, Efstathiou J, Lerner SP, Cookson MS, Keegan KA, Guru KA, Shipley WU, Heidenreich A, Schoenberg MP, Sagalowsky AI, Soloway MS, Stenzl A (2013) ICUD-EAU international consultation on bladder cancer 2012: radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder. 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Supplementary Files Table1.jpg Table2.jpg Table3.jpg Table4.jpg Table5.jpg 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. 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Byoin","correspondingAuthor":false,"prefix":"","firstName":"Jurii","middleName":"","lastName":"Karibe","suffix":""},{"id":593054164,"identity":"ca5cd840-6326-42ca-a61b-b33668372f9c","order_by":5,"name":"Yousuke Shibata","email":"","orcid":"","institution":"Yokosuka Kyosai Hospital: Yokosuka Kyosai Byoin","correspondingAuthor":false,"prefix":"","firstName":"Yousuke","middleName":"","lastName":"Shibata","suffix":""},{"id":593054165,"identity":"f7657411-d25b-4168-bb27-04fc714e362d","order_by":6,"name":"Kimitsugu Usui","email":"","orcid":"","institution":"Yokosuka Kyosai Hospital: Yokosuka Kyosai Byoin","correspondingAuthor":false,"prefix":"","firstName":"Kimitsugu","middleName":"","lastName":"Usui","suffix":""},{"id":593054166,"identity":"9d15d385-428a-4ffd-98ea-85ff570051c9","order_by":7,"name":"Hiroki Ito","email":"","orcid":"","institution":"Yokohama City University School of Medicine Graduate School of Medicine: Yokohama Shiritsu Daigaku Igakubu Daigakuin Igaku Kenkyuka","correspondingAuthor":false,"prefix":"","firstName":"Hiroki","middleName":"","lastName":"Ito","suffix":""},{"id":593054167,"identity":"2578ab32-5659-418e-b7ed-7c6d5a866ddf","order_by":8,"name":"Kazuki Kobayashi","email":"","orcid":"","institution":"Yokosuka Kyosai Hospital: Yokosuka Kyosai Byoin","correspondingAuthor":false,"prefix":"","firstName":"Kazuki","middleName":"","lastName":"Kobayashi","suffix":""}],"badges":[],"createdAt":"2026-02-04 03:07:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8781132/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8781132/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103177481,"identity":"13359182-f4c2-4300-8eaa-86dbd1d3f828","added_by":"auto","created_at":"2026-02-22 16:51:30","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":202151,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in median eGFR after radical cystectomy with orthotopic neobladder\u003c/p\u003e\n\u003cp\u003eacross the postoperative period\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8781132/v1/668b6d9aa54e15f4c04c8ece.jpg"},{"id":103177482,"identity":"69d97ee3-e33b-438a-acf6-5146788a9310","added_by":"auto","created_at":"2026-02-22 16:51:30","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":183951,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves for recurrence-free survival stratified by pathological T stage. The log-rank test demonstrated a significant difference between groups (\u003cem\u003eP\u003c/em\u003e = 0.002).\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8781132/v1/babad10863a6f59e6aff27c8.jpg"},{"id":103509036,"identity":"378797c7-e37d-48f0-880a-3340d711a63a","added_by":"auto","created_at":"2026-02-26 13:56:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":793970,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8781132/v1/98d266e1-b40f-4642-846e-d979d3336f21.pdf"},{"id":103504606,"identity":"9ee4df43-98ba-4798-9ff8-91b56e5e7294","added_by":"auto","created_at":"2026-02-26 13:20:44","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":421630,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8781132/v1/d1b06108e7d0f79635ee8870.jpg"},{"id":103177485,"identity":"31b5cda0-0a51-4d4e-ad8d-dd007bbbd160","added_by":"auto","created_at":"2026-02-22 16:51:30","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":326296,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8781132/v1/0c38b0b8da38496a4dde7444.jpg"},{"id":103177483,"identity":"a2e93ef0-ea9d-426f-8084-715af669bde8","added_by":"auto","created_at":"2026-02-22 16:51:30","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":495167,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8781132/v1/6feaac1fa758e557eb839b73.jpg"},{"id":103177487,"identity":"744c8a19-96ea-4b1b-b485-38671ca1dde7","added_by":"auto","created_at":"2026-02-22 16:51:30","extension":"jpg","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":596150,"visible":true,"origin":"","legend":"","description":"","filename":"Table4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8781132/v1/8f4db0f2be672f9836a357a0.jpg"},{"id":103504603,"identity":"1a7ca09e-ea54-400c-a859-b363275d398c","added_by":"auto","created_at":"2026-02-26 13:20:43","extension":"jpg","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":487756,"visible":true,"origin":"","legend":"","description":"","filename":"Table5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8781132/v1/bfbead8a6d9b98d0408bf691.jpg"}],"financialInterests":"","formattedTitle":"Long-term Functional and Oncological Outcomes after Radical Cystectomy with Orthotopic Neobladder: A single Institution Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRadical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for muscle-invasive bladder cancer and selected high-risk non-muscle-invasive disease patients[1]. After RC, urinary diversion is required, with ileal conduit (IC) and orthotopic neobladder (ONB) being the most commonly utilized diversion types. IC is the standard approach because of its safety and oncological effectiveness[2].\u003c/p\u003e \u003cp\u003eONB reconstruction has gained increasing acceptance in selected patients, as it offers potential improvements in body image and quality of life while maintaining acceptable oncological outcomes[3]. However, concerns remain regarding the long-term oncological safety and functional outcomes. In particular, whether orthotopic diversion compromises cancer control, increases the risk of urethral recurrence, or leads to progressive renal dysfunction remain to be elucidated, especially in real-world clinical settings with extended follow-up[4].\u003c/p\u003e \u003cp\u003ePrevious studies have reported that long-term survival after RC is primarily determined by tumor-related factors rather than the type of urinary diversion and that ONB reconstruction achieves oncological outcomes comparable to incontinent diversion in selected patients[5,6]. In addition to oncological control, preservation of renal function is an important consideration after ONB reconstruction. Renal function is preserved in most patients; however, late deterioration has been observed, most commonly in association with postoperative hydronephrosis or upper urinary tract obstruction, independent of urinary diversion type[7\u0026ndash;10]. Long-term single-institution data evaluating oncological control, urethral recurrence, and renal function simultaneously remain limited.\u003c/p\u003e \u003cp\u003eThe aim of the present study was to evaluate the long-term oncological and functional outcomes of patients undergoing RC with ONB reconstruction at a single institution. Specifically, we focused on recurrence patterns, urethral recurrence, and longitudinal changes in renal function to assess the overall safety and clinical validity of ONB reconstruction in routine practice.\u003c/p\u003e"},{"header":"Materials \u0026 Methods","content":"\u003cp\u003ePatient Selection\u003c/p\u003e \u003cp\u003e We retrospectively reviewed the medical records of patients who underwent RC with ONB reconstruction for bladder cancer at Yokosuka Kyosai Hospital between June 2009 and August 2024. The criteria for selecting a urinary diversion at the time of RC were as follows. ONB reconstruction was selected for patients younger than 75 years who had no tumor involvement of the bladder neck and were expected to be capable of postoperative self-catheterization. Urethral biopsy prior to ONB creation was performed at the surgeon\u0026rsquo;s discretion, and ONB reconstruction was avoided in tumor-positive cases in urethral biopsy. IC diversion was selected for patients who were able to manage stoma care and pouch replacement independently regardless of tumor location. Cutaneous ureterostomy was selected for patients in whom bowel use was contraindicated due to factors such as severe adhesions, as well as for elderly patients or those with significant comorbidities and relatively limited tolerance for major surgery.\u003c/p\u003e \u003cp\u003eA total of 84 consecutive patients were included in this study. All procedures were performed under the supervision of a single expert surgeon. Patients who had previously undergone urinary diversion and those with insufficient follow-up data were excluded. The study protocol was approved by the Institutional Review Board, and the requirement for informed consent was waived owing to the retrospective nature of the study (approval number: YKH22-55a).\u003c/p\u003e \u003cp\u003eData Collection\u003c/p\u003e \u003cp\u003eBaseline characteristics, including sex, age, smoking history, and receipt of neoadjuvant chemotherapy (NAC), were recorded. Pathological findings were reviewed, including tumor stage, nodal status, presence of variant histology, and urethral and ureteral margin status. Postoperative adjuvant chemotherapy and recurrence patterns (local or distant) were documented.\u003c/p\u003e \u003cp\u003eThe primary oncological endpoint was PFS, defined as the time from surgery to disease recurrence. Recurrence was confirmed by radiographic or pathological evidence.\u003c/p\u003e \u003cp\u003eEstimated glomerular filtration rate (eGFR) was calculated using the Japanese Society of Nephrology formula at baseline and every year after surgery. Renal function decline was defined as a reduction of \u0026ge;\u0026thinsp;25% compared with preoperative eGFR one year after surgery. All postoperative complications (early [\u0026le; 30 days] and late [\u0026gt;\u0026thinsp;30 days]) were graded using the Clavien\u0026ndash;Dindo classification system, and the details were recorded.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eSurvival curves were generated using the Kaplan\u0026ndash;Meier method. Differences between groups were compared with the log-rank test. Univariate and multivariate analyses for PFS were performed using the Cox proportional hazards model, with results expressed as hazard ratios and 95% confidence intervals. Variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in univariate analysis were entered into the multivariate model.\u003c/p\u003e \u003cp\u003eFor renal function analysis, potential predictors, including age, preoperative eGFR, hydronephrosis, and urinary tract infection, were analyzed using univariate logistic regression. Variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were subsequently assessed by multivariate logistic regression. Significance was defined as a p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Japan), a graphical user interface for R[11].\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 84 male patients who underwent RC with ONB reconstruction were included in the analysis. The median age was 68\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2 years. Forty-one patients (48.8%) had a history of smoking. NAC was administered in 36 patients (42.9%). Pathological examination revealed\u0026thinsp;\u0026le;\u0026thinsp;pT1 in 56, pT2 in 10, pT3 in 17, and pT4 in one patient. Nodal metastasis was detected in nine patients. Variant histology was present in nine cases. The bladder tumor locations were distributed as follows: posterior wall (n\u0026thinsp;=\u0026thinsp;14), anterior wall (n\u0026thinsp;=\u0026thinsp;5), trigone (n\u0026thinsp;=\u0026thinsp;22), dome (n\u0026thinsp;=\u0026thinsp;3), lateral wall (n\u0026thinsp;=\u0026thinsp;10), ureteric orifice (n\u0026thinsp;=\u0026thinsp;8), and overlapping lesion (n\u0026thinsp;=\u0026thinsp;22) (Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eShort-term (within 30 days) complications occurred in 47.6% (40/84) of patients, consisting of Clavien Grade \u0026le; II in 32 patients and Grade III in eight. Long-term (beyond 30 days) complications occurred in 27.4% (23/84) of patients, consisting of Clavien Grade \u0026le; II in nine cases and Grade III in 14 (Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eThe median follow-up was 79 months (range, 4\u0026ndash;179). During follow-up, 21 patients experienced recurrence, including four local recurrences and 17 distant recurrences (lymph nodes in 12, lung in six, and liver in three). The median time to recurrence was 18.4 months (range, 2\u0026ndash;87). The 5- and 10-year recurrence-free survival (RFS) rates were 76% and 72%, respectively. The 5- and 10-year cancer-specific survival (CSS) rates were 92% and 83%, respectively. Urethral recurrence was not observed in any patient, including those that did not undergo preoperative urethral biopsy (n\u0026thinsp;=\u0026thinsp;63). The cutoff values were set at 3 for NLR, 4 g/dL for albumin, and 12 g/dL for hemoglobin based on previous studies[12\u0026ndash;14]. In univariate Cox analysis, pathological T category (HR 3.635 95% CI 1.501\u0026ndash;8.805, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), pathological N category (HR 3.61, 95% CI 1.3\u0026ndash;9.9, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0127), and receipt of adjuvant chemotherapy (HR 3.121, 95% CI 1.2\u0026ndash;8.08, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.019) were significantly associated with PFS. In multivariate analysis, only pathological T category remained significant (HR 2.976, 95% CI 1.18\u0026ndash;7.51, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021). Median RFS was not reached in both groups; however, patients with pT\u0026thinsp;\u0026ge;\u0026thinsp;2 disease showed significantly worse RFS (log-rank \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMedian eGFR declined from 66.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.6 mL/min/1.73 m\u0026sup2; preoperatively to 52.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.4 at 12 months, 54.4\u0026thinsp;\u0026plusmn;\u0026thinsp;15.5 at 36 months, 54.2\u0026thinsp;\u0026plusmn;\u0026thinsp;17 at 60 months, and 49.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4 at 120 months postoperatively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). When decline was defined as a\u0026thinsp;\u0026ge;\u0026thinsp;25% decrease from baseline one year after surgery, 22 of 78 patients (28.2%) showed decline. In univariate analyses, the presence of postoperative hydronephrosis was the only significant predictor of renal function decline (Table\u0026nbsp;3).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, RC with ONB reconstruction was associated with favorable long-term oncological and functional outcomes, without apparent increases in recurrence, urethral recurrence, or severe renal deterioration. These findings support the oncological safety and clinical validity of ONB reconstruction in appropriately selected patients.\u003c/p\u003e \u003cp\u003eOur oncological outcomes are comparable to those reported in contemporary large series. In a critical review of RC with ONB reconstruction, Stenzl et al. reported overall 5- and 10-year RFS rates of 62\u0026ndash;68% and 50\u0026ndash;66%, respectively, in patients with organ-confined disease[15]. Similarly, in a population-based analysis using the SEER database, Su et al. reported 5-year CSS probabilities of 55% for IC diversion and 72.9% for ONB diversion[5]. Cheng et al. reported favorable mid-term outcomes after robotic intracorporeal Studer neobladder reconstruction, with a 60-month cumulative RFS rate of 87.4%[16]. Our cohort demonstrated 5- and 10-year RFS rates of 76% and 72%, and 5- and 10-year CSS rates of 92% and 83%, respectively. Although differences in patient selection, baseline characteristics, and surgical approaches across studies must be considered, these findings suggest that the long-term oncological outcomes of our real-world ONB reconstruction population were similar to those reported in previous large-scale or contemporary series. This may partly reflect orthotopic diversion being typically offered to carefully selected patients with favorable clinical profiles.\u003c/p\u003e \u003cp\u003eSeveral landmark studies, including the cohort reported by Stein et al., demonstrated that long-term survival after RC is primarily determined by tumor-related factors and that the type of urinary diversion does not independently compromise cancer control[17]. More recent population-based and multicenter studies have similarly reported that ONB reconstruction provides RFS and overall survival outcomes comparable to those of IC diversion when appropriate selection criteria are applied. In the present cohort, the overall recurrence rate and recurrence patterns were within the range reported in contemporary literature[5,15,16,18,19]. These real-world data with long-term follow-up further support the hypothesis that orthotopic diversion itself does not adversely affect oncological outcomes and should not be avoided solely because of concerns regarding cancer control.\u003c/p\u003e \u003cp\u003eWe explored the potential role of the NLR as a predictor of recurrence. In contrast to some previous reports[20,21], NLR was not significantly associated with oncological outcomes in our cohort and did not provide additional prognostic value, suggesting it should be interpreted cautiously in clinical decision-making. In contrast, Kawahara et al. reported that elevated preoperative NLR was an independent prognostic marker for cancer-specific mortality in a broader RC population, irrespective of diversion type[21]. This discrepancy may be attributable to differences in cohort composition, as our study focused exclusively on ONB reconstruction patients, a selected group with generally favorable baseline characteristics. Moreover, the limited sample size and low event rate in ONB reconstruction cohorts may have reduced the power to detect modest prognostic effects. Thus, the prognostic utility of NLR may vary depending on patient background and urinary diversion strategy.\u003c/p\u003e \u003cp\u003eUrethral recurrence represents a specific oncological concern after RC, particularly in patients undergoing orthotopic diversion. A previous systematic review reported urethral recurrence rates ranging from approximately 1% to 14%, and identified various risk factors including multifocal disease, carcinoma in situ, bladder neck involvement, and prostatic urethral invasion[22]. Notably, in our cohort, no urethral recurrence was observed, including in patients who did not undergo routine preoperative urethral biopsy. Although careful patient selection remains essential, these findings suggest that urethral preservation without routine biopsy is oncologically acceptable in selected patients in real-world practice.\u003c/p\u003e \u003cp\u003eLong-term renal function is a major concern following RC. Previous studies reported that postoperative renal deterioration is influenced predominantly by patient-related and obstructive factors rather than by the type of urinary diversion[9,23]. Similarly, a large retrospective cohort study of 670 patients reported that progression of chronic kidney disease (CKD) after RC was associated with preoperative hydronephrosis, adjuvant chemotherapy, comorbidity burden, and baseline renal function, whereas the type of urinary diversion was not identified as an independent risk factor[8]. Eisenberg et al., in a cohort with a median follow-up of 10 years, reported that the rate of renal function deterioration was similar between patients undergoing ONB reconstruction and those receiving IC diversion[24]. Furthermore, a propensity score-matched analysis comparing three urinary diversion techniques (ONB, IC, and cutaneous ureterostomy) demonstrated no significant difference in long-term eGFR decline between a neobladder group and those that received other diversion types[10]. These results support the hypothesis that postoperative renal outcomes are multifactorial and largely determined by preexisting conditions and perioperative factors. In particular, the presence of postoperative hydronephrosis was reported as a significant predictor of renal function decline after ONB reconstruction\u003csup\u003e8\u003c/sup\u003e. This finding underscores the importance of surgical technique and careful postoperative surveillance to prevent upper urinary tract obstruction.\u003c/p\u003e \u003cp\u003eSeveral studies have reported longitudinal decline in renal function following RC. Hatakeyama et al. reported an approximate 15% decline in renal function over a five-year follow-up period[10]. Ahmadi et al. demonstrated that the mean time to a decline in eGFR of more than 10 mL/min/1.73 m\u0026sup2; from baseline was approximately 5.6 years, even in patients with preoperative CKD stage 3a, suggesting that relatively stable renal function can be maintained despite reduced baseline kidney function[25]. In a study with a longer observation period, Eisenberg et al. reported that approximately 70% of patients experienced renal function deterioration after RC, with a median follow-up duration of 10.5 years[24].\u003c/p\u003e \u003cp\u003eIn our cohort, the study population was exclusively male, resulting in a marked sex imbalance. Long-term renal functional outcomes after ONB reconstruction have also been investigated in female-only cohorts. Zahran et al. reported that nearly half of 95 women who were followed for more than 10 years after surgery developed renal function decline[26].\u003c/p\u003e \u003cp\u003eIn the present study, renal function gradually declined over the long-term follow-up period, with approximately 30% of patients experiencing decline. These findings align with previous studies that reported mild renal function decline after radical cystectomy and urinary diversion, whereas progression to end-stage renal failure was uncommon. Multivariable analysis found that the type of urinary diversion, including IC and ONB reconstruction, was not an independent predictor of postoperative renal function decline. Therefore, concerns regarding renal outcomes alone may not justify avoiding ONB reconstruction in appropriately selected patients. Instead, careful postoperative management and attention to modifiable risk factors may play an important role in preserving renal function. In our cohort, postoperative hydronephrosis was identified as the only independent predictor of renal function decline, which supports the findings of previous studies. Because hydronephrosis is potentially correctable, timely interventions, such as ureteral stenting or percutaneous nephrostomy, may help prevent further renal deterioration. Thus, early detection and appropriate management of postoperative upper urinary tract obstruction are essential for maintaining long-term renal function after RC.\u003c/p\u003e \u003cp\u003eOur findings suggest that ONB reconstruction provides acceptable long-term oncological control, a low incidence of urethral recurrence, and generally preserves renal function. From a clinical perspective, these data support the continued use of ONB as a valid urinary diversion option in appropriately selected patients undergoing RC.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, it was retrospective and conducted at a single institution, with a relatively limited sample size, which may limit the generalizability of the findings. Second, patients selected for ONB reconstruction generally represent a favorable subgroup with regard to age, comorbidity, and tumor characteristics. On the other hand, this selection reflects real-world clinical practice, as orthotopic diversion is typically only offered to carefully selected candidates. Therefore, our findings are most applicable to patients who meet the established selection criteria for ONB reconstruction. Nevertheless, the long-term follow-up period and comprehensive assessment of oncological and functional outcomes provide valuable real-world evidence regarding the safety of ONB reconstruction. A strength of this study is that all procedures were performed under the supervision of a single experienced surgeon using consistent selection criteria and surgical techniques. This institutional uniformity may reduce procedural heterogeneity and allow for a more accurate evaluation of long-term functional outcomes, particularly renal function, over an extended follow-up period.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eConflict of interest\u003c/strong\u003e \u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical approval\u003c/strong\u003e \u003cp\u003eThe protocol for this research project has been approved by a suitably constituted ethics committee of the institution, and it conforms to the provisions of the Declaration of Helsinki. This study was approved by the Institutional Review Board of Yokosuka Kyosai Hospital (YKH22-55a)\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFundings\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eWe thank all patients and health care providers who contributed to this study\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eAll data generated or analyzed during this study, which support the findings of this study, are included within this article. Researchers may access analyses not present in the manuscript from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e Gakis G, Efstathiou J, Lerner SP, Cookson MS, Keegan KA, Guru KA, Shipley WU, Heidenreich A, Schoenberg MP, Sagalowsky AI, Soloway MS, Stenzl A (2013) ICUD-EAU international consultation on bladder cancer 2012: radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder. Eur Urol 63:45\u0026ndash;57. https://doi.org/10.1016/j.eururo.2012.08.009\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Feng D, Liu S, Lu Y, Wei W, Han P (2020) Clinical efficacy and safety of enhanced recovery after surgery for patients treated with radical cystectomy and ileal urinary diversion: a systematic review and meta-analysis of randomized controlled trials. 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PLoS One 11:e0149544. https://doi.org/10.1371/journal.pone.0149544\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Kanda Y (2013) Investigation of the freely available easy-to-use software \u0026ldquo;EZR\u0026rdquo; for medical statistics. Bone Marrow Transplant 48:452\u0026ndash;458. https://doi.org/10.1038/bmt.2012.244\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Hermanns T, Bhindi B, Wei Y, Yu J, Noon AP, Richard PO, Bhatt JR, Almatar A, Jewett MAS, Fleshner NE, Zlotta AR, Templeton AJ, Kulkarni GS (2014) Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder. 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World J Urol 34:829\u0026ndash;834. https://doi.org/10.1007/s00345-015-1691-4\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Stenzl A, Cowan NC, De Santis M, Kuczyk MA, Merseburger AS, Ribal MJ, Sherif A, Witjes JA; European Association of Urology (EAU) (2010) Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines. Int Braz J Urol 36:512\u0026ndash;521. https://doi:10.1016/j.eururo.2011.03.023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Cheng Q, Lu Y, Jiang B, Ai Q, Gao F, Zhao X, Tang J, Feng Y, Gao W, Li H (2025) Oncological and functional outcomes and complications of robotic intracorporeal Studer orthotopic neobladder: A single-center retrospective study. 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BMC Cancer 16:185. https://doi.org/10.1186/s12885-016-2219-z\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Laukhtina E, Mori K, D\u0026rsquo;Andrea D, Moschini M, Abufaraj M, Soria F, Mari A, Krajewski W, Albisinni S, Teoh JYC, Quhal F, Sari Motlagh R, Mostafaei H, Katayama S, Grossmann NC, Rajwa P, Enikeev D, Zimmermann K, Fajkovic H, Glybochko P, Shariat SF, Pradere B; European Association of Urology\u0026ndash;Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) (2021) Incidence, risk factors and outcomes of urethral recurrence after radical cystectomy: a systematic review and meta-analysis. Urol Oncol 39:806\u0026ndash;815. https://doi.org/10.1016/j.urolonc.2021.07.014\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Jin XD, Roethlisberger S, Burkhard FC, Birkhaeuser F, Thoeny HC, Studer UE (2010) Long-term renal function after urinary diversion by ileal conduit or orthotopic ileal bladder substitution. Eur Urol 61(3):491-7. https://doi:10.1016/j.eururo.2011.09.004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Eisenberg MS, Thompson RH, Frank I, Kim SP, Cotter KJ, Tollefson MK, Kaushik D, Thapa P, Tarrell R, Boorjian SA (2013) Long-term renal function outcomes after radical cystectomy. J Urol 190:2059\u0026ndash;2064. https://doi.org/10.1016/j.juro.2013.09.011\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Ahmadi H, Reddy S, Nguyen C, Douglawi A, Ladi-Seyedian S, Roberts S, Ghoreifi A, Ghodoussipour S, Bhanvadia SK, Djaladat H, Schuckman A, Daneshmand S (2022) Long-term renal function in patients with chronic kidney disease following radical cystectomy and orthotopic neobladder. BJU Int. 130(2):200\u0026ndash;207. https://doi:10.1111/bju.15685.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Zahran MH, Harraz AM, Baset MA, El-Baz R, Shaaban AA, Ali-El-Dein B (2023) Voiding and renal function 10 years after radical cystectomy and orthotopic neobladder in women. BJU Int. 132(3):291\u0026ndash;297.\u003c/span\u003e \u003cspan\u003ehttps://doi:10.1111/bju.16011\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 5 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":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":"radical cystectomy, orthotopic neobladder, urethral recurrence, urethral biopsy, renal function","lastPublishedDoi":"10.21203/rs.3.rs-8781132/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8781132/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRadical cystectomy (RC) with orthotopic neobladder (ONB) reconstruction provides oncological control and quality-of-life benefits for selected patients with bladder cancer. However, prognostic factors for recurrence remain to be elucidated. Herein, we evaluated oncological outcomes after ONB reconstruction.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We retrospectively reviewed 84 patients who underwent RC with ONB reconstruction at our institution between June 2009 and August 2024. We analyzed clinicopathological characteristics, perioperative variables, and postoperative outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAll patients were male, the median age was 68\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2 years, and the median follow-up was 79 months (range, 4\u0026ndash;179). The 5- and 10-year recurrence-free survival (RFS) rates were 76% and 72%, and the 5- and 10-year cancer-specific survival rates were 92% and 83%, respectively. In univariate analysis, postoperative nodal status, adjuvant chemotherapy, and postoperative T status were significantly associated with RFS. Multivariate analysis identified postoperative T status as the only independent predictor (HR 2.976, 95% CI 1.179\u0026ndash;7.5132, p\u0026thinsp;=\u0026thinsp;0.021).\u003c/p\u003e","manuscriptTitle":"Long-term Functional and Oncological Outcomes after Radical Cystectomy with Orthotopic Neobladder: A single Institution Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-22 16:51:25","doi":"10.21203/rs.3.rs-8781132/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":"6cf47f5f-fe2e-4d85-b228-7a56f09ced8d","owner":[],"postedDate":"February 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-24T04:05:46+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-22 16:51:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8781132","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8781132","identity":"rs-8781132","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}