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Background: The urinary tract is one of the most frequently involved organs in advanced non-urologic pelvic malignances. Extensive resection of ureteric organs is mandatory during a curative surgery. Urinary reconstruction after partial ureterectomy, the most challenging situation, is associated with a higher incidence of complication than cystectomy, especially when performed with laparoscopy. Furthermore, to date, no generally accepted strategy for urinary reconstruction after extensive tumor resection with partial ureterectomy has been established., Methods: The study identified and scrutinized intraoperative videos and clinical records of patients with locally advanced or recurrent pelvic malignancies who underwent segmental ureterectomy during en bloc resection of advanced tumors between February 2020 and February 2024., Results: The study enrolled nine patients, including four cases managed by ureteroureteral anastomosis, two cases managed by ureteroneocystomy, two cases managed by Boari flap reconstruction, and one case managed by ileal interposition. In all nine cases, R0 margins were obtained, and no case needed conversion to laparotomy. No clinical evidence of postoperative urinary leakage was identified. The median follow-up period was 14 months (range, 5-19 months). In three of the nine cases, recurrence was identified, at the 3rd, 18th, and 19th month follow-up evaluations, respectively. One patient died of systemic metastasis., Conclusions: Laparoscopic ureteric reconstruction is feasible for patients who undergo segmental ureterectomy during extensive surgery for locally advanced or recurrent pelvic malignancies. A low anastomotic leakage rate and favorable postoperative renal function could be achieved in this study when anastomosis was performed laparoscopically., (© 2024. Society of Surgical Oncology.)

Objectives: We sought to determine whether bladder cuff excision and its technique influence outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Methods and Materials: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the classification and prognostic effects of a 2 cm tumor size in patients with ureteral cancer (UC) undergoing segmental ureterectomy (SU)., Patients and Methods: A total of 75 patients with UC who underwent SU in our hospital between April 2013 and April 2023 were included in this study. The study population was grouped based on tumor size, which was defined as the maximum diameter of the pathological specimens, resulting in 30 patients (40.0%) with tumor size <2 cm and 45 patients (60.0%) with tumor size ≥2 cm. The clinicopathological variables, perioperative parameters, and oncological outcomes were compared between the 2 groups. The endpoints were recurrence-free survival (RFS), and cancer-specific survival (CSS)., Results: A tumor ≥2 cm was related to a higher positive rate of urine exfoliative cytology (P = 0.049) and fewer preoperative ureteroscopies (P = 0.033) than tumors <2 cm. After a follow-up of 6.3 to 128.7 months (median 40.2 months), 23 cases (30.7%) experienced recurrence and 11 patients (14.7%) succumbed to UC in the end. Compared to those with tumor size <2 cm, patients with tumor size ≥2 cm experienced more urothelial recurrence (P = 0.032). Kaplan-Meier analysis demonstrated that patients with tumor size ≥2 cm displayed inferior urothelial RFS than those with tumor size <2 cm (P = 0.026). Multivariate Cox analysis identified tumor size ≥2 cm, and pathological stage ≥T2 were significant prognostic factors of poor urothelial RFS (all P < 0.05)., Conclusion: Tumor size ≥2 cm was associated with a high rate of urothelial recurrence and served as an independent prognostic factor of adverse urothelial RFS in SU-treated patients with UC. Patients are advised to select surgical treatments for UC following the EAU guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To perform a collaborative review of the literature exploring the microsatellite instability/deficient mismatch repair (MSI/dMMR) phenotype in patients with upper tract urothelial carcinoma (UTUC)., Method: A collaborative review of the literature available on Medline was conducted by the Cancer Committee of the French Association of Urology to report studies describing the genetic mechanisms, investigation, prevalence and impact of the MSI/dMMR phenotype in UTUC patients., Results: The predominant genetic mechanism leading to the MSI/dMMR phenotype in UTUC patients is related to the constitutional mutation of one allele of the MMR genes MLH1, MSH2, MSH6 and PMS2 within Lynch syndrome. Indications for its investigation currently remain limited to patients with a clinical suspicion for sporadic UTUC to refer only those with a positive testing for germline DNA sequencing to screen for this syndrome. With regard to technical aspects, despite the interest of MSIsensor, only PCR and immunohistochemistry are routinely used to somatically investigate the MSI and dMMR phenotypes, respectively. The prevalence of the MSI/dMMR phenotype in UTUC patients ranges from 1.7% to 57%, depending on the study population, investigation method and definition of a positive test. Younger age and a more balanced male to female ratio at initial diagnosis are the main specific clinical characteristics of UTUC patients with an MSI/dMMR phenotype. Despite the conflicting results available in the literature, these patients may have a better prognosis, potentially related to more favourable pathological features. Finally, they may also have lower sensitivity to chemotherapy but greater sensitivity to immunotherapy., Conclusion: Our collaborative review summarises the available data from published studies exploring the MSI/dMMR phenotype in UTUC patients, the majority of which are limited by a low level of evidence., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

This study evaluates the survival outcomes of segmental ureterectomy (SU) combined with chemotherapy in patients with high-grade non-metastatic ureteral cancer (UC) using data from the SEER database. A total of 1757 patients with Grade III-IV non-metastatic UC were analyzed. Overall survival (OS) was assessed through Kaplan-Meier analysis, and independent prognostic factors were identified via Cox regression. A Nomogram model was developed and evaluated using the concordance index, area under the time-dependent ROC curve, calibration curves, and decision curve analysis. The 1-, 3-, and 5-year OS rates were 82.8%, 55.6%, and 42.8%, respectively. Age, treatment protocol, T stage, and N stage were significant prognostic factors. Both SU + chemotherapy and radical nephroureterectomy (RNU) + chemotherapy demonstrated comparable survival outcomes, outperforming surgery alone, particularly in patients aged 70 and older. The Nomogram demonstrated high predictive accuracy and clinical utility. These findings suggest that SU + chemotherapy offers survival benefits similar to RNU + chemotherapy, making it a viable option, especially for elderly patients or those with impaired renal function., (© 2024. The Author(s).)

Purpose: To assess the impact of neoadjuvant and adjuvant chemotherapy on survival outcomes, within a large multicenter cohort of Upper tract urothelial carcinoma patients treated with Nephroureterectomy., Methods: A multicenter retrospective analysis utilizing the Robotic surgery for Upper Tract Urothelial Cancer Study registry was performed. Baseline, preoperative, perioperative, and pathologic variables of three groups of patients receiving surgery only, neoadjuvant or adjuvant chemotherapy were compared. Categorical and continuous variables among the three subgroups were compared with Chi square and ANOVA tests. The impact of perioperative chemotherapy on survival outcomes was assessed with the Kaplan Meier method. Univariable and multivariable Cox regression analyses were performed to identify predictors of survival., Results: Overall, 1,994 patients were included. Overall and Clavien grade ≥3 complications rates were comparable among the three subgroups (p = 0.65 and p = 0.92). At Kaplan Meier analysis, neoadjuvant chemotherapy significantly improved cancer-specific survival (p = 0.03) and overall survival (p = 0.03) probabilities of patients with cT ≥ 3 tumors and of those with positive cN (p = 0.03 and p = 0.02). On multivariable analysis, neoadjuvant chemotherapy was independently associated with an improvement of cancer-specific survival in cT ≥ 3 patients (HR 0.44; p = 0.04), and of both cancer-specific survival (HR 0.50; p = 0.03) and overall survival (HR 0.53; p = 0.02) probabilities in positive cN patients., Conclusions: This large multicenter retrospective analysis suggests significant survival benefit in Upper tract urothelial carcinoma patients with either locally advanced or clinically positive nodes disease receiving neoadjuvant chemotherapy. These findings can be regarded as "hypothesis generating", stimulating future trials focusing on such advanced stages., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Upper tract urothelial carcinoma (UTUC) is a cancer that is often already in an advanced stage at the time of initial diagnosis. Although urothelial carcinoma of the upper and lower urinary tracts both originate from the urothelium and have similar genetic alterations, there are significant differences in their distribution. In localized high-risk UTUC, radical nephroureterectomy is the gold standard therapy. In metastatic UTUC, major changes are emerging in sequential therapy due to the investigation of new classes of drugs. In addition to platinum-based combination chemotherapy and immunotherapy, new substances such as antibody-drug conjugates (ADCs) and FGFR inhibitors are used., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The purpose of this study was to test for survival differences according to adjuvant chemotherapy (AC) status in radical nephroureterectomy (RNU) patients with pT2-T4 and/or N1-2 upper tract urothelial carcinoma (UTUC)., Patients and Methods: Within the Surveillance, Epidemiology, and End Results database (SEER, 2007-2020), patients with UTUC treated with AC versus RNU alone were identified. Kaplan-Meier plots and multivariable Cox regression models addressed cancer-specific mortality (CSM)., Results: Of 1995 patients with UTUC, 804 (40%) underwent AC versus 1191 (60%) RNU alone. AC rates increased from 36.1 to 57.0% over time in the overall cohort [estimated annual percentage changes (EAPC) ± 4.5%, p < 0.001]. The increase was from 28.8 to 50.0% in TanyN0 patients (EAPC ± 7.8%, p < 0.001) versus 50.0-70.9% in TanyN1-2 patients (EAPC ± 2.3%, p = 0.002). Within 698 patients harboring TanyN1-2 stage, median CSM was 31 months after AC versus 16 months in RNU alone (Δ = 15 months, p < 0.0001) and AC independently predicted lower CSM [hazard ratio (HR) 0.64; p < 0.001]. Similarly, within subgroup analyses according to stage, relative to RNU alone, AC independently predicted lower CSM in T2N1-2 (HR 0.49; p = 0.04), in T3N1-2 (HR 0.72; p = 0.015), and in T4N1-2 (HR 0.49, p < 0.001) patients. Conversely, in all TanyN0 as well as in all stage-specific subgroup analyses addressing N0 patients, AC did not affect CSM rates (all p > 0.05)., Conclusions: In RNU patients, AC use is associated with significantly lower CSM in lymph-node-positive (N1-2) patients but not in lymph-node-negative patients (N0). The distinction between N1-2 and N0 regarding the effect of AC on CSM applied across all T stages from T2 to T4, inclusively., (© 2024. Society of Surgical Oncology.)

Current guidelines recommend radical nephroureterectomy with bladder cuff excision as the standard surgical treatment for high-risk upper tract urothelial carcinoma (UTUC). While large evidence is available regarding open and laparoscopic nephroureterectomy, data focusing on robotic nephroureterectomy (RNU) in UTUC are mostly limited with mixed results, especially in locally advanced disease. In light of the recent introduction of new robotic platforms, it is of utmost importance to further investigate oncologic outcomes associated with RNU. Moreover, stronger data exploring different operative settings (i.e. robotic arms and trocars placement) for the new robotic systems are eagerly warranted. To give an answer to such open clinical questions, the Junior ERUS/Young Academic Urologist Working Group on Robot-assisted Surgery designed a multicentric project involving different high-volume centers across the world. The aim of the study will be exploring surgical and oncologic outcomes of RNU, specifically focusing on several clinical unmet needs, such as best operative setting for new robotic platforms, lymph node dissection (LDN) template and robotic bladder cuff management.

Background and Objective: Growing evidence supports the use of neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). However, the implications of residual UTUC at radical nephroureterectomy (RNU) after NAC are not well characterized. Our objective was to compare oncologic outcomes for pathologic risk-matched patients who underwent RNU for UTUC who either received NAC or were chemotherapy-naïve., Methods: We retrospectively identified 1993 patients (including 112 NAC recipients) who underwent RNU for nonmetastatic, high-grade UTUC between 1985 and 2022 in a large, international, multicenter cohort. We divided the cohort into low-risk and high-risk groups defined according to pathologic findings of muscle invasion and lymph node involvement at RNU. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) estimates were calculated using the Kaplan-Meier method. Multivariable analyses were performed to determine clinical and demographic factors associated with these outcomes., Key Findings and Limitations: Among patients with low-risk pathology at RNU, RFS, OS, and CSS were similar between the NAC and chemotherapy-naïve groups. Among patients with high-risk pathology at RNU, the NAC group had poorer RFS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 2.10-4.48), OS (HR 2.06, 95% CI 1.33-3.20), and CSS (subdistribution HR 2.54, 95% CI 1.37-4.69) in comparison to the pathologic risk-matched, chemotherapy-naïve group. Limitations include the lack of centralized pathologic review., Conclusions and Clinical Implications: Patients with residual invasive disease at RNU after NAC represent a uniquely high-risk population with respect to oncologic outcomes. There is a critical need to determine an optimal adjuvant approach for these patients., Patient Summary: We studied a large, international group of patients with cancer of the upper urinary tract who underwent surgery either with or without receiving chemotherapy beforehand. We identified a high-risk subgroup of patients with residual aggressive cancer after chemotherapy and surgery who should be prioritized for clinical trials and drug development., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Similar to bladder cancer, about one third of upper tract urothelial carcinoma (UTUC) present variant histology (VH). We aim to evaluate the incidence, clinical characteristics and the impact on outcomes of VH in UTUC., Methods: We consecutively enrolled 77 patients treated between 2009 and 2022 by radical surgery for UTUC from a secondary and a tertiary referral center. A pathology review of all specimens was performed by 1 independent uropathologist for each center. We compared pure UTUC and UTUC with VH and the accuracy of endoscopic biopsy. Descriptive and comparative analysis was performed to assess the association with clinical characteristics and the Kaplan-Meier estimator to compare outcomes., Results: Median follow-up after surgery was 51 months. VH was present in 21/77 (28%) patients and 4/21 (19%) patients had multiple variants. The most frequent VH was squamous 12/21 (57%), followed by glandular 7/21 (33%) and micropapillary 3/21 variants (14%). Neuroendocrine carcinoma was present in 2 patients. Nested variant was found in 1 patient. Muscle invasive tumor (≥pT2) was present in 30/56 (54%) patients with pure UTUC and in 18/21 (86%) patients with VH (P < 0.05). Presence of carcinoma in situ was seen in 24/56 (43%) patients with pure UTUC and in 16/21 (76%) with VH (P < 0.05). Cumulative 8/56 (14%) with pure UTUC had a nonintravesical recurrence (6 patients with local and 2 distant recurrence) compared to 8/21 (38%) (3 local, 3 nodal, 2 distant) in the subgroup with VH (P < 0.05). Opposite effect was noted for bladder recurrence: 60% for pure UTUC vs. 29% for tumors with VH (P < 0.05). Review of preoperative endoscopic biopsy did not show the presence of VH in any patients. Differences in outcomes did not reach significance: 3yr-OS 63% vs. 42% (P 0.28) and 3yr-CSS 77% vs. 50% (P 0.7)., Conclusion: Almost a third of UTUC present VH. Presence of VH is related to more aggressive tumor characteristics and associated with unfavorable outcomes. Due to a higher rate of extravesical recurrences in UTUC with VH, Follow-up controls should include cross sectional imaging and cystoscopy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Fibroepithelial polyps in the urinary tract are a rare cause of obstructive uropathy with fewer than 130 cases reported in the literature. In our series, we describe polyps that were missed on preoperative imaging and later found in the operating room during pyeloplasty. It is critical for urologists to be aware of polyps as a potential source of obstruction as they can increase the complexity of a reconstruction and, if missed, may result in a failed repair and persistent obstruction. We hypothesize that performing a retrograde pyelogram prior to ureteric reconstruction will facilitate diagnosis prior to surgical repair., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to report. No color figures will be needed for this submission., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.

Objective: We aimed to evaluate the expression of HER2 in patients with upper tract urothelial carcinoma (UTUC) in Southwest China by using a relatively large cohort, and to determine the relationship between HER2 expression and clinicopathological characters., Materials and Methods: We retrospectively enrolled the clinical data of 155 UTUC patients who have undergone radical nephroureterectomy (RNU) from March 2019 to September 2022. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest (Scores of 0 or 1 + were considered as negative and 2 + or 3 + as positive). Tumor molecular phenotype was classified by the panel of CK20, CK5/6, and CD44., Results: HER2 was overexpressed in 55 (35.5%) patients. It was associated with pathologic characteristics such as grade (p = 0.017), tumor molecular phenotype (p < 0.001) and Ki-67 expression (p = 0.017). On univariate and multivariable logistic regression analysis, HER2 overexpression remained associated with higher grade (HR, 10.6; 95% CI 1.0-112.6; p = 0.050) and luminal molecular phenotype (HR, 8.0; 95% CI 1,6-38.4; p = 0.010). During disease progression after nephroureterectomy, the phenotype of the tumor might change and a switch phenomenon in phenotype after recurrence in the bladder was reported., Conclusion: According to our study, in Southwest China, one-third of UTUC patients overexpressed HER2. Tumors with high grade or luminal phenotype tended to be HER2 positive. HER2 may represent a promising target for therapy in UTUC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We aimed to investigate the effect of the haemoglobin, albumin, lymphocyte and platelet (HALP) score on pathologic results and bladder cancer recurrence (BCR) in patients operated for upper urinary tract tumours (UTUCs)., Material and Methods: HALP scores of all patients were calculated. Demographic data, preoperative blood parameters, pathologic data and the BCR development status of patients with low and high HALP scores were compared., Results: Haemoglobin (11.2±2.3 g/dL vs. 12.9±2.4 g/dL), albumin (4.0±0.8 g/dL vs. 4.4±0.9 g/dL) and HALP score (38.2±2.9 vs. 43.4±3.1) were statistically lower in the BCR (+) group compared with the BCR (-) group (p<0.001). The ROC curve showed that the optimal cut-off point for the HALP score was 40.8. Multivariate analyses showed that the HALP score was effective on Tumour Grade, Tumour Stage, BCR., Conclusion: We have shown that patients with lower HALP scores have a more advanced stage and higher-grade pathologic outcomes and have a higher risk of developing BCR., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction and Objective: Kidney-sparing surgery (KSS) for upper tract urothelial cancer (UTUC) has gained increasing interest recently. However, there is limited contemporary data regarding the role of KSS in ureteral urothelial carcinoma. Therefore, we investigated the survival outcomes of ureteral urothelial carcinoma after KSS from a large, prospective international UTUC registry. Methods: The Clinical Research Office of the Endourology Society-Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry included patients with UTUC who received KSS or radical nephroureterectomy (RNU) between 2014 and 2019. In this study, we included patients with ureteral UTUC only. Study outcomes included overall survival (OS), cancer-specific survival (CSS), upper tract recurrence-free survival (RFS), intravesical RFS, progression-free survival (PFS), and metastasis-free survival (MFS). Propensity score matching (PSM) was performed to balance the tumor features' differences between groups. Results: Of the 391 patients with ureteral UTUC, 309 (79.0%) received RNU and 82 (21.0%) received KSS by ureteroscopy with laser ablation ( n = 28) or segmental resection ( n = 54). After PSM, there were no differences in OS ( p = 0.525), CSS ( p = 0.487), upper tract RFS ( p = 0.147), intravesical RFS ( p = 0.989), PFS ( p = 0.617), and MFS ( p = 0.336) between KSS and RNU. There were no significant differences between ureteroscopic ablation and segmental resection in OS, CSS, intravesical RFS, PFS, and MFS with RNU. Proximal ureteral UTUC had worse OS and CSS outcomes than other tumor locations following segmental resection. Conclusions: In patients with ureteral UTUC, no significant differences in long-term survival outcomes were observed between KSS and RNU. Proximal ureteral UTUC had worse survival outcomes over other tumor locations following segmental resection.

Purpose: To evaluate the efficacy of intravesical (IVe) Bacillus Calmette-Guerin (BCG) to treat non-muscle invasive bladder cancer (NMIBC) recurrences in patients who have previously undergone nephroureterectomy for upper tract urothelial carcinoma (UTUC)., Methods: We performed a single institution retrospective review of patients who underwent nephroureterectomy for UTUC from 2009 to 2021. Patients who subsequently developed NMIBC treated with transurethral resection followed by IVe BCG were included in the study group. A control cohort was formed by retrospective review of patents with primary NMIBC treated with BCG during the same period. Patients in the control cohort were matched by stage of bladder cancer at a 2:1 ratio of control to study subjects. Demographic data, pathology of bladder tumors prior to and following BCG, use of maintenance BCG (mBCG), time to recurrence, time to progression, progression to cystectomy, and progression to metastatic disease were collected on all patients. Descriptive statistics were utilized to compare the 2 groups. The primary outcome was progression to muscle invasive disease. Secondary outcomes included intravesical recurrence free survival, disease free survival, and progression to metastatic disease. Univariable and multivariable logistic regression analysis was performed to elucidate independent variables associated with bladder tumor recurrence. Multivariable Cox regression analysis was used to assess the impact of prior UTUC on time to bladder tumor recurrence., Results: One-hundred and ninety-one patients underwent nephroureterectomy at our institution from 2009 to 2021 for UTUC. Twenty-five patients were identified to have subsequently developed NMIBC recurrences treated with inductions BCG. The control group was comprised of 50 patients with primary NMIBC matched by stage of bladder cancer for which BCG was indicated in the study group. Median (interquartile range [IQR]) follow-up was significantly longer in the control group relative to the study group (64.8 [50.1-85.6] vs 25 months [17-35]; P = 0.001). There were no significant differences in demographics between the study and control groups. The rate of progression to muscle invasive disease was 17% vs 0% in the study group and control group respectively (P = 0.0521). History of UTUC was associated with increased risk of intravesical bladder tumor recurrence post BCG on multivariable analysis (HR 2.5; P = 0.017) and Kaplan Meier survival analysis (P = 0.039). The mean time to bladder tumor recurrence after treatment with BCG was significantly worse in the study group at (7.9 vs. 23.9 months; P = 0.0322). Similarly, the rate of progression to metastatic disease was worse in the study group (24% vs 2%; P = 0.0047). Overall disease-free survival was also noted to be significantly worse on Kaplan Meier survival analysis in the study group (P = 0.0074). No statistically significant differences in the stage grade of bladder tumor recurrence, grade of bladder tumor recurrence, or rate of progression to cystectomy were identified., Conclusions: Our study suggests reduced efficacy of BCG for NMIBC in patients with a history of UTUC. Patients in this population should be counseled accordingly. Research into alternative treatments for bladder tumor recurrence and more aggressive prophylactic regimens after nephroureterectomy for prevention of bladder tumor recurrence in this population is encouraged., Competing Interests: Declaration of competing interest None of the authors have a conflict of interest with the submitted research. There were no funding sources for the research submitted. All listed authors have contributed significantly to the published research and reviewed the above manuscript. There was no use of artificial intelligence software in the writing or editing of the submitted research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery., Materials and Methods: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes., Results: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (P = 0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (P = 0.6), and MFS (P = 0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality., Conclusions: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Metastasis of malignant melanoma to urinary tract is reported to be rare. According to retrospective analysis of a single center study, improvement of overall survival was observed in patients with metastasis to the gastrointestinal tract that had undergone metastasectomy with curative intent. However, there is no significant evidence regarding resection for metastasis to urinary tract., Case Presentation: Case 1: an 86-year-old Japanese man was diagnosed with a small bladder tumor by computed tomography scan during post operative follow-up of malignant melanoma in the choroid of the left eye. Cystoscopy revealed black, nonpapillary tumors, suggesting metastatic malignant melanoma. Because no apparent invasive growth to muscle layer was observed by magnetic resonance imaging, transurethral resection was performed. Pathological appearance was compatible with metastatic malignant melanoma. No recurrence in urinary tract was observed; however, multiple liver metastasis was diagnosed at 3 months after surgery. Case 2: a 57-year-old Japanese man was diagnosed with right hydronephrosis due to ureteral tumor. He had a past history of subungual malignant melanoma to the left thumb 2 years prior to his visit. Right nephroureterectomy was performed, and pathological evaluation revealed metastatic malignant melanoma. He revisited 2 years later due to dysuria, and a large bladder tumor was revealed by ultrasound. Cystoscopy showed black-colored nonpapillary tumor, suggesting malignant melanoma. Total cystectomy was recommended; however, the patient withheld consent. Therefore, we performed transurethral resection. The resulting pathological finding was compatible with metastatic malignant melanoma without invasion to muscle layer. He remained free from local recurrence and metastasis for 22 years after surgery., Conclusion: We successfully performed metastasectomy for bladder and ureteral metastases without recurrence in the urinary tract. Long recurrence-free survival was observed in case 2. Complete resection for metastasis of malignant melanoma may have the potential to improve survival., (© 2024. The Author(s).)

Background: It is controversial whether the use of a double-J stent (DJ) in patients with bladder cancer before radical cystectomy (RC) increases the risk of tumour seeding in the upper tract and thus the risk of metachronous upper tract urothelial carcinoma (UTUC). The aim of our study is to investigate the risk of upper tract recurrence after RC in patients previously managed with a DJ stent., Methods: A total of 699 patients who had undergone RC between January 2003 and March 2022 with complete perioperative data and pathological outcome were included in our study. Patients treated preoperatively with a DJ stent were identified and compared for development of metachronous UTUC with those who did not receive prior internal stenting. Multivariable Cox regression analysis was used to determine predictors of UTUC occurrence among the possible pathological features; risk factors for mortality after RC were also examined., Results: Of 699 patients, 117 (16.7%) were managed preoperatively with a DJ stent. The overall probability of metachronous UTUC was 1%, 4% and 6% at 1, 3 and 5 years, respectively. The groups with and without DJ stenting were comparable regarding their clinicopathologic features, except for the higher incidence of hydronephrosis in the DJ group. At similar follow-up periods (median follow-up 32 months), metachronous UTUC was detected in four (3.4%) patients in the DJ group and in 13 (2.2%) in the non-stented group (P=0.44). The median interval (IQR) from cystectomy to UTUC was 40.5 (20-49) months in the DJ group and 37 (24-82) in the non-stented group (P=0.7). In the multivariable analysis, only presence of CIS (HR 3.83, 95% CI 1.19-12.29, P=0.024) and positive ureteral margin (HR=5.2, 95% CI 1.38-19.57, P=0.015) were predictors of metachronous UTUC. The study is limited by the retrospective nature and relatively short follow-up., Conclusions: Ureteral stenting for management of hydronephrosis in patients with bladder cancer undergoing RC is a viable option, without higher risk for UTUC or mortality. Patients with positive ureteral margin and CIS are considered high-risk groups for upper tract recurrence and should receive long-term, rigorous follow-up.

Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it's necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes., (© 2024. The Author(s).)

Introduction: Endoscopic tumor ablation of upper tract urothelial carcinoma (UTUC) allows for tumor control with the benefit of renal preservation but is impacted by intraoperative visibility. We sought to develop a computer vision model for real-time, automated segmentation of UTUC tumors to augment visualization during treatment. Materials and Methods: We collected 20 videos of endoscopic treatment of UTUC from two institutions. Frames from each video ( N  = 3387) were extracted and manually annotated to identify tumors and areas of ablated tumor. Three established computer vision models (U-Net, U-Net++, and UNext) were trained using these annotated frames and compared. Eighty percent of the data was used to train the models while 10% was used for both validation and testing. We evaluated the highest performing model for tumor and ablated tissue segmentation using a pixel-based analysis. The model and a video overlay depicting tumor segmentation were further evaluated intraoperatively. Results: All 20 videos (mean 36 ± 58 seconds) demonstrated tumor identification and 12 depicted areas of ablated tumor. The U-Net model demonstrated the best performance for segmentation of both tumors (area under the receiver operating curve [AUC-ROC] of 0.96) and areas of ablated tumor (AUC-ROC of 0.90). In addition, we implemented a working system to process real-time video feeds and overlay model predictions intraoperatively. The model was able to annotate new videos at 15 frames per second. Conclusions: Computer vision models demonstrate excellent real-time performance for automated upper tract urothelial tumor segmentation during ureteroscopy.

Background: Unmarried status has been associated with higher proportions of locally advanced stage and lower treatment dose intensification rates in several urological and non-urological malignancies. However, no previous investigators focused on the association between unmarried status and advanced stage (T 3-4 N 0-2 ) at presentation and lower nephroureterectomy (RNU) and systemic therapy (ST) rates in non-metastatic upper tract urothelial carcinoma (UTUC) patients., Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, all non-metastatic UTUC patients were identified. Multivariable logistic regression models (LRMs) tested for differences in stage at presentation and treatment (RNU and ST) according to marital status (married vs unmarried), in a sex-specific fashion., Results: Of all 8544 non-metastatic UTUC patients, 4748 (56%) were male vs 3190 (44%) were female. Of all 4748 male UTUC patients, 1191 (25%) were unmarried. Of all 3190 female UTUC patients, 1608 (50%) were unmarried. In multivariable LRMs predicting RNU, unmarried status was an independent predictor of lower RNU rates in male (Odds Ratio [OR]: 0.56; P < .001), but not in female (OR: 0.81; P = .1) non-metastatic UTUC patients. In multivariable LRMs predicting ST exposure, unmarried status was an independent predictor of lower ST rates in both male (OR:0.73; P = .03) and female (OR:0.64; P < .001) UTUC patients. In multivariable LRMs predicting locally advanced stage (T 3-4 N 0-2 ), unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male (OR: 0.95; P = .5) or female (OR: 0.99; P = .9) UTUC patients., Conclusions: Unmarried male UTUC patients appear at risk of less being able to access RNU, relative to their married counterparts. Moreover, unmarried UTUC patients appear to less benefit from ST, regardless of sex. Conversely, unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male or female UTUC patients., Competing Interests: Disclosure Shahrokh F. Shariat: Horonraria: Astellas, Astra Zeneca, Bayer, BMS, Cepheid, Ferring, lpsen, Janssen, Lilly, MSD, Olympus, Pfizer, Pierre Fabre, Richard Wolf, Roche, Sanochemia, Sanofi, Takeda, Urogen. Consulting or Advisory Role: Astellas, Astra Zeneca, Bayer, BMS, Cepheid, Ferring, lpsen, Janssen, Lilly, MSD, Olympus, Pfizer, Pierre Fabre, Richard Wolf, Roche, Sanochemia, Sanofi, Takeda, Urogen. Speakers’ Bureau: Astellas, Astra Zeneca, Bayer, BMS, Cepheid, Ferring, lpsen, Janssen, Lilly, MSD, Olympus, Pfizer, Pierre Fabre, Richard Wolf, Roche, Sanochemia, Sanofi, Takeda, Urogen, Movember Foundation. Patents: Method to determine prognosis after therapy for prostate cancer - granted 2002-09-06, Methods to determine prognosis after therapy for bladder cancer - granted 2003-06-19, Prognostic methods for patients with prostatic disease - granted 2004-08-05; Soluble Fas urinary marker for the detection of bladder transitional cell carcinoma - granted 2010-07-20. Our research was conducted without any other potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Tumour recurrences are frequent among patients with upper tract urothelial carcinoma (UTUC) treated with ureteroscopy (URS). Therefore, guidelines recommend a strict follow-up regimen, but there is little evidence on how to do this., Objective: To analyse outcomes during our follow-up regimen and the impact on treatment in terms of ipsilateral UTUC recurrence, treatment conversion, and tumour upgrading, and to evaluate potential prognostic factors, including second-look URS outcomes. A secondary objective was to evaluate survival outcomes., Design, Setting, and Participants: The single-centre cohort included all adult patients with nonmetastatic UTUC treated with URS from January 2010 to December 2020. Follow-up involved endoscopy at 3-mo intervals in the first year, then at 6-mo intervals up to year 3, and yearly thereafter., Outcome Measurements and Statistical Analysis: Descriptive analyses were performed for the follow-up outcomes. The Andersen-Gill model for recurrent event analysis was used to analyse tumour recurrences, and multivariable Cox regression to analyse for predictors for treatment conversion in low-grade tumours., Results and Limitations: We analysed 71 patients with median follow-up of 49.5 mo. The overall 2-yr recurrence-free survival (RFS) rate was 22%. In low-grade disease, the 1-yr RFS rate was 50% and the 2-yr RFS rate was 29%. Treatment was converted to radical nephroureterectomy for 23 patients, at a median time to conversion of 9.9 mo. Upgrading was seen in 13 patients, at a median time to upgrading of 21.9 mo. No factors were prognostic for either tumour recurrence or treatment conversion. The 5-yr OS, CSS, and MFS rates were 82%, 86%, and 84%, respectively., Conclusions: Our data show that it is rational to extend endoscopic follow-up for UTUC treated with URS, as clinically relevant events (treatment conversion and tumour upgrading) occur beyond the current 6-mo guideline recommendation. Second-look URS outcomes were not prognostic for tumour recurrence or treatment conversion during follow-up., Patient Summary: Our study results show that for patients with cancer of the upper urinary tract treated with kidney-sparing surgery through a small telescope called a ureteroscope (URS), most of the clinically relevant events (treatment conversion and tumour upgrading) occur outside the current recommended follow-up of 6 months. Therefore, URS follow-up should be extended for these patients., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To compare the diagnostic performance of photodynamic diagnosis (PDD) enhanced with oral 5-aminolaevulinic acid between the suspected upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) cases., Methods: This retrospective study included 18 patients with suspected UTUC who underwent ureteroscopy (URS) with oral 5-ALA in the PDD-URS cohort between June 2018 and January 2019; and 110 patients with suspected BUC who underwent transurethral resection of bladder tumour (TURBT) in the PDD-TURBT cohort between January 2019 and March 2023. Sixty-three and 708 biopsy samples were collected during diagnostic URS and TURBT, respectively. The diagnostic accuracy of white light (WL) and PDD in the two cohorts was evaluated, and false PDD-positive samples were pathologically re-evaluated., Results: The area under the receiver operating characteristic curve (AUC) of PDD was significantly superior to that of WL in both cohorts. The per biopsy sensitivity, specificity, and positive and negative predictive values of PDD in patients in the PDD-URS and PDD-TURBT cohorts were 91.2 vs. 71.4, 75.9 vs. 75.3, 81.6 vs. 66.3, and 88.0 vs. 79.4%, respectively. The PDD-URS cohort exhibited a higher AUC than did the PDD-TURBT cohort (0.84 vs. 0.73). Seven of four false PDD-positive samples (57.1%) in the PDD-URS cohort showed potential precancerous findings compared with eight of 101 (7.9%) in the PDD-TURBT cohort., Conclusion: The diagnostic performance of PDD in the PDD-URS cohort was at least equivalent to that in the PDD-TURBT cohort., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Primary ureteral neoplasms are extremely rare in dogs, and ureteral involvement usually occurs owing to the invasion of renal and bladder tumors., Case Description: This case report describes a 12-year-old intact male mixed-breed dog referred to a private clinic with a six-month history of abdominal distention. A physical examination revealed mild abdominal pain. Hematological tests detected normocytic-normochromic anemia (hematocrit 33.6% [reference interval-RI: 37%-55%], red blood cells 4.93 M/µl [RI: 5.5-8.5 M/µl], and hemoglobin 12.4 g/dl [RI: 12-18.0 g/dl]). The results from the leukogram, thrombogram, renal, and hepatic panels were within the reference intervals for dogs. Abdominal ultrasonography revealed a cavitary mass measuring approximately 12 cm in diameter as the largest tumor in the left abdominal region over the left hepatic lobe or mesenteric site. Chest radiography did not reveal any metastasis. Therefore, the patient underwent exploratory laparotomy, during which the left ureter was found to be affected by a 12-cm mass that adhered to the left kidney. A unilateral left ureteronephrectomy was performed, and histology and immunohistochemistry (IHC) confirmed well-differentiated primary ureteral leiomyosarcoma. The patient survived for 130 days but died of lung metastasis., Conclusion: Ureteral leiomyosarcoma should be investigated and included in the list of differential diagnoses for primary ureteral neoplasms. Regardless of the therapeutic modality, the prognosis of ureteral leiomyosarcoma may be unfavorable, as shown in this report., Competing Interests: The authors declare no conflicts of interest.

Purpose: 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., Materials and Methods: 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., Results: 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., Conclusion: 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.

Purpose: The aim of this retrospective study was to evaluate the efficacy of adjuvant cisplatin-based chemotherapy in patients with locally advanced upper tract urothelial carcinoma (UTUC), administered following radical nephroureterectomy., Materials and Methods: Patients with UTUC, arising from renal pelvis or ureter, staged pT3/T4 or N+ were treated with adjuvant chemotherapy following surgery. The chemotherapy consisted of gemcitabine 1,000 mg/m2 on days 1 and 8, cisplatin 70 mg/m2 on day 1. Treatment was repeated every 3 weeks for up to 4 cycles. Endpoints included disease-free survival (DFS), metastasis-free survival (MFS), and safety., Results: Among 89 eligible patients, 85 (95.5%) completed at least 3 cycles of adjuvant chemotherapy. Chemotherapy was well tolerated, the main toxicities being mild-to-moderate gastrointestinal toxic effects and pruritus. With a median follow-up of 37 months, median DFS was 30 months (95% confidence interval, 22 to 39), and the median MFS was not reached. The 3-year DFS and MFS were 44% and 56%, respectively. Multivariate analyses revealed that the main factor associated with DFS and MFS was the lymph node involvement, whereas age, T category, grade, or the primary site of UTUC were not significantly associated with DFS or MFS., Conclusion: Adjuvant cisplatin-based chemotherapy after radical surgery of pT3/T4 or N+ UTUC was feasible and may demonstrate benefits in DFS and MFS. Whether novel agents added to the chemotherapy regimen, as a concurrent combination or maintenance, impacts on survival or reduces the development of metastases remains to be studied.

Background: This study aims to describe a rare case of primary ureteral hemangiosarcoma, in which surgical intervention preserved the kidney and ureter after tumor removal., Case Presentation: A 13-year-old, neutered male dog, weighing 14 kg, mixed-breed, presented with apathy, anorexia, acute-onset vomiting, and abdominal discomfort during the physical examination. Ultrasonography and pyelography revealed a right-sided dilation of the renal pelvis and ureter due to complete obstruction in the middle third of the ureter. A mass obstructing the lumen of the right ureter was completely resected, and ureteral suturing was performed, preserving the integrity of the involved structures. Histopathology confirmed primary ureteral hemangiosarcoma. Due to the local and non-invasive nature of the mass, chemotherapy was not initiated. The patient's survival was approximately two years, and normal renal function was preserved throughout this period., Conclusions: Considering this type of tumor in the differential diagnosis of upper urinary tract obstructive disorders. Furthermore, the preservation of the ureter and kidney is a suitable therapeutic option after surgical resection of non-invasive tumors., (© 2024. The Author(s).)

Objective: Disease recurrence, particularly intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), is common. We investigated whether violations of onco-surgical principles before or during RNU, collectively referred to as surgical violation (SV), were associated with survival outcomes.  Material and methods: Data from a consecutive series of patients who underwent RNU for UTUC 2001-2012 at Skåne University Hospital Lund/Malmö were collected. Preoperative insertion of a nephrostomy tube, opening the urinary tract during surgery or refraining from excising the distal ureter were considered as SVs. Survival outcomes in patients with and without SV (IVR-free [IVRFS], disease-specific [DSS] and overall survival [OS]) were assessed using multivariate Cox regression analyses (adjusted for tumour stage group, prior or concomitant bladder cancer, comorbidity and preoperative urinary cytology)., Results: Of 150 patients, 47 (31%) were subjected to at least one SV. Overall, SV was not associated with IVRFS (HR 0.81, 95% CI 0.4-1.6) but with worse DSS (HR 1.9, 95% CI 1.03-3.7) and OS (HR 1.9, 95% CI 1.2-3) in multivariable analysis. Additional analyses with a broader definition of SV including also preoperative instrumentation of the upper urinary tract (ureteroscopy and/or double J stenting) showed similar outcomes for DSS (HR 2.1, 95% CI 1.1-4.3)., Conclusion: Worse survival outcomes, despite no difference in IVR, for patients that were subjected to the violation of sound onco-surgical principles before or during RNU for UTUC strengthen the notion that adhering to such principles is a cornerstone in upper tract urothelial cancer surgery.

Purpose: We initiated a biomarker-informed preoperative study of infigratinib, a fibroblast growth factor receptor (FGFR) inhibitor, in patients with localized upper tract urothelial carcinoma (UTUC), a population with high unmet needs and tumor with a high frequency of FGFR3 alterations., Materials and Methods: Patients with localized UTUC undergoing ureteroscopy or nephroureterectomy/ureterectomy were enrolled on a phase 1b trial (NCT04228042). Once-daily infigratinib 125 mg by mouth × 21 days (28-day cycle) was given for 2 cycles. Tolerability was monitored by Bayesian design and predefined stopping boundaries. The primary endpoint was tolerability, and the secondary endpoint was objective response based on tumor mapping, done after endoscopic biopsy and post-trial surgery. Total planned enrollment: 20 patients. Targeted sequencing performed using a NovaSeq 6000 solid tumor panel., Results: From May 2021 to November 2022, 14 patients were enrolled, at which point the trial was closed due to termination of all infigratinib oncology trials. Two patients (14.3%) had treatment-terminating toxicities, well below the stopping threshold. Responses occurred in 6 (66.7%) of 9 patients with FGFR3 alterations. Responders had median tumor size reduction of 67%, with 3 of 5 patients initially planned for nephroureterectomy/ureterectomy converted to ureteroscopy. Median follow-up in responders was 24.7 months (14.9-28.9)., Conclusions: In this first trial of targeted therapy for localized UTUC, FGFR inhibition was well tolerated and had significant activity in FGFR3 altered tumors. Renal preservation was enabled in a substantial proportion of participants. These data support the design of a biomarker-driven phase 2 trial of FGFR3 inhibition in this population with significant unmet clinical needs.

Aim: This study aimed to report initial results of hypofractionated carbon-ion radiotherapy (C-ion RT) for inoperable upper tract ureteral cancer., Methods: Retrospective chart review was performed for five consecutive patients with medically inoperable ureter cancer that was treated with radical C-ion RT between December 2013 and December 2014. The median age of the patients was 80 years (range, 68-84 years). The reasons for inoperability were advanced age, post-contralateral nephrectomy, alcoholic cirrhosis, both advanced age and contralateral renal function degeneracy, and pneumonia. The median size of tumor was 2.8 cm (range, 2.2-4.0 cm). Diagnostic imaging did not identify lymph node metastases or distant metastases in any case. All patients underwent C-ion RT (52.8 Gy relative biological effectiveness; 12 fractions in 3 weeks). The clinical target volume encompassed the growth tumor volume with a 5-mm margin bilaterally; there was a 40-mm margin craniocaudally but the clinical target volume did not encompass the whole ureter., Results: Within a median follow-up time of 32.9 months (range, 24-36 months), two patients died and three remained alive. Neither local recurrence nor regional lymph node metastases were observed. Secondary bladder tumor was observed in four patients, and one patient had a liver metastasis. Grade 1 hematuria was observed in two patients, and Grade 3 pyelonephritis was observed in one patient as acute toxicity. Ureteral obstruction was observed in two patients., Conclusion: C-ion RT might be a useful treatment option for inoperable ureter cancer., (© 2023 The Authors. Asia‐Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Purpose: The study aimed to investigate the impact of adjuvant chemotherapy on time to recurrence (TTR) and overall survival (OS) in patients with histologic variants of upper tract urothelial carcinoma (VUTUC) following radical nephroureterectomy (RNU)., Materials and Methods: A retrospective review of 131 VUTUC patients' medical records, from a pool of 368 non-metastatic localized or locally advanced UTUC cases, treated at a single tertiary referral center between January 2011 and January 2021. The intervention was adjuvant chemotherapy administration post-RNU. TTR and OS were evaluated using Kaplan-Meier and Cox proportional hazard regression, covariates adjusted for age, postoperative GFR, history of neoadjuvant chemotherapy, T and N stage with stabilized inverse probability of treatment weighting (sIPTW)., Results: The application of adjuvant chemotherapy showed a significant extension in TTR (P = .01), but no substantial impact on OS (P = .19) after sIPTW adjustment for covariates. Multivariate analysis revealed adjuvant chemotherapy, tumor size, and lymphovascular invasion as significant prognostic factors for TTR. In contrast, only tumor size and perineural invasion were significant for OS. Adjuvant chemotherapy reduced the progression risk in certain VUTUC subtypes (squamous or glandular/micropapillary), but not in sarcomatoid variants., Conclusions: Adjuvant chemotherapy appears to improve TTR, albeit without a significant effect on OS, in nonmetastatic localized and locally advanced VUTUC patients post-RNU. While beneficial to some VUTUC subtypes, it did not yield significant advantages for sarcomatoid variants. Despite adjustments for known confounders, the study's findings may be subject to potential selection bias and unmeasured confounding factors., Competing Interests: Disclosure The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The role of kidney-sparing surgery in patients with high-risk upper urinary tract urothelial carcinoma is controversial. The present study aimed to assess oncological and functional outcomes of robot-assisted distal ureterectomy in patients with high-risk distal ureteral tumors., Methods: The ROBUUST 2.0 multicenter international (2015-2022) dataset was used for this retrospective cohort analysis. High-risk patients with distal ureteral tumors were divided based on type of surgery: robot-assisted distal ureterectomy or robot-assisted nephroureterectomy. A survival analysis was performed for local recurrence-free survival, distant metastasis-free survival, and overall survival. After adjusting for clinical features of the high-risk prognostic group, Cox proportional hazard model was plotted to evaluate significant predictors of time-to-event outcomes., Results: Overall, 477 patients were retrieved, of which 58 received robot-assisted distal ureterectomy and 419 robot-assisted nephroureterectomy, respectively, with a mean (±SD) follow-up of 29.6 months (±2.6). The two groups were comparable in terms of baseline features. At survival analysis, no significant difference was observed in terms of recurrence-free survival (P=0.6), metastasis-free survival (P=0.5) and overall survival (P=0.7) between robot-assisted distal ureterectomy and robot-assisted nephroureterectomy. At Cox regression analysis, type of surgery was never a significant predictor of worse oncological outcomes. At last follow-up patients undergoing robot-assisted distal ureterectomy had significantly better postoperative renal function., Conclusions: Comparable outcomes in terms of recurrence-free survival, metastasis-free survival, and overall survival between robot-assisted distal ureterectomy and robot-assisted nephroureterectomy patients, and better postoperative renal function preservation in the former group were observed. Kidney-sparing surgery should be considered as a potential option for selected patients with high-risk distal ureteral UTUC.

Myxoid pseudotumor is a pseudoneoplastic fibroblastic proliferation that has been described in the perinephric and renal sinus fat tissue. It is characterized by the presence of a myxoid matrix, intermingled with the adipocytes, and a hypocellular population of spindle-shaped and stellate cells. We report a myxoid pseudotumor involving the distal ureter, which broadens the spectrum of possible localizations of this lesion around the urinary tract. It occurred in an 80-year-old patient who underwent a nephroureterectomy indicated after an incidental radiological finding of a thickening of the distal left ureter wall which suggested a ureteral neoplasm. He had two voided urine and one ureteroscopic sample cytologies diagnosed as high-grade urothelial carcinoma, as well as a retrograde ureteroscopy ureteral biopsy which was diagnosed as urothelial carcinoma in situ. This emphasizes the problem of the possible misdiagnosis of myxoid pseudotumor as a ureteral infiltrative carcinoma due to the radiological findings being badly interpreted, compounded by the preoperative cytohistologic data on malignancy. A diffuse urothelial carcinoma in situ was seen in our specimen without infiltrative or papillary tumors. This would not support an obstructive pathogenetic mechanism as has been hypothesized for myxoid pseudotumor., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: It is unknown whether the stage of the primary may influence the survival (OS) of metastatic upper tract urothelial carcinoma (mUTUC) patients treated with nephroureterectomy (NU) and systemic therapy (ST). We tested this hypothesis within a large-scale North American cohort., Methods: Within Surveillance Epidemiology and End Results database 2000-2020, all mUTUC patients treated with ST+NU or with ST alone were identified. Kaplan-Maier plots depicted OS. Multivariable Cox regression (MCR) models tested for differences between ST+NU and ST alone predicting overall mortality (OM). All analyses were performed in localized (T1-T2) and then repeated in locally advanced (T3-T4) patients., Results: Of all 728 mUTUC patients, 187 (26%) harbored T1-T2 vs 541 (74%) harbored T3-T4. In T1-T2 patients, the median OS was 20 months in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU independently predicted lower OM (HR 0.37, p < 0.001). Conversely, in T3-T4 patients, the median OS was 12 in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU was not independently associated with lower OM (HR 0.85, p = 0.1)., Conclusions: In mUTUC patients, treated with ST, NU drastically improved survival in T1-T2 patients, even after strict methodological adjustments (multivariable and landmark analyses). However, this survival benefit did not apply to patients with locally more advanced disease (T3-T4)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Localized Upper Urinary Tract Urothelial Carcinoma (UTUC) is an uncommon cancer typically detected at an advanced stage. Currently, radical nephroureterectomy (RNU) with bladder cuff excision is the standard treatment for high-risk UTUC. This meta-analysis aims to evaluate the 5-year overall and cancer-specific survival and bladder recurrence rates in studies comparing endoscopic kidney-sparing surgeries (E-KSS) with RNU in localized UTUC., Evidence Acquisition: We performed a literature search on 20th April 2023 through PubMed, Web of Science, and Scopus. The PICOS model was used for study inclusion: P: adult patients with localized UTUC; I: E-KSS. C: RNU; O: primary: overall survival (OS); secondary: cancer-specific survival (CSS), bladder recurrence rate, and metastasis-free survival (MFS). S: retrospective, prospective, and randomized studies., Evidence Synthesis: Overall, 11 studies involving 2284 patients were eligible for this meta-analysis, 737 in the E-KSS group and 1547 in the RNU group. E-KSS showed a similar overall 5-year OS between E-KSS and RNU, and for low-grade tumors, while 5-year OS favored RNU for high-grade tumors (RR 1.84, 95% CI 1.26-2.69, p = 0.002). No difference emerged for 5-year CSS between the two groups, even when the results were stratified for low- and high grade tumors. Bladder recurrence rate and 5-year MFS were also similar between the two groups., Conclusions: Our review showed that E-KSS is a viable option for patients with localized UTUC with non-inferior oncological outcomes as compared with RNU, except for 5-year OS in high-grade tumors which favoured RNU., (© 2024. The Author(s).)

Background: It is unknown whether regional differences in patient, tumor, and treatment characteristics of upper tract urothelial carcinoma (UTUC) patients exist and may potentially result in regional overall mortality (OM) differences. We tested for inter-regional differences, according to Surveillance, Epidemiology, and End Results (SEER) registries., Methods: Using SEER database 2000 to 2016, patient (age, sex, race/ethnicity), tumor (location, grade) and treatment (nephroureterectomy, systemic therapy [ST]) characteristics of UTUC patients of all-stages were tabulated and graphically depicted in a stage-specific fashion (T 1-2 N 0 M 0 vs. T 3-4 N 0 M 0 vs. T any N 1-2 M 0 /T any N any M 1 ). Multivariable Cox regression (MCR) models tested for inter-regional differences in OM., Results: Regarding T 1-2 N 0 M 0 patients, statistically significant differences existed for race/ethnicity (Caucasian 71 vs. 98%), location (renal pelvis: 55 vs. 67%), grade (high 60 vs. 83%) and ST (5.5 vs. 13.9%). In MCR models, registries 3 (Hazard ratio [HR]:1.39; P < 0.001) and 4 (HR:1.31; P = 0.01) independently predicted higher OM and Registry 8 (HR:0.64; P = 0.001) lower OM. Regarding T 3-4 N 0 M 0 patients, statistically significant differences existed for race/ethnicity (Caucasian 70 vs. 98%), location (renal pelvis: 67 vs. 76%), grade (high 84 vs. 94%) and ST (18.7 vs. 29.5%). In MCR models, registries 3 (HR:1.42; P < 0.001) and 4 (HR:1.31; P = 0.009) independently predicted higher OM. Regarding T any N 1-2 M 0 /T any N any M 1 patients, statistically significant differences existed for location (renal pelvis: 63 vs. 82%), grade (high 92 vs. 98%) and ST (53.4 vs. 58.8%). In MCR models, Registry 3 (HR:1.37; P = 0.004) independently predicted higher OM and Registry 2, (HR:0.78; P = 0.02) lower OM., Conclusions: Inter-regional differences were recorded in patients, tumor, and treatment characteristics. Even after adjustment for these characteristics, OM differences persisted which may be indicative of regional differences in quality of care or expertise in UTUC management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. POUT was a phase III, randomized, open-label trial, including 261 patients with muscle-invasive or lymph node-positive, nonmetastatic upper tract urothelial cancer (UTUC) randomly assigned after radical nephroureterectomy to platinum-based chemotherapy (132) or surveillance (129). Primary outcome analysis demonstrated that chemotherapy improved disease-free survival (DFS). At that time, the planned secondary outcome analysis of overall survival (OS) was immature. By February 2022, 50 and 67 DFS events had occurred in the chemotherapy and surveillance groups, respectively, at a median follow-up of 65 months. The 5-year DFS was 62% versus 45%, univariable hazard ratio (HR), 0.55 (95% CI, 0.38 to 0.80, P = .001). The restricted mean survival time (RMST) was 18 months longer (95% CI, 6 to 30) in the chemotherapy arm. There were 46 and 60 deaths in the chemotherapy and control arms, respectively. The 5-year OS was 66% versus 57%, with univariable HR, 0.68 (95% CI, 0.46 to 1.00, P = .049) and RMST difference 11 months (95% CI, 1 to 21). Treatment effects were consistent across chemotherapy regimens (carboplatin or cisplatin) and disease stage. Toxicities were similar to those previously reported, and there were no clinically relevant differences in quality of life between arms. In summary, although OS was not the primary outcome measure, the updated results add further support for the use of adjuvant chemotherapy in patients with UTUC, suggesting long-term benefits.

Background: Bone metastasis (BM) carries a poor prognosis for patients with upper-tract urothelial carcinoma (UTUC). This study aims to identify survival predictors and develop a prognostic nomogram for overall survival (OS) in UTUC patients with BM., Methods: The Surveillance, Epidemiology, and End Results database was used to select patients with UTUC between 2010 and 2019. The chi-square test was used to assess the baseline differences between the groups. Kaplan-Meier analysis was employed to assess OS. Univariate and multivariate analyses were conducted to identify prognostic factors for nomogram establishment. An independent cohort was used for external validation of the nomogram. The discrimination and calibration of the nomogram were evaluated using concordance index (C-index), area under receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). All statistical analyses were performed using SPSS 23.0 and R software 4.2.2., Results: The mean OS for UTUC patients with BM was 10 months (95% CI: 8.17 to 11.84), with 6-month OS, 1-year OS, and 3-year OS rates of 41%, 21%, and 3%, respectively. Multi-organ metastases (HR = 2.21, 95% CI: 1.66 to 2.95, P < 0.001), surgery (HR = 0.72, 95% CI: 0.56 to 0.91, P = 0.007), and chemotherapy (HR = 0.37, 95% CI: 0.3 to 0.46, P < 0.001) were identified as independent prognostic factors. The C-index was 0.725 for the training cohort and 0.854 for the validation cohort, and all AUC values were > 0.679. The calibration curve and DCA curve showed the accuracy and practicality of the nomogram., Conclusions: The OS of UTUC patients with BM was poor. Multi-organ metastases was a risk factor for OS, while surgery and chemotherapy were protective factors. Our nomogram was developed and validated to assist clinicians in evaluating the OS of UTUC patients with BM., (© 2024. The Author(s).)