We present a summary of the 2025 update for the European Association of Urology (EAU) guidelines for upper urinary tract urothelial carcinoma (UTUC). The aim is to provide practical recommendations on the clinical management of UTUC with a focus on diagnosis, treatment, and follow-up.

For the 2025 guidelines on UTUC, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences.

Key recommendations emphasise the importance of thorough diagnosis, treatment, and follow-up for patients with UTUC. The guidelines stress the importance of appropriate treatment taking into account patient values and preferences. Key updates in the 2025 UTUC guidelines include: significant changes to the recommendations for UTUC diagnosis; complete revision of the sections addressing risk stratification, ureteroscopy, and the surgical approach for radical nephroureterectomy; addition of four new recommendations, two related to kidney-sparing management of localised low-risk UTUC and a further two related to management of high-risk nonmetastatic UTUC; a review and adaptation of recommendation for UTUC follow-up; and addition of a new section addressing quality indicators for UTUC management.

This overview of the 2025 EAU guidelines on UTUC offers valuable insights into risk factors, diagnosis, classification, treatment, and follow-up for UTUC. The guidelines contain information on the management of individual patients according to the current best evidence and are designed for effective integration in clinical practice.

To evaluate the effects of adjuvant chemotherapy (AC) and adjuvant immunotherapy (AI) on the prognosis of patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). A systematic review and meta-analysis was conducted using studies identified from PubMed, Cochrane Library, Embase, CENTRAL, and ClinicalTrials.gov up to September 2024. We performed pair-wise and network meta-analyses to evaluate survival outcomes, focusing on overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), recurrence-free survival, and metastasis-free survival. A total of 43 studies involving 13,132 patients were included. Pair-wise meta-analysis showed that AC significantly improved OS (HR 0.74, 95% CI 0.63-0.86, P = 0.0001), CSS (HR 0.74, 95% CI 0.60-0.90, P < 0.00001), and DFS (HR 0.61, 95% CI 0.51-0.75, P < 0.00001). A pooled analysis of three RCTs with 384 UTUC patients showed that AI did not significantly improve DFS (HR 1.19, 95% CI 0.87-1.64, P = 0.28) or OS (HR 1.28, 95% CI 0.81-2.03). Network meta-analysis suggested that combining AC with AI could offer better DFS than AC alone, with AC outperforming AI. Ranking analysis indicated that MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) was the most effective for OS and CSS improvement, followed by GC (gemcitabine and cisplatin). AC improves the prognosis of UTUC patients, whereas the results with AI are less promising. AC shows better outcomes than AI after RNU. Preliminary evidence suggests that combining AC with AI may enhance DFS, but further research is needed to confirm its effectiveness.

To evaluate the preoperative risk factors for early intravesical recurrence after radical nephroureterectomy (RNU) in patients with upper urinary tract carcinoma (UTUC) according to the history of non-muscle invasive bladder cancer (NMIBC).

We retrospectively evaluated patients who underwent RNU for UTUC between 2012 and 2022 at 14 hospitals. Early recurrence was defined as intravesical pathologically confirmed recurrence within 1 year after RNU. Patients who received single-dose immediate intravesical instillation (IVI) as prevention for intravesical recurrence were excluded. Using preoperative factors, we examined the risk factors for early intravesical recurrences in patients with and without a history of NMIBC. Death from any cause within 1 year after RNU was regarded as a competitive risk.

We included 504 UTUC patients who were treated with RNU. Among these patients, 126 (25.0%) had a history of NMIBC, whereas 378 (75%) did not. According to multivariate analysis, the presence of macrohematuria, positive cytology in self-voided urine, and performing diagnostic ureteroscopy prior to RNU were risk factors in patients without a history of NMIBC. On the other hand, an NMIBC diagnosis within 1 year prior to RNU and an extravesical approach for bladder cuff management were risk factors in RNU-treated patients with a history of NMIBC.

Early intravesical recurrence risk factors differ between UTUC patients with and without a history of NMIBC. Different stratification may be needed to predict intravesical recurrence risk in these two types of UTUC patients.

Intravesical instillation of chemotherapy (IIC) after radical surgery for upper urinary tract urothelial carcinoma (UTUC) reduces the risk of intravesical recurrence (IVR). However, compliance is low because of possible extravesical leakage after bladder cuff excision. The aim of this study was to evaluate the efficacy of preoperative IIC in reducing the risk of IVR.

In this prospective, single-arm, multi-institutional, phase 2 clinical trial, 190 chemonaïve patients with primary UTUC without prior or concurrent bladder cancer received a single intravesical instillation of mitomycin C for 1-2 hr within 3 h before surgery. The primary endpoint was the 2-yr histologically confirmed IVR rate, with a target reduction of >40% (from 33.2% according to literature data to <20%). A historical cohort of 247 patients with UTUC who did not receive perioperative IIC served as the reference. Secondary endpoints included compliance, toxicity, and IVR-free survival, which was analyzed via multivariable Cox regression and stratified by previous diagnostic ureteroscopy (d-URS).

The 2-yr IVR rate was 24% (95% confidence interval [CI] 18-31%) on intention-to-treat analysis and 23% (95% CI 13-32%) on per-protocol analysis. Multivariable analysis revealed that d-URS was associated with higher IVR risk. In the REBACARE cohort, patients without d-URS had threefold lower IVR risk (hazard ratio 0.33, 95% CI 0.12-0.87) in comparison to the reference cohort. Compliance with preoperative instillation was 96% and no grade >2 toxicity occurred.

Preoperative IIC with mitomycin C was feasible and well tolerated and significantly reduced IVR risk for patients without d-URS. These findings suggest that preoperative IIC is a viable strategy for this subset of UTUC patients and that d-URS should be performed judiciously.

Although the preventive effect against intravesical recurrence (IVR) has been established for single instillation of chemotherapy during or after radical surgery of upper urinary tract urothelial carcinoma (UTUC), there has been no research on the long-term outcome. This study aims to investigate the IVR and long-term survival outcome of a single intraoperative instillation of pirarubicin during radical nephroureterectomy (RNU).

In this prospective, multicenter, randomized trial, 97 patients undergoing RNU between August 2012 and January 2019 were randomly assigned either to receive a single intraoperative pirarubicin instillation or to serve as the controls.

A total of 80 patients were analyzed, including 42 in the pirarubicin group and 38 in the control group. The median follow-up period was 58.5 months and 62 months in the pirarubicin and the control groups, respectively. In patients who did not experience IVR, the median follow-up period was 59 months and 61 months in the pirarubicin and the control groups, respectively. There was no significant difference in OS between the two groups, although the IVR rate was significantly lower in pirarubicin group (p = 0.044). Multivariable analyses revealed that the pirarubicin instillation was the only independent factor for IVR.

The present trial demonstrated that a single intraoperative instillation of pirarubicin resulted in a significant and long-term reduction of IVR, although there was no significant difference in OS.

Intravesical recurrence of upper tract urothelial carcinoma after radical nephroureterectomy occurs in 22% to 47%. Intravesical chemotherapy is still underused due to concerns about its efficacy and safety. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of intravesical chemotherapy regimens in reducing the risk of intravesical recurrence following radical nephroureterectomy.

A literature search was conducted using PubMed/Medline, Embase, and Web of Science databases to identify reports published until March 2024. The PRISMA guidelines were followed to identify eligible studies. The outcomes measured were intravesical recurrence rates and complications in patients treated with different intravesical instillation chemotherapy and timing after radical nephroureterectomy. Sub-analyses were performed on randomized controlled trials and studies involving patients with no history of bladder cancer.

Eighteen studies met our inclusion criteria, and data from 2,483 patients were reviewed. Intravesical chemotherapy significantly reduced the risk of intravesical recurrence at 12 months (OR = 0.46; 95% CI: 0.33-0.65; P < 0.001;) and at 24 months (OR = 0.41, 95% CI: 0.28-0.61; P < 0.001). Notably, no association was found when confronting intra and postoperative instillations (OR = 0.66; 95% CI: 0.34-1.28; P = 0.2), nor single vs. multiple instillation (OR = 1.37; 95% CI: 0.75-2.50; P = 0.3). The pooled rate for minor and major complications was 9% and 0.9%, respectively.

This study demonstrates that intravesical chemotherapy significantly reduces intravesical recurrence rates after radical nephroureterectomy at 12 and 24 months. Additionally, it underscores the favorable safety profile of intravesical chemotherapy, with a low incidence of major complications. The ideal instillation scheme and chemotherapy agent should be further defined.

Ailanthone (AIL), a medicinal component with antitumor properties, was distilled from Ailanthus altissima. The aim of this work was to probe the cancer-fighting effect of AIL on bladder cancer (BC) cells and the molecular basis of this effect.

We developed a subcutaneous BC mouse model and then administered AIL treatment. The effects of AIL on tumor tissue integrity and apoptosis were analyzed using hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining methods. Furthermore, we investigated the effect of AIL on the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway and associated proteins through quantitative reverse transcription polymerase chain reaction and Western blot analysis. Various concentrations of AIL were applied to BC cells, and its effects on cell survival, motility, and apoptosis were detected through cell counting kit-8 assay, Transwell assay, and flow cytometry. In addition, we examined the influence of AIL on apoptosis-related proteins and epithelialmesenchymal transition (EMT)-related proteins in BC cells through Western blot analysis.

AIL significantly suppressed the growth and migration of 5637 and T24 cells while promoting apoptosis (P < 0.05, P < 0.01, and P < 0.001). In addition, AIL increased the levels of cell death-associated proteins (P < 0.05, P < 0.01, and P < 0.001) and reversed EMT in BC cells. In vivo, AIL treatment reduced tumor growth and lowered the transcriptional levels of interleukin (IL)-6, IL-10, and IL-23, which are activation factors in the JAK/STAT3 signaling pathway. It also decreased the phosphorylation levels of JAK1, JAK2, and STAT3 in tumor tissues (P < 0.05 and P < 0.01).

AIL exhibits multiple anticancer effects, such as BC cell growth suppression, apoptosis enhancement, reversion of EMT reversion, tumor growth, and JAK/STAT3 pathway activation suppression.

The purpose of this review is to summarize the most recent evidence on surgical management, strategies to reduce tumor recurrence, and surveillance regimens in patients diagnosed with upper tract urothelial carcinoma (UTUC) and elected for radical treatment.

Minimally invasive surgery is gaining momentum in the surgical management of UTUC. Chemoprophylaxis is still the gold standard to reduce intravesical recurrence after radical nephroureterectomy (RNU). Novel surveillance strategies have been proposed to adapt follow-up regimens to patients' characteristics.

Minimally invasive surgery has been associated with comparable oncological outcomes to the open approach while improving postoperative morbidity. In these cases, bladder cuff excision (BCE) is mostly performed by an extravesical approach, that demonstrates a noninferiority compared to the intravesical one in terms of oncological outcomes. Although lymphadenectomy is recommended in patients with high-risk tumors, its benefits are still unclear. Currently, there is a lack of recent prospective trials on chemoprophylaxis to reduce intravesical recurrence post RNU, making single-dose postoperative chemotherapy instillation the standard treatment. Although novel risk stratification models were released by international urological guidelines, their validity is mainly nonevidence-based. Risk-adapted follow-up strategies incorporating cystoscopy and cross-sectional imaging accounting for individual patient factors should be implemented.

The purpose of this study was to propose an update of the French guidelines from the national committee ccAFU on upper tract urothelial carcinomas (UTUC).

A systematic Medline search for epidemiology, risk factors, diagnosis, prognosis, treatment options and follow-up of UTUC was performed between 2022 and 2024 to evaluate available references and their levels of evidence.

UTUC is a rare malignancy with specific risk factors, including exposure to aristolochic acid and Lynch syndrome. Its diagnosis is based on the use of computed tomography urography and ureterorenoscopy with biopsies. A prognostic classification has been proposed to discriminate low- and high-risk lesions mainly on the basis of tumour grade (low/high) and imaging aspects (non-invasive/invasive). Tumour size (<2/≥2cm), focality (uni-/multifocal), and hydronephrosis (absent/present) are more relative risk factors. The standard of care for low-risk patients is currently conservative treatment involving ureterorenoscopy laser ablation, whereas radical nephroureterectomy (RNU) is advised for those with high-risk disease. Adjuvant treatments after RNU include intravesical instillation of chemotherapy to decrease the risk of bladder recurrence and delivery of platinum-based chemotherapy in pT2-T4 and/or pN+ patients. First-line treatment for metastatic UTUC is based on the combination of enfortumab vedotin plus pembrolizumab. For unfit patients, platinum-based chemotherapy plus nivolumab followed by maintenance nivolumab or platinum-based chemotherapy followed by maintenance avelumab in those with at least stable disease can be proposed. The surveillance regimen and schedule depend on the disease stage.

These updated guidelines will contribute to improving the management of patients diagnosed with UTUC.

We sought to determine whether bladder cuff excision and its technique influence outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).

A multicenter, international, retrospective analysis using the ROBotic surgery for Upper tract Urothelial cancer Study (ROBUUST) 2.0 registry identified 1,718 patients undergoing RNU for UTUC between 2015 and 2023 at 17 centers across the United States, Europe, and Asia. Data was gathered on (1) whether bladder cuff excision was performed and (2) what technique was used, including formal excision or other techniques (pluck technique, stripping/intussusception technique) and outcomes. Multivariate and survival analyses were performed to compare the groups.

Most patients (90%, 1,540/1,718) underwent formal bladder cuff excision in accordance with EAU and AUA guidelines. Only 4% (68/1,718) underwent resection using other techniques, and 6% (110/1,718) did not have a bladder cuff excised. Median follow up for the cohort was 24 months (IQR 9-44). When comparing formal bladder cuff excision to other excision techniques, there were no differences in oncologic or survival outcomes including bladder recurrence-free survival (BRFS), recurrence-free survival (RFS), metastasis-free survival (MFS), overall survival (OS), or cancer-specific survival (CSS). However, excision of any kind conferred a decreased risk of bladder-specific recurrence compared to no excision. There was no difference in RFS, MFS, OS, or CSS when comparing bladder cuff excision, other techniques, and no excision.

Bladder cuff excision improves recurrence-free survival, particularly when considering bladder recurrence. This benefit is conferred regardless of technique, as long as the intramural ureter and ureteral orifice are excised. However, the benefit of bladder cuff excision on metastasis-free, overall, and cancer-specific survival is unclear.

Radical nephroureterectomy (RNU) with bladder cuff resection is the standard treatment in patients with high-risk upper tract urothelial cancer (UTUC). However, it is unclear which specific surgical technique may lead to improve oncological outcomes in term of intravesical recurrence (IVR) in patients with UTUC.

To evaluate the efficacy of surgical techniques and approaches of RNU in reducing IVR in UTUC patients.

Three databases were queried in January 2024 for studies analyzing UTUC patients who underwent RNU. The primary outcome of interest was the rate of IVR among various types of surgical techniques and approaches of RNU.

Thirty-one studies, comprising 1 randomized controlled trial and 1 prospective study, were included for a systematic review and meta-analysis. The rate of IVR was significantly lower in RNU patients who had an early ligation (EL) of the ureter compared to those who did not (HR: 0.64, 95% CI: 0.44-0.94, p = 0.02). Laparoscopic RNU significantly increased the IVR compared to open RNU (HR: 1.28, 95% CI: 1.06-1.54, p < 0.001). Intravesical bladder cuff removal significantly reduced the IVR compared to both extravesical and transurethral bladder cuff removal (HR: 0.65, 95% CI: 0.51-0.83, p = 0.02 and HR: 1.64, 95% CI: 1.15-2.34, p = 0.006, respectively).

EL of the affected upper tract system, ureteral management, open RNU, and intravesical bladder cuff removal seem to yield the lowest IVR rate in patients with UTUC. Well-designed prospective studies are needed to conclusively elucidate the optimal surgical technique in the setting of single post-operative intravesical chemotherapy.

Prolonged laparoscopic nephroureterectomy (LNU) for upper tract urothelial cancer (UTUC) can increase the frequency of intravesical recurrence after surgery. Therefore, it is important for urological surgeons to have knowledge on preoperative risk factors for prolonged LNU. However, few studies have investigated the risk factors for prolonged LNU. We hypothesized that the quantity of perirenal fat affects the pneumoretroperitoneum time (PRT) of retroperitoneal LNU (rLNU). This study aimed to investigate the preoperative risk factors for prolonged PRT during rLNU.

We reviewed the data of 115 patients who underwent rLNU for UTUC between 2013 and 2021. The perirenal fat thickness (PFT) observed on preoperative computed tomography (CT) images was used to evaluate the perinephric fat quantity. Preoperative risk factors for PRT during rLNU were analyzed using logistic regression models. The cutoff value for PRT was determined based on the median time.The cutoff values for fat-related factors influencing PRT were defined according to receiver operating characteristic curve analysis.

The median PRT for rLNU was 182 min (interquartile range, 155-230 min). The cutoff values of posterior, lateral, and anterior PFTs were 15 mm, 24 mm, and 6 mm, respectively. Multivariate analysis revealed that a posterior PFT ≥ 15 mm (odds ratio [OR], 2.72; 95% confidence interval, 1.04-7.08; p = 0.0410) was an independent risk factor for prolonged PRT.

Thick posterior PFT is a preoperative risk factor for prolonged PRT during rLNU. For patients with UTUC and thick posterior PFT, surgeons should develop optimal surgical strategies, including the selecting an expert surgeon as a primary surgeon and the selecting transperitoneal approach to surgery or open surgery.

We aimed to assess the effectiveness of early single intravesical administration of epirubicin in preventing intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

Patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy between November 2018 and May 2022 were retrospectively reviewed. Intravesical epirubicin was administered within 48 hours if no evidence of leakage was observed. Epirubicin (50 mg) in 50 mL normal saline solution was introduced into the bladder via a catheter and maintained for 60 minutes. The severity of adverse events was graded using the Clavien-Dindo classification. We compared intravesical recurrence rate between the two groups. Multivariate analyses were performed to identify the independent predictors of bladder recurrence following radical nephroureterectomy.

Epirubicin (n=55) and control (n=116) groups were included in the analysis. No grade 1 or higher bladder symptoms have been reported. A statistically significant difference in the intravesical recurrence rate was observed between the two groups (11.8% at 1 year in the epirubicin group vs. 28.4% at 1 year in the control group; log-rank p=0.039). In multivariate analysis, epirubicin instillation (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20 to 0.93; p=0.033) and adjuvant chemotherapy (HR, 0.29; 95% CI, 0.13 to 0.65; p=0.003) were independently predictive of a reduced incidence of bladder recurrence.

This retrospective review revealed that a single immediate intravesical instillation of epirubicin is safe and can reduce the incidence of intravesical recurrence after radical nephroureterectomy. However, further prospective trials are required to confirm these findings.

Radical nephroureterectomy with concurrent bladder cuff excision (RNUBCE) is the gold standard surgical approach for high-risk primary upper tract urothelial carcinoma (UTUC). Given the notably high incidence of bladder tumor recurrence following this procedure, this study aimed to evaluate the effect and safety of intraoperative mitomycin-C (MMC) instillation vs. deferred instillation on overall oncological outcomes following robot-assisted RNUBCE.

This is a retrospective chart review study. Patients with non-invasive (N0, not T3/T4) UTUC who underwent robotic RNUBCE combined an intraoperative MMC instillation or a deferred MMC instillation after surgery at a medical center in Taiwan between November 2013 and June 2020 were eligible for inclusion. Patients with prior bladder UC, carcinomas of other origins, received neoadjuvant chemotherapy, and had undergone kidney transplantation were excluded. All surgeries were executed by a single surgical team under the guidance of the same surgeon. The primary outcomes was the risk of bladder tumor recurrence between patients received intraoperative (IO) vs. deferred MMC instillation postoperatively (PO) during one-year follow-up. The secondary outcome was postoperative adverse events assessed by the Clavien-Dindo classification. Univariate and multivariable Cox regression analyses were performed to determine the associations between study variables and the outcomes.

A total of 54 patients were included in the analysis. 12 (22.2%) patients experienced a bladder tumor recurrence during follow-up (IO: 7.7%, PO: 35.7%, p < 0.021). After adjustment in the multivariable, intraoperative MMC instillation was significantly associated with lower risk of bladder recurrence [adjusted hazard ratio (aHR) = 0.15, 95% CI: 0.03-0.81, p = 0.028]. No MMC-related Clavien-Dindo Grade III-IV adverse events were found in either group.

IIntraoperative MMC instillation is safe and associated with a lower bladder tumor recurrence risk in patients undergoing robotic RNUBCE for UTUC than deferred instillation. Future large, prospective studies are still warranted to confirm the findings.

This article is an English translation of the Clinical Practice Guidelines for Upper Tract Urothelial Carcinoma (2nd edition) published in June 2023. The Japanese Urological Association's (JUA) Guidelines Committee on Upper Tract Urothelial Carcinoma (UTUC) created a 2023 update guideline to support clinicians' current evidence-based management of UTUC and to incorporate its recommendations into clinical practice. The new guideline adhered as closely as possible to the Minds Manual for Guideline Development 2020 ver. 3.0. Findings related to epidemiological, pathological, diagnosis, treatment, and follow-up were reviewed. In addition, seven clinical questions (CQs) were set to determine the grade of recommendation and level of evidence. Preconceptions and biases were removed from the preparation process, the overall evidence was evaluated appropriately, and recommendations were made after fully considering the balance between benefits and harms. Although the evidence is still insufficient to be taken up as a CQ, the latest important information is described in seven columns, and clinical issues that should be resolved in the future related to the CQ are described as recommendations for tomorrow. We hope that these guidelines will help medical professionals, patients, and their families involved in the treatment of UTUC in their decision-making, and hope that a critical review of these guidelines will lead to further refinements in the next edition.

Radical nephroureterectomy (RNU) is the primary treatment strategy for upper tract urothelial carcinoma (UTUC). However, the intravesical recurrence occurs in 20-50% of all patients. The specific effect of subsequent bladder cancer (SBCa) on survival remains unclear. Therefore, we investigated the effect of SBCa following RNU in patients with UTUC.

PubMed, EMBASE, and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between SBCa and without SBCa. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3).

Five studies involving 2057 patients were selected according to the predefined eligibility criteria. Meta-analysis of cancer-specific survival (CSS) and overall survival (OS) revealed no significant differences between the SBCa and non-SBCa groups. However, subgroup analysis of pT0-3N0M0 patients suggested that people with SBCa had worse CSS (HR = 5.13, 95%CI 2.39-10.98, p < 0.0001) and OS (HR = 4.00, 95%CI 2.19-7.31, p < 0.00001).

SBCa appears to be associated with worse OS in patients with early stage UTUC. However, caution must be taken before recommendations are made because this interpretation is based on very few clinical studies and a small sample size. Research sharing more detailed surgical site descriptions, as well as enhanced outcome data collection and improved reporting, is required to further investigate these nuances.

The best approach of the bladder cuff (i.e., transvesical, extravesical, endoscopic) during radical nephroureterectomy (RNU) remains an unsolved question. The aim of this review is to compare the oncological and perioperative outcomes among three different approaches of the distal ureter during RNU.

A literature search was conducted through June 2022 using PubMed/Medline, Embase, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. The primary outcome was bladder recurrence-free survival and secondary outcomes included: perioperative outcomes, metastasis-free survival, and cancer-specific survival.

A total of 19 non-randomized studies comprising 6581 patients met our inclusion criteria. The risk of bladder recurrence, metastasis and cancer-related death did not differ significantly between each approach (all P>0.05). In subgroup analysis excluding patients with history of bladder cancer, the risk of bladder recurrence remained similar between each approach (all P>0.05). There was no significant difference in terms of operative time, estimated blood loss, length of hospital stay, and postoperative complications between each approach (all P>0.05). The main limitation is the retrospective design of 18/19 included studies.

The present systematic review and meta-analysis highlights the lack of high-level evidence on distal ureter management during RNU. On the basis of the available data, the present review supports the equivalence of different techniques of bladder cuff excision during RNU. The extravesical approach seems non-inferior to the transvesical approach in terms of oncological and perioperative outcomes.

Upper tract urothelial carcinoma (UTUC) poses unique challenges in diagnosis and treatment. This comprehensive review focuses on prophylactic intravesical therapy for UTUC, summarizing key aspects of intravesical therapy in various clinical scenarios, including concurrent with or following radical nephroureterectomy, kidney-sparing surgery, ureteroscopy-guided biopsy. The incidence of intravesical recurrence in UTUC after surgical treatment is significant, necessitating effective preventive measures. Intravesical therapy plays a vital role in reducing the risk of bladder recurrence following UTUC surgery. Tailoring timing, drug selection, dosage, and frequency is vital in optimizing treatment outcomes and reducing intravesical recurrence risk in UTUC. This review provides a comprehensive summary of the history, clinical trials, guideline recommendations, and clinical applications of intravesical therapy for UTUC. It also discusses the future directions based on current clinical needs and ongoing trials. Future directions entail optimizing dosage, treatment duration, and drug selection, as well as exploring novel agents and combination therapies. Intravesical therapy holds tremendous potential in improving outcomes for UTUC patients and reducing the risk of bladder recurrence. Although advancements have been made in UTUC treatment research, further refinements are necessary to enhance efficacy and safety.

This study aimed to establish and validate nomograms to predict the probability of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper urinary tract epithelial carcinoma (UTUC).

Clinical data of 528 patients with UTUC after RNU were collected from two medical centers between 2009 and 2020. We used the least absolute shrinkage and selection operator (LASSO) regression to select variables for multivariable Cox regression analysis in the training cohort and included independent risk factors into nomogram models predicting IVR-free survival (IVRFS). Another center was applied as the external cohort to validate the predictive accuracy and discriminative ability of the nomogram by performing area under the receiver operating curve (AUC), consistency index (C-index), and calibration curve.

History of bladder cancer, tumor size, preoperative urine cytology, postoperative instillation, Ki-67, and platelet-to-lymphocyte ratio (PLR) were identified as independent risk factors for IVR. The prognosis model including these predictors demonstrated excellent discriminatory performance in both the training cohort (C-index, 0.814) and external validation cohort (C-index, 0.748). The calibration plots of the nomogram revealed good consistency in both cohorts. Finally, patients could be classified into two risk groups based on scores obtained from the nomogram, with significant differences in IVRFS.

Our study provided a reliable nomogram for predicting the probability of IVR in patients with UTUC after RNU. Risk stratification based on this model may assist urologists make optimal clinical decisions on the management of UTUC.

The European Association of Urology (EAU) guidelines panel on upper urinary tract urothelial carcinoma (UTUC) has updated the guidelines to aid clinicians in evidence-based management of UTUC.

To provide an overview of the EAU guidelines on UTUC as an aid to clinicians.

The recommendations provided in these guidelines are based on a review of the literature via a systematic search of the PubMed, Ovid, EMBASE, and Cochrane databases. Data were searched using the following keywords: urinary tract cancer, urothelial carcinomas, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, (neo)adjuvant treatment, instillation, recurrence, risk factors, metastatic, immunotherapy, and survival. The results were assessed by a panel of experts.

Even though data are accruing, for many areas there is still insufficient high-level evidence to provide strong recommendations. Patient stratification on the basis of histology and clinical examination (including imaging) and assessment of patients at risk of Lynch syndrome will aid management. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk UTUC and two functional kidneys. In particular, for patients with high-risk or metastatic UTUC, new treatment options have become available. In high-risk UTUC, platinum-based chemotherapy after radical nephroureterectomy, and adjuvant nivolumab for unfit or patients who decline chemotherapy, are options. For metastatic disease, gemcitabine/carboplatin chemotherapy is recommended as first-line treatment for cisplatin-ineligible patients. Patients with PD-1/PD-L1-positive tumours should be offered a checkpoint inhibitor (pembrolizumab or atezolizumab).

These guidelines contain information on the management of individual patients according to the current best evidence. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen according to the risk stratification of these tumours.

Cancer of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, timely and appropriate diagnosis is most important. A number of known risk factors exist.

Upper tract urothelial carcinoma (UTUC) is a relatively rare, but highly malignant, disease with an estimated annual incidence of 2 cases per 100,000 people. The main surgical treatment modalities for UTUC are radical nephroureterectomy (RNU) with bladder cuff resection. After surgery, intravesical recurrence (IVR) can occur in up to 47% of patients, and 75% of them present with non-muscle invasive bladder cancer (NMIBC). However, there are few studies focused on the diagnosis and treatment of postoperatively recurrent bladder cancer for patients with previous UTUC history (UTUC-BC), and many of the influencing factors are still controversial. In this article, we performed a narrative review of the recent literature, mainly summarizing the factors influencing postoperative IVR in patients with UTUC and discussing the subsequent prevention, monitoring, and treatment tools for it.

Nephroureterectomy(NU) remains the gold-standard surgical option for the management of upper urinary tract urothelial carcinoma(UTUC). Controversy exists regarding the optimal excision technique of the lower ureter. We sought to compare post-UTUC bladder tumour recurrence across the Scottish Renal Cancer Consortium(SRCC).

Patients who underwent NU for UTUC across the SRCC 2012-2019 were identified. The impact of lower-end surgical technique along with T-stage, N-stage, tumour location and focality, positive surgical margin, pre-NU ureteroscopy, upper-end technique and adjuvant mitomycin C administration were assessed by Kaplan-Meier and Cox-regression. The primary outcome was intra-vesical recurrence-free survival (B-RFS).

In 402 patients, the median follow-up was 29 months. The lower ureter was managed by open transvesical excision in 90 individuals, transurethral and laparoscopic dissection in 76, laparoscopic or open extra-vesical excision in 31 and 42 respectively, and transurethral dissection and pluck in 163. 114(28.4%) patients had a bladder recurrence during follow-up. There was no difference in B-RFS between lower-end techniques by Kaplan-Meier (p = 0.94). When all factors were taken into account by adjusted Cox-regression, preceding ureteroscopy (HR 2.65, p = 0.001), lower ureteric tumour location (HR 2.16, p = 0.02), previous bladder cancer (HR 1.75, p = 0.01) and male gender (HR 1.61, p = 0.03) were associated with B-RFS.

These data suggest in appropriately selected patients, lower ureteric management technique does not affect B-RFS. Along with lower ureteric tumour location, male gender and previous bladder cancer, preceding ureteroscopy was associated with a higher recurrence rate following NU, and the indication for this should be carefully considered.

To show the effect of a 6-month (4 times weekly followed by 5 times monthly) maintenance mitomycin C regimen on the prevention of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).

A total of 119 patients undergoing a RNU between 2007 and 2021 in a single center hospital were retrospectively reviewed. A total of 66 patients were eligible for further analysis. 27 patients received no post-operative MMC (median follow-up: 110 months) and 39 patients received a 6-month (4 times weekly, 5 times monthly) maintenance regimen of MMC (median follow up: 48 months). The primary outcome was the 1-, 2- and 5-year bladder recurrence free survival (BRFS).

There was a significant difference (p = 0.001) in BRFS between the two groups. The 1-, 2, and 5-year BRFS for the MMC- group was 67%, 63% and 43%, respectively. The 1-, 2- and 5-year BRFS for the MMC + group was 95%, 86% and 86%, respectively. Univariate analysis showed no other potential prognostic factors that had a significant effect on the BRFS.

A 6-month maintenance schedule of MMC is effective at significantly reducing the risk of IVR after RNU for UTUC. We could not find any other significant prognostic factors to predict IVR.

Intravesical recurrence (IVR) after nephroureterectomy for upper tract urothelial carcinoma (UTUC) is relatively frequent, occurring in about 30-50% of patients. The aim of this study was to investigate the differences of the prognosis and IVR between open and laparoscopic surgery and to elucidate the risk factor of IVR.

We retrospectively analyzed data from 403 patients with UTUC treated with laparoscopic or open nephroureterectomy at six affiliated hospitals between 1990 and 2015. The clinicopathological factors of each group were examined using Kaplan-Meier plots, and univariate and multivariate analyses.

There was no difference in recurrence and cancer-specific mortality between open and laparoscopic surgery in univariate and multivariate analyses. There was no significant difference in IVR rate between the laparoscopic and open groups (p = .22). Among the patients with IVR, 84% of patients relapsed within 2 years. Univariate analysis of IVR showed a significant increase in patients with low-grade (p = .03, HR = 1.64) or low-stage urothelial carcinoma (pT1 or lower, p = .006, HR = 1.77) with no lymph node involvement (p = .002, HR = 10.3) or lymphovascular invasion (p = .009, HR = 1.79). Surgical modality was not an independent factor. In multivariate analysis, there was no independent predictive factor for IVR.

There was no difference in recurrence, cancer-specific mortality, and IVR between open and laparoscopic surgery. On the other hand, our results suggested that the low malignant potential tumor may be a risk factor for IVR. This finding provides insight into IVR, which may help with the development of personalized prevention and treatment strategies.

Bladder recurrences have been reported in 22-47% of patients after surgery for upper urinary tract urothelial carcinoma (UTUC). This collaborative review focuses on risk factors for and treatment strategies to reduce bladder recurrences after upper tract surgery for UTUC.

To review the current evidence on risk factors and treatment strategies for intravesical recurrence (IVR) after upper tract surgery for UTUC.

This collaborative review is based on a literature search of PubMed/Medline, Embase, Cochrane Library, and currently available guidelines on UTUC. Relevant papers on bladder recurrence (etiology, risk factors, and management) after upper tract surgery were selected. Special attention has been paid to (1) the genetic background of bladder recurrences, (2) bladder recurrences after ureterorenoscopy (URS) with or without a biopsy, and (3) postoperative or adjuvant intravesical instillations. The literature search was performed in September 2022.

Recent evidence supports the hypothesis that bladder recurrences after upper tract surgery for UTUC are often clonally related. Clinicopathologic risk factors (patient, tumor, and treatment related) have been identified for bladder recurrences after UTUC diagnosis. Specifically, the use of diagnostic ureteroscopy before radical nephroureterectomy (RNU) is associated with an increased risk of bladder recurrences. Further, a recent retrospective study suggests that performing a biopsy during ureteroscopy may further worsen IVR (no URS: 15.0%; URS without biopsy: 18.4%; URS with biopsy: 21.9%). Meanwhile, a single postoperative instillation of intravesical chemotherapy has been shown to be associated with a reduced bladder recurrence risk after RNU compared with no instillation (hazard ratio 0.51, 95% confidence interval 0.32-0.82). Currently, there are no data on the value of a single postoperative intravesical instillation after ureteroscopy.

Although based on limited retrospective data, performing URS seems to be associated with a higher risk of bladder recurrences. Future studies are warranted to assess the influence of other surgical factors as well as the role of URS biopsy or immediate postoperative intravesical chemotherapy after URS for UTUC.

In this paper, we review recent findings on bladder recurrences after upper tract surgery for upper urinary tract urothelial carcinoma.

To report contemporary epidemiological data and treatment trends for upper tract urothelial carcinoma (UTUC) in Germany over a 14-year period.

We analyzed data from the nationwide German hospital billing database and the German cancer registry from 2006 to 2018/2019. The significance of changes over time was evaluated via regression analysis. Survival outcomes were calculated using the Kaplan-Meier method.

There was a non-significant increase in the age-standardized incidence rate from 2.5/100,000 in 2006 to 2.9/100.000 in 2018. 13% of patients presented with lymph node metastasis and 7.6% of patients presented with distant metastasis at primary diagnosis. The 5-year overall survival was estimated at 45% and the 10-year overall survival at 32%. Endoscopic biopsies of the renal pelvis and ureter as well as ureteroscopies with excision/destruction of UTUC all increased significantly over the study period. The number of radical nephroureterectomies (RNU) for UTUC steadily increased from 1643 cases in 2006 to 2238 cases in 2019 (p < 0.005) with a shift from open surgery towards minimally invasive surgery. Complex reconstructive procedures like ileal ureter replacement or autotransplantation are rarely performed for urothelial carcinoma of the ureter.

Diagnostic and therapeutic procedures for UTUC have increased and minimally invasive nephroureterectomy is the predominant approach concerning radical surgery in 2019.

Several groups proved kidney-sparing surgery (KSS) had equivalent oncological outcomes compared with radical nephroureterectomy (RNU) for the low-risk upper urinary tract urothelial carcinoma (UTUC) patients. Whereas, the clinical efficacy of KSS for high-risk UTUC, especially for distal high-risk ureteral carcinoma, remains unclear.

To evaluate the feasibility of KSS for patients with distal high-risk ureter cancer.

Our study included 22 patients who diagnose the distal high-risk ureter cancer and underwent KSS between May 2012 and July 2021 in the First Affiliated Hospital of Chongqing Medical University. Overall survival (OS), confirmed as the primary endpoint of present study, was assessed by a blinded independent review committee (BIRC). The secondary endpoints included the postoperative SF-36 (the short form 36 health survey questionnaire) score, progression-free survival (PFS), postoperative complications, and so on.

Overall, 17 (77.3%) and 5 (22.7%) patients underwent segmental ureterectomy (SU) and endoscopic ablation (EA), respectively. By the cut-off date, the mean OS was 76.3 months (95% Cl: 51.3-101.1 months) and the mean PFS was 47.0 months (95% Cl: 31.1-62.8 months), respectively. And the SF-36 score in a majority of patients was >300 (90.9%).

This is a daring endeavor to explore the clinical efficacy of KSS in distal high-risk ureter cancer based on the high-risk UTUC criteria, which shows satisfactory results in the long-term prognosis and operation-associated outcomes. However, future randomized or prospective multicenter studies are necessary to validate our conclusions.

The aim was to propose an update of the French Urology Association Cancer Committee (ccAFU) Recommendations on the management of upper urinary tract urothelial carcinomas (UUT-UC).

A systematic Medline search was performed between 2020 and 2022, taking account of the diagnosis, treatment options and follow-up of UUT-UC, while evaluating the references with their levels of evidence.

The diagnosis of this rare pathology is based on CTU acquisition during excretion and flexible ureterorenoscopy with histological biopsies. Radical nephroureterectomy (RNU) remains the gold standard for surgical treatment. Nevertheless conservative treatment can be discussed for low risk lesions: tumour of low-grade, with no infiltration on imaging, unifocal<2cm, eligible for full treatment therefore requiring close endoscopic surveillance by flexible ureteroscopy in compliant patients. After RNU, postoperative instillation of chemotherapy is recommended to reduce the risk of recurrence in the bladder. Adjuvant chemotherapy has shown clinical benefits compared to surveillance after RNU for tumours (pT2-T4 N0-3 M0).

These updated recommendations should contribute to improving not only patients' level of care, but also the diagnosis and decision-making concerning treatment for UUT-UC.