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Introduction: There is an ongoing need to identify various pathological factors that can predict various survival parameters in patients with upper tract urothelial carcinoma (UTUC). With this review, we aim to scrutinize the impact of several pathological factors on recurrence free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) in patients with UTUC. Materials and Methods: Systematic electronic literature search of various databases was conducted for this review. Studies providing multivariate hazard ratios (HR) for various pathological factors such as tumor margin, necrosis, stage, grade, location, architecture, lymph node status, lymphovascular invasion (LVI), carcinoma in situ (CIS), multifocality and variant histology as predictor of survival parameters were included and pooled analysis of HR was performed. Results: In this review, 63 studies with 35.714 patients were included. For RFS, all except tumor location (HR 0.94, p=0.60) and necrosis (HR 1.00, p=0.98) were associated with worst survival. All the pathological variables except tumor location (HR 0.95, p=0.66) were associated with worst CSS. For OS, only presence of CIS (HR 1.03, p=0.73) and tumor location (HR 1.05, p=0.74) were not predictor of survival. Conclusions: We noted tumor grade, stage, presence of LVI, lymph node metastasis, hydronephrosis, variant histology, sessile architecture, margin positivity and multifocality were associated with poor RFS, CSS and OS. Presence of CIS was associated with poor RFS and CSS but not OS. Tumor necrosis was associated with worst CSS and OS but not RFS. Tumor location was not a predictor of any of the survival parameters.

Background: Pathological stage and grade of renal pelvis urothelial carcinoma (RPUC) are difficult to estimate before radical nephroureterectomy (RNU). Objective: To examine tumor size as an independent predictor of muscle-invasive and/or non–organ-confined rates of RPUC at RNU. Design, setting, and participants: Within the Surveillance, Epidemiology and End Results (SEER) database (2004–2016), we identified nonmetastatic RPUC at RNU. Outcome measurements and statistical analysis: First, we examined stage and grade distributions. Second, two separate univariable and subsequent multivariable logistic regression models (LRMs) were fitted to test the association between tumor size and the rate of (1) muscle-invasive or higher (pT2–4N0–2) and (2) non–organ-confined (pT3–4N0–2) RPUC at RNU. Results and limitations: Of 4657 patients, 3052 (65.5%) had pT2–4N0–2 and 2382 (51.2%) pT3–4N0–2 RPUC at RNU. The median tumor size was 3.7 cm (interquartile range 2.5–5.0). The high-grade RPUC rate ranged from 71.1% to 87.2% (p < 0.001) among SEER registries. Conversely, no differences were recorded for stage (p > 0.05) or tumor size (p = 0.1) across all registries. Rates of pT2–4N0–2 and pT3–4N0–2 RPUC increased with tumor size. Specifically, for tumor size intervals from 0.1–1.0 cm to 9.1–10.0 cm, the pT2–4N0–2 rate ranged from 45% to 83% and the pT3–4N0–2 rate ranged from 23% to 75%, respectively (both p < 0.001). In multivariable LRMs, tumor size (in 1-cm units) was an independent predictor of pT2–4N0–2 (odds ratio [OR] 1.25; p < 0.001) and pT3–4N0–2 (OR 1.30; p < 0.001) disease at RNU. Conclusions: Tumor size is a key predictor of muscle-invasive or non–organ-confined RPUC. Greater tumor size directly and virtually linearly predicts a higher rate of invasive or non–organ-confined RPUC at RNU. Patient summary: For patients with cancer in urinary tract cells lining the kidney, larger tumor size predicts worse stage of the disease at surgery.

Kidney-sparing procedures for upper tract urothelial carcinoma (UTUC) have evolved from imperative to elective indications for management of low-risk disease. Ureterorenoscopy is the most common procedure for the diagnosis, treatment, and surveillance of UTUC. A notable consideration following ureterorenoscopy is the higher risk of downstream bladder seeding. Here we review the importance of and scientific evidence for chemoprophylaxis after ureterorenoscopy. PATIENT SUMMARY: For patients with low-risk cancer of the upper urinary tract, a procedure called ureterorenoscopy (URS) involving insertion of a thin telescope through the ureter and into the kidney is increasingly used for biopsy. URS increases the risk of cancer seeding in the bladder. We review evidence on the benefit of prophylactic bladder chemotherapy after URS.

The incidence and risk factors for metachronous upper tract urothelial carcinoma (UTUC) following radical cystectomy (RC) remain incompletely defined, which has limited the ability to individualize postoperative surveillance.A retrospective review of 2 institutional registries was performed to identify patients undergoing RC for urothelial carcinoma. Multivariable Cox proportional hazard models for metachronous post-RC UTUC were developed in one institutional data set and validated in the second institutional data set. A post-RC UTUC risk score was then developed from these models.A total of 3,170 RC patients were included from the training cohort and 959 RC patients from the validation cohort. At a median followup after RC of 4.6 years (IQR 2.1-8.7), 167 patients were diagnosed with UTUC. On multivariable analysis in the training cohort, risk factors for metachronous UTUC were the presence of positive urothelial margin (HR 2.60, p0.01), history of bacillus Calmette-Guérin treatment prior to RC (HR 2.20, p0.01), carcinoma in situ at RC (HR 2.01, p0.01) and pre-RC hydronephrosis (HR 1.48, p=0.04). These factors had similar discriminative capacity in the training and validation cohorts (C-statistic 0.71 and 0.73, respectively). A UTUC risk score was developed with these variables which stratified patients into low (0 points), intermediate (1-3 points), and high risk (4+ points) for post-RC UTUC, with respective 5-year UTUC-free survivals of 99%, 96%, 89% in the training cohort and 98%, 96%, and 91% in the validation cohort.We developed and validated a risk score for post-RC UTUC that may optimize UTUC surveillance protocols after RC.

Purpose Urothelial carcinomas (UCs), also known as transitional cell carcinomas, account for the majority of upper urinary tract tumors. The gold-standard therapy for operable patients with localized disease is radical nephroureterectomy. However, some patients are not surgical candidates. Data on the use of modern radiation therapy for upper urinary tract UC (UTUC) are scarce. The purpose of this study was to assess the safety and efficacy of SABR in UTUC. Methods and Materials This retrospective study included all patients with UTUC treated with SABR at one institution. Charts were reviewed to evaluate renal function and the development of toxicity using Common Terminology Criteria for Adverse Events, version 3.0. Tumor response on follow-up imaging with computed tomography or magnetic resonance imaging scans was assessed using the Response Evaluation Criteria in Solid Tumors, version 1.1. Results A total of 16 patients (7 patients with UC at the ureter and 9 at the renal pelvis) were identified as treated with SABR. Of the 9 patients with renal pelvis UC, 4 had a previous history of bladder cancer. At the time of treatment, the median age was 85 years (range, 67-95 years). Most patients received 40 Gy in 8 fractions every second day. The median followup was 21 months (range, 3-110 months). Most patients maintained stable renal function, and only 2 patients developed worsening chronic kidney disease, but none required dialysis. Acutely, 4 patients developed grade 1 diarrhea, and 1 patient had new grade 1 hematuria. No chronic side effects were observed. One patient did not have follow-up imaging and was excluded from the tumor-response analysis. Two patients had a complete response of the treated lesion, 9 had a partial response, 2 had stable disease, and 2 had disease progression within the treatment field. Conclusions This small case series suggests that SABR for UTUC is safe and well-tolerated, with good radiographic tumor response to ablative doses of radiation therapy.

The prognosis of patients undergoing 2-sided radical nephroureterectomies (RNUs) with a residual bladder due to bilateral upper tract urothelial carcinoma (UTUC) is poorly understood. This study was aimed toward surveying the oncology outcomes and prognostic factors that may help in shared decision-making related to bladder preservation in patients preparing to receive 2-sided RNUs. Patients with synchronous or metachronous bilateral UTUC who received bilateral RNUs with a residual bladder in our hospital were retrospectively reviewed. Clinical and pathological data were analyzed for potential variables affecting the oncology outcomes. A total of 50 patients were included. The average age at completion of the 2-sided RNU was 62.7 ± 12.4 years, with a mean follow-up of 88.4 ± 59.3 months after the 2-sided RNUs. The medium overall survival was 13.4 ± 1.8 years. Twenty-six patients (52%) had cancer recurrence in the residual bladder, but only 2 (8%) of the recurrences were muscle invasive. The highest UTUC stage was the only predictive factor for cancer-specific survival (CSS) rather than intravesical recurrence. The 5 year CSS rates in patients with the highest UTUC stage ≦ pT2 and ≧ pT3 were 90% and 51%, respectively (p = 0.007). Risk of cancer recurrence in the residual bladder is high, but does not affect survival outcomes. The highest UTUC stage plays a significant role in cancer-specific survival. With a careful patient surveillance, bladder preservation may be reasonable in patients with bilateral UTUC preparing for 2-sided RNUs.

OBJECTIVES To investigate the significant predictors of contralateral upper tract recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. METHODS Between January 2001 and December 2015, 548 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy in a single institution were included in this retrospective cohort study. Several clinicopathological characteristics and outcomes were explored. The crucial end-point was the diagnosis of contralateral upper tract recurrence after radical nephroureterectomy. RESULTS Of the 548 patients, the median age was 68 years (range 24-93 years), and the median follow-up time after radical nephroureterectomy was 41 months (range 8-191 months). Contralateral upper tract recurrence occurred in 28 patients (5.1%). The median time period between radical nephroureterectomy and contralateral upper tract recurrence was 15.4 months (range 3.4-52.4 months). In the multivariate analysis, preoperative estimated glomerular filtration rate

The occurrence of ureteral metastasis from distant primary tumors is uncommon, and appears to be especially rare when it originates from the lungs. In the case presented here, a patient with lumbago and left hydronephrosis was diagnosed with left ureteral metastasis of pulmonary adenocarcinoma after a CT‐guided percutaneous transthoracic needle biopsy of the lung and retroperitoneal laparoscopic left nephroureterectomy. He accepted the targeted therapy because the lung tumor epidermal growth factor receptor mutation (exon19 deletion) was positive, and preoperative staging of lung adenocarcinoma was stage IVA. After an 8‐month follow‐up, he is still alive and well, with no local recurrence or distant metastases. The therapy outcome assessment is stable disease. Although rare, our case has demonstrated that pulmonary adenocarcinoma has the possibility of metastasizing to the ureter, a risk that should be considered in some lung cancer patients., A patient with lumbago and left hydronephrosis was diagnosed with left ureteral metastasis of pulmonary adenocarcinoma after a CT‐guided percutaneous transthoracic needle biopsy of the lung and retroperitoneal laparoscopic left nephroureterectomy. Although rare, our case has demonstrated that pulmonary adenocarcinoma has the possibility of metastasizing to the ureter, a risk that should be considered in some lung cancer patients.

Metastatic upper urinary tract urothelial carcinoma (mUTUC) is a relatively rare urothelial carcinoma, and little attention has been given to it. Our study established a nomogram by analyzing the prognostic factors of mUTUC to predict the survival of patients and revealed that the role of surgery at the primary tumor site. We extracted our data (2010–2016) from the Surveillance, Epidemiology, and End Results (SEER) database, and 628 patients with distant metastasis were identified. Propensity score matching (PSM) was used to balance the clinical variable bias in a 1:1 ratio. After PSM, we enrolled 502 patients in our study cohort. Univariate and multivariate Cox regression analyses and Kaplan–Meier curves showed that T stage, N stage, hepatic metastasis, surgery, and chemotherapy were prognostic factors for mUTUC before and after PSM. Based on the findings, a nomogram was constructed to predict the 12‐month survival of patients with distant metastasis. The analysis of subgroups of T stage, N stage, and different metastatic sites demonstrated that the survival of patients with T1/T2, N0/N1/N2/N3, metastasis including liver, and metastasis including bone could be improved by a combination of surgery and chemotherapy, while for the patients with T3/T4/TX, NX, metastasis including lung, and metastasis including distant lymph nodes, chemotherapy alone was a better choice to improve their overall survival. Radiotherapy has been proven to be useful for patients with N1/N2/N3 stage. We have provided more precise treatment strategies for stage IV patients. Our research fully affirms the role of surgery on primary site in UTUC patients with distant metastasis and the significance of classifying the patients into subgroups by integrating variables including T stage, N stage, and different metastatic sites to select the optimal treatment method., It is a research about prognostic factors of metastatic upper urinary tract urothelial carcinoma (mUTUC) including metastatic patterns, therapy modes, and T/N stage based on the data extracted from SEER database. It reveals that the role of surgery on primary site is significant in the treatment of metastatic upper urinary tract urothelial carcinoma.

BACKGROUND: Several groups have proposed features to identify low-risk patients who may benefit from endoscopic kidney-sparing surgery in upper tract urothelial carcinoma (UTUC). OBJECTIVE: To evaluate standard risk stratification features, develop an optimal model to identify ≥pT2/N+ stage at radical nephroureterectomy (RNU), and compare it with the existing unvalidated models. DESIGN, SETTING, AND PARTICIPANTS: This was a collaborative retrospective study that included 1214 patients who underwent ureterorenoscopy with biopsy followed by RNU for nonmetastatic UTUC between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed multiple imputation of chained equations for missing data and multivariable logistic regression analysis with a stepwise selection algorithm to create the optimal predictive model. The area under the curve and a decision curve analysis were used to compare the models. RESULTS AND LIMITATIONS: Overall, 659 (54.3%) and 555 (45.7%) patients had ≤pT1N0/Nx and ≥pT2/N+ disease, respectively. In the multivariable logistic regression analysis of our model, age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.0-1.03, p = 0.013), high-grade biopsy (OR 1.81, 95% CI 1.37-2.40, p

Objective: The aim of this study was to investigate whether diagnostic ureteroscopy (URS) biopsy is unfavourable for bladder tumour recurrence in upper urinary tract urothelial carcinoma (UTUC). Materials and Methods: We performed a retrospective analysis of 195 patients diagnosed with UTUC, who were divided into a diagnostic URS group (URS+) and a nondiagnostic URS group (URS–) according to whether diagnostic ureteroscopic biopsy was performed. A Cox regression model was used to analyse the risk factors for intravesical recurrence (IVR)-free survival (IRFS) and overall survival (OS) in UTUC after radical nephroureterectomy (RNU). Kaplan-Meier analysis was used to estimate the influence of factors on the incidence of IVR and the cumulative survival rate of UTUC. Results: Patients with a maximum tumour diameter of less than 3.1 cm, low-stage tumours, and ureteral tumours were more likely to undergo diagnostic URS before radical surgery. Multivariate Cox regression analysis showed that tumour pathological stage and diagnostic ureteroscopic biopsy can be used as predictors of IVR after RNU (p = 0.019, 0.033). Kaplan-Meier survival analysis found that diagnostic ureteroscopic biopsy was a high-risk factor for IRFS (p = 0.034). Subcomponent analysis showed that pTa/Tis/T1, pT2, pT3/pT4 stage, and diagnostic ureteroscopic biopsy with pTa/Tis/T1 stage were unfavourable for IVR (p = 0.047). Conclusion: Diagnostic ureteroscopic biopsy before RNU should be carefully selected for patients with atypical preoperative UTUC. We believe that intravesical chemotherapy drug perfusion can be used after surgery to prevent IVR if biopsy is unavoidable, but this still requires further prospective studies.

Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) has an incidence of approximately 20%-50%. Studies to date have been composed of mixed treatment cohorts-open, laparoscopic and robotic. The objective of this study is to assess clinicopathological risk factors for intravesical recurrence after RNU for UTUC in a completely minimally invasive cohort.We performed a multicenter, retrospective analysis of 485 patients with UTUC without prior or concurrent bladder cancer who underwent robotic or laparoscopic RNU. Patients were selected from an international cohort of 17 institutions across the United States, Europe and Asia. Univariate and multiple Cox regression models were used to identify risk factors for bladder recurrence.A total of 485 (396 robotic, 89 laparoscopic) patients were included in analysis. Overall, 110 (22.7%) of patients developed IVR. The average time to recurrence was 15.2 months (SD 15.5 months). Hypertension was a significant risk factor on multiple regression (HR 1.99, CI 1.06; 3.71, p=0.030). Diagnostic ureteroscopic biopsy incurred a 50% higher chance of developing IVR (HR 1.49, CI 1.00; 2.20, p=0.048). Treatment specific risk factors included positive surgical margins (HR 3.36, CI 1.36; 8.33, p=0.009) and transurethral resection for bladder cuff management (HR 2.73, CI 1.10; 6.76, p=0.031).IVR after minimally invasive RNU for UTUC is a relatively common event. Risk factors include a ureteroscopic biopsy, transurethral resection of the bladder cuff, and positive surgical margins. When possible, avoidance of transurethral resection of the bladder cuff and alternative strategies for obtaining biopsy tissue sample should be considered.

Purpose This study aimed to evaluate the effects of bladder cuff method on oncological outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma.Materials and Methods The records of 1,095 patients treated with RNU performed at our hospital between 1994 and 2018 were retrospectively reviewed; 856 patients with no bladder tumor history were enrolled in the present study. The management of bladder cuff was divided into two categories: extravesical ligation (EL) or transvesical resection (TR). Survival was analyzed using the Kaplan-Meier method and Cox regression analyses were performed to determine which factors were associated with intravesical recurrence (IVR)–free survival (IVRFS), cancer-specific survival (CSS), and overall survival (OS).Results The mean patient age was 64.8 years and the median follow-up was 37.7 months. Among the 865 patients, 477 (55.7%) underwent the TR and 379 (44.3%) the EL. Significantly higher IVRFS (p=0.001) and OS (p=0.013) were observed in the TR group. In multivariable analysis, IVR, CSS, and OS were independently associated with the EL. Among 379 patients treated with the EL, eight underwent remnant ureterectomy. Based on radical cystectomy–free survival, significant difference was not observed between the two groups. However, significantly higher IVRFS was observed in the TR group when the tumor was located in the renal pelvis.Conclusion Intramural complete excision of the distal ureter during RNU should be the gold standard approach compared with EL for the management of distal ureter in terms of oncological outcomes.

To analyze utilization and outcomes of cytoreductive surgery (CRS) after systemic chemotherapy in select patients with metastatic upper tract urothelial carcinoma (UTUC).We identified 1,73 patients with cM1 UTUC from the National Cancer Database who were treated with first-line multiagent chemotherapy from 2004 to 2015. Patients considered surgical candidates based on Charlon-Deyo performance score were stratified into nonsurgical versus surgical arms based on receipt of CRS after systemic therapy. Those receiving radiation, immunotherapy, or other types of treatment were excluded. Cox proportional hazard models were used to analyze prognostic factors for overall survival (OS). Propensity-score matching and inverse probability of treatment weighting-adjusted regression models were used to compare OS.A total of 1182 patients were included of which 349 (29.5%) were treated with definitive surgery. Median follow-up was 64 months (95% confidence interval:49.8-79.4) for chemotherapy+surgery versus 61.2 (52.2-78.7) for the chemotherapy-alone arms (P = .09). Patients treated with surgery were younger and more commonly treated at academic facilities. Patients who received CRS had improved median-OS versus those treated with chemotherapy alone (13.7 vs 10.8 months, log-rank P-value.001). Predictors of OS were performance score, treatment at academic facility, and performance of CRS. Furthermore, in propensity-score and inverse probability of treatment weighting-adjusted Cox regression analyses, CRS was associated with significant OS benefit (hazard ratios = 0.61, 95% confidence interval:0.49-0.77, and 0.63;0.55-0.72; respectively).We provide a contemporary report on the survival benefit of CRS after treatment with systemic therapy for M1 UTUC patients. Longitudinal studies are needed to evaluate the role of surgery, when feasible, within multidisciplinary approaches for this relatively, rare disease.

Background To describe the techniques and outcomes of complete transperitoneal laparoscopic nephroureterectomy (CTLNU) for upper urinary tract urothelial carcinoma (UTUC) in a single position. Materials and methods Those patients with localized UTUC were included, among which 50 cases had CTLNU while 48 cases had laparoscopic nephroureterectomy with open bladder cuff excision (LNOBE). The clinical data were collected and analyzed retrospectively. Results All 98 patients underwent successful procedures of radical nephroureterectomy without transferring into open surgery. No significant difference was found among baseline clinical characteristics. Compared with the LNOBE group, the CTLNU group had a shorter operative time (98.5±40.3 min vs. 132.4±60.2 min), less blood loss (60.4±20.3 ml vs. 150.6±50.2 ml), shorter length of hospital stay (5.3±2.2 days vs. 8.1±2.3 days), and shorter incision (6.3±1.2 cm vs. 11.5±3.2 cm). The disease-related outcomes such as pathological stage, tumor grade, and recurrence rate were similar between the two groups. Conclusions The CTLNU in a single position had advantages of shorter operation time, less blood loss, and shorter incision length. This surgical technique is a more minimally invasive, simplified, and effective way to perform the radical nephroureterectomy.

Purpose To investigate the safety and efficacy of ureteroscopic cryoablation by a liquid-nitrogen system in a porcine model and for patients with upper tract urothelial carcinoma (UTUC) of a solitary kidney. Methods In the animal experiment, the right-sided ureter was frozen in nine pigs. Eight were randomly assigned to two different groups according to the freezing duration of 60 or 90 s. The other one was designed to receive a 10-min freeze. The treated ureters were harvested at 30 min, 2 days, 4 weeks, and 3 months after cryoablation for histological evaluation. After the animal study, we conducted a pilot clinical trial that enrolled six patients who were diagnosed with UTUC of a solitary kidney and received therapeutic management with ureteroscopic cryoablation at our center. Perioperative adverse events and oncological outcomes were evaluated. Results In the porcine model, the liquid-nitrogen system was capable of forming a therapeutic ice ball which infiltrated the full-thickness ureter and induced apoptosis and necrosis from mucosa to lamina muscularis through histological examination. In the clinical trial, cryoablation was successfully performed under ureteroscopy in all the patients, without intraoperative ureteral perforation, avulsion, or active hemorrhage. No recurrence in situ was observed during a median follow-up period of 12.5 months. Hydronephrosis and ureteral stricture was observed in one patient and was managed with ureteroscopic balloon dilation. Conclusions Ureteroscopic cryoablation induced by liquid nitrogen is a promising technique for conservative management of UTUC with benefits of improving local tumor control and preservation of a solitary kidney.

Supplemental Digital Content is available in the text., Large cell neuroendocrine carcinoma (LCNEC) of the urinary tract is a rare disease. We present a relatively large retrospective cohort of urinary LCNEC, 20 from the urinary bladder, and 2 from the ureter, from a single institution. The patients included 16 men and 6 women with a median age of 74.5 years. Most LCNEC presented at an advanced stage with tumors invading the muscularis propria and beyond (21/22). Eight cases were pure LCNEC, while 14 cases were mixed with other histologic types, including conventional urothelial carcinoma (n=9), carcinoma in situ (n=7), small cell carcinoma (n=6), and urothelial carcinoma with glandular (n=3) features. Most LCNEC expressed neuroendocrine markers synaptophysin (22/22), chromogranin (13/16), CD56 (7/7), TTF1 (8/8), and INSM1 (2/3). They were negative for common urothelial markers including HMWCK (0/3), p40/p63 (0/6), CK20 (0/10), and had variable GATA3 staining (4/8). Ki-67 stained 25% to nearly 100% tumor cell nuclei. Patient survival was associated with cancer stage, and pure LCNEC showed worse survival than mixed LCNEC. Compared with small cell carcinoma at similar stages from a prior study, LCNEC had a worse prognosis only when patients developed metastatic disease. For organ-confined LCNEC, neoadjuvant chemotherapy followed by radical resection is the treatment option to achieve long-term survival.

The cornerstone for diagnosis and treatment of bladder and upper tract urothelial carcinoma involves surgery. Transurethral resection of bladder tumors forms the basis of further management. Radical cystectomy for invasive bladder carcinoma provides good oncologic outcomes. However, it can be a morbid procedure, and advances such as minimally invasive surgery and early recovery after surgery need to be incorporated into routine practice. Diagnostic ureteroscopy for upper tract carcinoma is needed in cases of doubt after cytology and imaging studies. Low-risk cancers can be managed with conservative endoscopic surgery without compromising oncological outcomes; however, high-risk disease necessitates radical nephroureterectomy.

Purpose Renal function is frequently impaired in the patients with upper tract urothelial carcinoma. We aimed to evaluate the impact of renal function and its change after surgery on survival rates in patients with upper tract urothelial carcinoma after nephroureterectomy. Methods The study cohort comprised 755 patients with upper tract urothelial carcinoma who underwent nephroureterectomy between 1995 and 2016 at nine hospitals in Japan. Estimated glomerular filtration rate was calculated using the three-variable Japanese equation for glomerular filtration rate estimation from serum creatinine level and age. Outcomes were recurrence-free, cancer-specific and overall survivals. Univariate and multivariate Cox proportional hazards regression analyses were used. Results Median patients’ age was 72 years old. Pre- and post-surgical median estimated glomerular filtration rate were 55.5 and 42.9 ml/min/1.73 m2, respectively. Median estimated glomerular filtration rate decline after surgery, which represents function of the affected side kidney, was 13.1 ml/min/1.73 m2. The 5-year recurrence-free, cancer-specific and overall survivals were 68.3, 79.4 and 74.0%, respectively. Multivariate analysis indicated that lower preoperative estimated glomerular filtration rate and estimated glomerular filtration rate decline were associated with poorer recurrence-free, cancer-specific and overall survivals, but post-operative estimated glomerular filtration rate was not. Estimated glomerular filtration rate decline was more significant poor-prognosticator than preoperative estimated glomerular filtration rate. Proportions of the patients with estimated glomerular filtration rate Conclusions Lower preoperative renal function, especially of the affected side kidney, was significantly associated with poor prognosis after nephroureterectomy for upper tract urothelial carcinoma. Many patients with locally advanced disease have reduced renal function at diagnosis and even more after surgery.

OBJECTIVE To examine the discrepancy between clinical and pathological T stages in patients with urothelial carcinoma of the upper urinary tract treated with radical surgery, and to compare them with the corresponding discrepancy in urothelial carcinoma of the bladder. METHODS We used the Hospital-Based Cancer Registry data in Japan to extract urothelial carcinoma of the bladder cases (n = 3747) and urothelial carcinoma of the upper urinary tract cases (n = 6831), including urothelial carcinoma of the renal pelvis (n = 3295) and urothelial carcinoma of the ureter (n = 3536) with cT1-4N0M0 diagnosed in 2012-2015, histologically confirmed, and treated with radical surgery without chemotherapy or radiotherapy. We compared the T-stage discrepancy among different tumor locations. RESULTS The proportions of overall T-stage discrepancy in the urothelial carcinoma of the renal pelvis (40.8%) and urothelial carcinoma of the ureter (42.9%) groups tended to be higher compared with that in the urothelial carcinoma of the bladder (38.8%) group. The upstaging rate from clinical non-muscle-invasive cancer (≤cT1) to pathological muscle-invasive cancer (≥pT2) was significantly higher in the urothelial carcinoma of the renal pelvis and urothelial carcinoma of the ureter groups compared with the urothelial carcinoma of the bladder group (P = 0.002, P

Purpose of review To assess patterns of presentation, diagnostics and treatment in patients with upper tract urothelial carcinoma (UTUC), a multicentre registry was launched. Clinical data of UTUC patients were prospectively collected over a 5-year period. Recent findings Data from 2380 patients were included from 2014 to 2019 (101 centres in 29 countries). Patients were predominantly male (70.5%) and 53.3% were past or present smokers. The majority of patients (58.1%) were evaluated because of symptoms, mainly macroscopic hematuria. Computed tomography (CT) was the most common performed imaging modality (90.5%). A ureteroscopy (URS) was part of the diagnostic process in 1184 (49.7%) patients and 488 (20.5%) patients were treated endoscopically. In total, 1430 patients (60.1%) were treated by a radical nephroureterectomy, 59% without a prior diagnostic URS. Eighty-two patients (3.4%) underwent a segmental resection, 19 patients (0.8%) were treated by a percutaneous tumour resection. Summary Our data is in line with the known epidemiologic characteristics of UTUC. CT imaging is the preferred imaging modality as also recommended by guidelines. Diagnostic URS gained a stronger position, however, in almost half of patients a definitive treatment decision was made without complete endoscopic information. Only one-third of patients with UTUC are currently treated with kidney sparing surgery.

Upper-tract urothelial cancer comprises only 3% of all urothelial cancers. Risk factors include tobacco smoking, recurrent urinary infection, urolithiasis and analgesic abuse. Urolithiasis-induced chronic inflammation leads to urothelial proliferation and eventual malignant transformation. The most common association is reported with squamous cell cancer. A 54-year man under evaluation for right flank pain was diagnosed with a large distal ureteric stone and urothelial cancer of the entire right ureter and renal pelvis. The patient underwent right nephroureterectomy and stone retrieval, with urinary bladder cuff excision and pelvic lymph node dissection. On follow-up, the patient succumbed to disease recurrence with widespread metastasis. Urothelial cancer associated with stone disease is atypical. Long-standing inflammation causing metaplastic and dysplastic changes is a possible hypothesis. Careful assessment of the malignancy should be looked for in patients with long-standing obstruction due to stone disease.

To evaluate stage at presentation and cancer-specific mortality (CSM) in upper urinary tract tumors according to histologic subtype.Within the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2016), we identified patients with upper urinary tract tumors with pure variant histology (UTVH) and pure upper urinary tract urothelial carcinoma (UTUC). Cumulative incidence plots, after propensity score matching for tumor and patient characteristics, addressed CSM. Subgroup analyses addressed efficacy of radical nephroureterectomy (RNU) in stage T1-2 and of chemotherapy in metastatic UTVH patients.Of all 11,809 upper urinary tract tumor patients, 154 (1.3%) harbored squamous cell carcinoma (SCC), 86 (0.7%) adenocarcinoma, 39 (0.3%) neuroendocrine carcinoma, 38 (0.3%) other UTVH, and 11,492 (97.3%) UTUC. UTVH patients were more likely to exhibit metastatic stage disease at diagnosis than UTUC (odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P .01). After detailed matching for performance status, only SCC showed significantly higher CSM than UTUC (multivariate HR = 1.71; P .01). Subgroup analyses in stage T1-2 RNU patients showed, relative to UTUC patients, no CSM differences for SCC or adenocarcinoma patients. No significant survival benefit for chemotherapy administration was identified in patients with metastatic SCC or metastatic adenocarcinoma. This study is limited by its sample size and the missing centralized pathologic review.Disease stage at diagnosis is more advanced in UTVH patients than UTUC. Across all stages, CSM is higher for SCC than for UTUC. However, in T1-2 stage disease, RNU results in similar survival in SCC or adenocarcinoma versus UTUC.

Background During the past two decades, laparoscopic radical nephroureterectomy (LRNU) has been proposed as an alternative technique to open radical nephroureterectomy (ORNU) and has become increasingly accepted for the treatment of patients with upper tract urothelial carcinoma (UTUC). Nevertheless, the oncologic efficacy of LRNU remains controversial, especially for the treatment of locally advanced (T3/T4 and/or N+) UTUC. In this meta-analysis, we aimed to cumulatively compare the oncological outcomes of LRNU versus ORNU. Materials and methods The present meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search was conducted of three electronic databases, namely, Medline, Embase, and Cochrane Library. Outcome measurements of cancer-specific survival (CSS), overall survival (OS), intravesical recurrence-free survival (IVRFS), and recurrence-free survival (RFS), including hazard ratios (HRs) and 95% confidence intervals (CIs), were extracted and pooled. Results Eighteen articles published from 2007 to 2020 were included in the final quantitative analysis. One study was a randomized controlled trial (RCT), and the remaining articles had a retrospective design. Among a total of 10,730 participants in the selected papers, 5959 (55.5%) and 4771 (44.5%) underwent ORNU and LRNU, respectively. The results of pooled analyses revealed no significant differences in CSS (HR 0.84, 95% CI 0.60–1.19, p = 0.33), OS (HR 0.84, 95% CI 0.62–1.13, p = 0.25), IVRFS (HR 1.08, 95% CI 0.85–1.39, p = 0.52), and RFS (HR 1.09, 95% CI 0.94–1.25, p = 0.26) between LRNU and ORNU groups. Furthermore, the results of subgroup analyses for pT3/T4 and pTany N+ populations did not confirm any statistically significant differences between LRNU and ORNU in terms of any survival parameter. Conclusions Our present meta-analysis of current evidence suggests that LRNU and ORNU have comparable oncological outcomes in patients with UTUC, even in those with locally advanced disease. Further multicenter RCTs with large sample sizes and uniform data regarding specific surgical procedures, such as bladder cuff excision, are required to establish definitive conclusions.

Background Simultaneous urothelial cancer manifestation in the lower and upper urinary tract affects approximately 2% of patients. Data on the surgical benchmarks and mid-term oncological outcomes of enbloc robot-assisted radical cystectomy and nephro-ureterectomy are scarce. Methods After written informed consent was obtained, we prospectively enrolled consecutive patients undergoing enbloc radical cystectomy and nephro-ureterectomy with robotic assistance from the DaVinci Si-HD® system in a prospective institutional database and collected surgical benchmarks and oncological outcomes. Furthermore, as one console surgeon conducted all the procedures, whereas the team providing bedside assistance was composed ad hoc, we assessed the impact of this approach on the operative duration. Results Nineteen patients (9 women), with a mean age of 73 (SD: 7.5) years, underwent simultaneous enbloc robot-assisted radical cystectomy and nephro-ureterectomy. There were no cases of conversion to open surgery. In the postoperative period, we registered 2 Clavien-Dindo class 2 complications (transfusions) and 1 Clavien-Dindo class 3b complication (port hernia). After a median follow-up of 23 months, there were 3 cases of mortality and 1 case of metachronous urothelial cancer (contralateral kidney).The total operative duration did not decrease with increasing experience (r = 0.174, p = 0.534). In contrast, there was a significant, inverse, strong correlation between the console time relative to the total operative duration and the number of conducted procedures after adjusting for the degree of adhesions and the type of urinary diversion(r = -0.593, p = 0.02). Conclusions These data suggest that en bloc simultaneous robot-assisted radical cystectomy and nephro-ureterectomy can be safely conducted with satisfactory mid-term oncological outcomes. With increasing experience, improved performance was detectable for the console surgeon but not in terms of the total operative duration. Simulation training of all team members for highly complex procedures might be a suitable approach for improving team performance. Trial registration: Not applicable.

Background Upper tract urothelial carcinoma (UTUC) is clinically understudied, and there are no definitive recommendations regarding timing of perioperative chemotherapy. The objective of this study was to compare 3 treatment pathways in UTUC: nephroureterectomy (NU) alone, neoadjuvant chemotherapy (NAC), and adjuvant chemotherapy (AC) using a microsimulation model. Patients and Methods An individual-level state transition model was constructed using TreeAgePro software to compare treatment strategies for patients with newly diagnosed UTUC. The base case was that of a 70-year-old patient with a radiographically localized upper tract tumor. Primary outcome was quality-adjusted life expectancy. Secondary outcomes included crude overall survival, rates of adverse events, and bladder cancer diagnoses. Results A total of 100,000 patients were simulated. NAC was preferred, with an estimated quality-adjusted life expectancy of 7.50 years versus 6.79 years with NU alone and 7.23 years with AC. Median crude overall survival was 123 months with NAC, 96 months with NU only, and 111 months with AC. Overall, 40.0% of patients in the AC group with invasive pathology completed chemotherapy. In the NAC group, 83.3% of patients completed chemotherapy. In the NAC group, 37.5% of patients experienced an adverse chemotherapy event compared to 15.1% of patients in the AC group. Bladder cancer recurrence rates were 64.9%, 65.9%, and 67.4% over the patient’s lifetime for the NU, NAC, and AC strategies, respectively. Conclusion This study supports the increased use of NAC in UTUC until robust randomized trials are completed. The ultimate choice should be based on patient and tumor factors.

Introduction: According to the Urology guidelines, in selected cases of distal upper tract urothelial carcinoma (UTUC) segmental ureterectomy (SU) can be offered. There is no consensus in the surgical technique of preference. Robot-assisted SU could be an option to overcome all the limitations of open and laparoscopic techniques. We describe our first experience of robot assisted SU with psoas hitch ureteral reimplantation (RAPHUR). Materials and methods: 11 patients underwent RAPHUR for distal UTUC between 2013 and 2017 in a single centre. Pre-, intra-, and postoperative outcomes were assessed. Conventional imaging was performed after 1, 3, 6 months and 1 year from surgery as follow up protocol. We retrospectively evaluated the technical feasibility, oncological and functional outcomes. Results: Median age was 71 years (57-91). The median length of the ureteral defect was 23 mm (10-40). Median preoperative creatinine level was 1.22 mg/dl (0.7-1.85) and median eGFR was 57.5 ml/min/1.73m2 (31-80). Five (45.5%) patients were symptomatic and 7 (63.6%) had hydronephrosis. Median operative time was 185 min (120-240), with a median blood loss of 100 ml (50-300). No case required conversion to open surgery. Overall, only 1 (9%) patient developed Clavien Dindo ≥ 3 postoperative complications. Average hospital stay was 7 (2-9) days. Mean postoperative creatinine was 1.05 mg/dl (0.8-1.85) and mean postoperative eGFR was 72 (36-83). During a median follow up time of 25.5 months (12-53), 4 (36.4%) patients experienced recurrence of urothelial cancer at conventional imaging follow up and 2 (18.2%) died due to its progression. Conclusions: In our initial experience RAPHUR can be proposed to selected cases of distal ureteral carcinoma with optimal perioperative and functional outcomes. However, cancer control may be undermined compared to nephroureterectomy. Thus, further prospective studies are needed to confirm our findings.

BackgroundThe advantages of photodynamic diagnostic technology using 5-aminolevulinic acid (ALA-PDD) have been established. The aim of this prospective cohort study was to evaluate the usefulness of ALA-PDD to diagnose upper tract urothelial carcinoma (UT-UC) using the Olympus VISERA ELITE video system.MethodsWe carried out a prospective, interventional, non-randomized, non-contrast and open label cohort pilot study that involved patients who underwent ureterorenoscopy (URS) to detect UT-UC. 5-aminolevulinic acid hydrochloride was orally administered before URS. The observational results and pathological diagnosis with ALA-PDD and traditional white light methods were compared, and the proportion of positive subjects and specimens were calculated.ResultsA total of 20 patients were enrolled and one patient who had multiple bladder tumors did not undergo URS. Fifteen of 19 patients were pathologically diagnosed with UT-UC and of these 11 (73.3%) were ALA-PDD positive. Fourteen of 19 patients were ALA-PDD positive and of these 11 were pathologically diagnosed with UC. For the 92 biopsy specimens that were malignant or benign, the sensitivity for both traditional white light observation and ALA-PDD was the same at 62.5%, whereas the specificities were 73.1% and 67.3%, respectively. Of the 38 specimens that were randomly biopsied without any abnormality under examination by both white light and ALA-PDD, 11 specimens (28.9%) from 5 patients were diagnosed with high grade UC. In contrast, four specimens from 4 patients, which were negative in traditional white light observation but positive in ALA-PDD, were diagnosed with carcinoma in situ (CIS).ConclusionsOur results suggest that ALA-PDD using VISERA ELITE is not sufficiently applicable for UT-UC. Nevertheless, it might be better particularly for CIS than white light and superior results would be obtained using VISERA ELITE II video system.Trial registration: The present clinical study was approved by the Okayama University Institutional Review Board prior to study initiation (Application no.: RIN 1803–002) and was registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (Accession no.: UMIN000031205).

The risk of developing urothelial carcinoma of the bladder (UCB) in patients treated by radical nephroureterectomy (RNU) for an upper urinary tract urothelial carcinoma (UTUC) is 22% to 47% in the 2 years after surgery. Subject of debate remains whether UTUC and the subsequent UCB are clonally related or represent separate origins. To investigate the clonal relationship between both entities, we performed targeted DNA sequencing of a panel of 41 genes on matched normal and tumor tissue of 15 primary UTUC patients treated by RNU who later developed 19 UCBs. Based on the detected tumor‐specific DNA aberrations, the paired UTUC and UCB(s) of 11 patients (73.3%) showed a clonal relation, whereas in four patients the molecular results did not indicate a clear clonal relationship. Our results support the hypothesis that UCBs following a primary surgically resected UTUC are predominantly clonally derived recurrences and not separate entities., What's new? Patients treated by radical nephroureterectomy for upper urinary tract cancer have an increased risk of developing bladder carcinoma following surgery. It remains unclear, however, whether the upper urinary tract cancer and subsequent bladder carcinoma are clonally related or have separate origins. This targeted DNA sequencing study shows that almost 75% of patients have tumors that are clonally related, suggesting that seeding of tumor cells is the main mechanism of bladder carcinoma development following radical nephroureterectomy. This result underscores the need to minimalize the risk of seeding during surgery and/or diagnostic ureterorenoscopy plus biopsy, and to apply peri‐operative intravesical instillations with chemotherapy.

Objective To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). Patients and methods We included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin- or carboplatin-based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence-free, cancer-specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. Results Of 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006-2010), 58% (2011-2015), to 79% (2016-2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW-adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin-based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin- and carboplatin-based regimens. Conclusions The use of NAC for high-risk UTUC increased significantly after 2010. Platinum-based short-term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.

Purpose: Intensified treatment such as extended lymph node dissection (LND) and/or perioperative chemotherapy in addition to radical nephroureterectomy (RNU) has been suggested for high-risk cases of upper tract urothelial carcinoma (UTUC). We aimed to identify preoperative predictors of tumour stage and prognosis in the diagnostic work-up before RNU. Further to evaluate if our findings could be used in selecting patients for intensified treatment. Patients and methods: A total of 179 patients treated with RNU for UTUC at Haukeland University Hospital (HUS) and Vestfold Hospital Trust (VHT) during 2005–2017 were included in this retrospective study. All relevant preoperative variables regarding the patient, the CT and the ureteroscopy (URS) were registered and analysed regarding their ability to predict non-organ confined disease (NOCD, pT3þ and/or Nþ) at final pathology after RNU. The prognosis was assessed calculating survival for the cohort and stratified by preoperative variables. Results: Local invasion and pathological lymph nodes at CT predicted NOCD in uni and multivariate regression analyses (OR 3.36, p¼.004 and OR 6.21, p¼.03, respectively). Reactive oedema surrounding the tumour (OR 2.55, p¼.02), tumour size (4.8 vs. 3.9 cm, p¼.006) and high-grade tumour at URS biopsy (OR 3.59, p¼.04) predicted NOCD at univariate regression analyses. The 5-year CSS and OS for the entire cohort was 79% and 60%. ECOG, local invasion, pathological lymph nodes and reactive oedema surrounding the tumour at CT predicted CSS. Conclusions: Several variables at the CT predicted both stage and survival. Local invasion at CT seems the most promising feature for selecting patients for intensified treatment. publishedVersion

We report the reliability of computerized tomography urography and ureteroscopy in the diagnosis and management of upper tract urothelial carcinoma.From 2015 to November 2018 we prospectively collected and retrospectively analyzed 244 cases of ureteroscopy with available preoperative computerized tomography urography. Computerized tomography urography was categorized as positive, suspicious, unlikely and negative. Correspondence between imaging, ureteroscopy and histology was analyzed. The therapeutic indication, based on 2020 EAU Guidelines and patient clinical data, was recorded before and after ureteroscopy. Cohen's Kappa was used for agreement analysis. Logistic regression was used for prediction of positive ureteroscopy.Ureteroscopy was positive for upper tract urothelial carcinoma in 107/115 (93%), 48/77 (62.3%), 15/27 (55.6%) and 12/25 (48%) cases with positive, suspicious, unlikely and negative computerized tomography urography, respectively. On cytohistology the result was confirmed in 164/182 (90.1%) cases. The positive predictive value of a filling defect, stenosis, thickening and hydronephrosis on computerized tomography urography was 87.7% (121/138 cases), 65.6% (21/32), 69.6% (64/92) and 79.7% (59/74), respectively. On multivariate analysis a filling defect (95% CI 2.76-11.5, OR 5.63, p0.0001) or hydronephrosis (1.04-6.18, OR 2.52, p=0.04) was associated with ureteroscopy outcome. Among cases with positive computerized tomography urography and ureteroscopy, the lesions differed in dimensions (20/107), number (14/107) and site (11/107), for a total of 45/107 (42.1%) cases. The indication of elective treatment changed after ureteroscopy in 37/76 (48.1%) cases (Kappa=0.31), as 17/28 (60.7%), 11/20 (55%) and 11/28 (39.2%) indications were confirmed for endoscopic management, ureterectomy and nephroureterectomy, respectively.The complementary use of computerized tomography urography and ureteroscopy in the diagnostic workup of upper tract urothelial carcinoma should be evaluated.

Upper tract urothelial carcinoma is a rare malignancy for which surgery provides definitive management. Open radical nephroureterectomy was the gold standard treatment, but laparoscopic and robot-assisted approaches are alternative options. Kidney-sparing approaches are feasible for carefully selected patients with ureteral cancer. This article discusses the evaluation of patients with upper tract urothelial carcinoma and definitive management using robot-assisted surgical approaches. Patients with urothelial carcinoma of the upper tract can be treated with robot-assisted nephroureterectomy, distal ureterectomy, and segmental ureterectomy.

Discriminating between urothelial carcinoma (UC), including bladder cancer (BCa) and upper urinary tract UC (UTUC), is often challenging. Thus, the current study evaluated the diagnostic performance of N‐glycosylation signatures of immunoglobulins (Igs) for detecting UC, including BCa and UTUC. N‐glycosylation signatures of Igs from serum samples of the training cohort, including 104 BCa, 68 UTUC, 10 urinary tract infection, and 5 cystitis cases, as well as 62 healthy volunteers, were measured retrospectively using automated capillary‐electrophoresis‐based N‐glycomics. UTUC or BCa scores were then established through discriminant analysis using N‐glycan signatures of Igs. Diagnostic performance was evaluated using the area under receiver operating characteristics curve (AUC) and decision curve analyses (DCA). Our result showed that BCa and UTUC scores for discriminating BCa (AUC: 0.977) and UTUC (AUC: 0.867), respectively, provided significantly better clinical performance compared to urine cytology, gross hematuria, or clinical T1 cases. DCA revealed that adding BCa and UTUC scores to gross hematuria status was the best combination for detecting UC and avoiding the need for more intervention without overlooking UC (risk threshold: 13%–93%). The UC nomogram based on the combination of gross hematuria, UTUC score, and BCa score could detect UC with an AUC of 0.891, indicating significantly better performance compared to gross hematuria status in the validation cohort (251 patients). The limitations of this study include its small sample size and retrospective nature. The UC nomogram based on gross hematuria and N‐glycosylation signatures of Igs can be a promising approach for the diagnosis of UC., We evaluated the diagnostic performance of Bladder cancer (BCa) and upper urinary tract urothelial carcinoma (UTUC) discrimination scores that we developed based on N‐glycosylation signatures of immunoglobulins. The BCa score and UTUC score provided significantly better clinical performance than urine cytology negative or gross hematuria negative or clinical T1 cases.

Purpose To register all cases of urothelial cancer and renal cell carcinoma (RCC) in Norway during 1999–2018 to obtain the contemporary incidence of UTUC and UTUC incidence relative to other urothelial cancers and RCC. Further to analyse possible changes over time regarding UTUC incidence, UTUC patient characteristics, tumour characteristics and survival. Methods 3502 cases registered with ICD code C65 and C66 during 1999–2018 at the Norwegian cancer registry were entered into a database. After a selection process 3096 cases were included in the study. The crude incidences of UTUC were calculated for each year adjusting for the corresponding population data. Age-standardized rates adjusting to the European standard population (2013) were calculated. Comparisons were made with other cases of urothelial cancer and RCC. For changes over time, the material was split into 5-year periods. Regression analysis was used to calculate yearly changes and for assessing statistical significance. Survival outcomes were calculated using the Kaplan–Meier method. Results The overall age-standardized incidence rate was 3.88, increasing from 3.21 to 4.70 from first to last 5-year periods. The increase affected all ages except those Conclusion The incidence of UTUC was higher than expected and increasing. Patient age at diagnosis was increasing.

Purpose: To evaluate the efficacy and safety of RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E, in patients with HER2+ locally advanced or metastatic urothelial carcinoma (mUC) refractory to standard therapies. Patients and Methods: This was a phase II, open-label, multicenter, single-arm study of patients with HER2+ (IHC status 3+ or 2+) locally advanced or mUC who previously failed at least one line of systemic chemotherapy. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent review committee (BIRC). The secondary endpoint included progression-free survival (PFS), disease control rate, duration of response, overall survival (OS), and safety. Results: Forty-three patients were enrolled. The median follow-up was 20.3 months. The overall confirmed ORR as assessed by the BIRC was 51.2% [95% confidence interval (CI), 35.5%–66.7%]. Similar responses were observed in prespecified subgroups, such as those with liver metastasis and those previously treated with anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapies. The median PFS and OS were 6.9 months (95% CI, 5.6–8.9) and 13.9 months (95% CI, 9.1–NE), respectively. The most common treatment-related adverse events (TRAE) were hypoesthesia (60.5%), alopecia (55.8%), and leukopenia (55.8%). Twenty-five (58%) patients experienced grade 3 TRAEs, including hypoesthesia (23.3%) and neutropenia (14.0%). No grade 4 or grade 5 TRAEs occurred. Conclusions: RC48-ADC demonstrated a promising efficacy with a manageable safety profile in patients with HER2+ locally advanced or mUC who had failed at least one line of systemic chemotherapy.

Introduction: The diffusion-weighted imaging (DWI) technique with intravoxel incoherent motion model enables the estimation of capillary blood volume as a perfusion-related parameter- (PP-) value. Therefore, the PP-value of the kidney theoretically reflects renal capillary blood volume. We analyzed the usefulness of the PP-value in estimating postoperative renal function in upper-tract urothelial carcinoma (UTUC) patients. Methods: Forty-eight consecutive patients who underwent magnetic resonance imaging before radical nephroureterectomy from 2011 to 2018 were analyzed. A PP-map displaying PP-values on a pixel-by-pixel basis was created from DWI signals (b-values of 0, 500, and 1,000 s/mm2). Two readers independently analyzed the renal PP-value. DWI-based split renal function (SRF) of the intact kidney was calculated by splitting serum Cr-based preoperative estimated glomerular filtration rates (eGFRs). The predictive accuracy of the method was evaluated using renography as the reference standard. Results: Interobserver analysis revealed an excellent correlation value of 0.97. The SRF value showed a good linear correlation with the observed postoperative eGFR (r = 0.76, p < 0.001). The predictive accuracy of the DWI-based method was similar to that of the nuclear-based method. Conclusion: This DWI-based evaluation of capillary blood volume provides a noninvasive tool for predicting the postoperative renal function, thereby facilitating the management of UTUC patients.

Objectives: The aim of the study was to evaluate the impact of fluorescence in situ hybridization (FISH) diagnostics on the T stage in final histology specimen of patients undergoing radical nephroureterectomy (RNU) due to upper tract urothelial carcinoma (UTUC) at a large tertiary care center. Methods: We retrospectively analyzed patients who underwent RNU at our center between 2008 and 2020. Inclusion criteria were RNU due to UTUC. Urine cytologies were used for FISH analysis to detect chromosomal abnormalities. Pre-FISH group was defined as patients without access to routine preoperative urinary FISH testing (2008–2014), and FISH group was defined as patients with access to routine FISH testing. Primary outcome was T stage in final histology. Statistical analysis was performed by χ2 test and Mann-Whitney U test. Results: Out of 212 patients who underwent RNU at our center between 2008 and 2020, 155 patients were included into the final analysis. The median age was 71 (range 33–90) years, and 108 (69.7%) patients were male and 47 (30.3%) female. Age and gender were not differently distributed in both groups (age: p = 0.925; gender: p = 0.682). Organ-confined disease was found in 37/72 patients in the pre-FISH cohort and in 48/83 patients in the FISH cohort (p = 0.422). Within organ-confined disease, 18/37 patients revealed a T stage smaller than T1 in the pre-FISH cohort and 35/48 patients in the FISH cohort (p = 0.022). Conclusions: Preoperative FISH diagnostics add important information to preoperative diagnostic workup of patients with UTUC. Within organ-confined disease, a significant shift toward T stages lower than T1 is observed. Further research is required to determine the impact of this shift on survival in UTUC.

Background IgG4-related kidney disease causes renal impairment of unknown pathogenesis that may progress to kidney failure. Although ectopic germinal centers contribute to the pathogenesis of the head and neck lesions of IgG4-related disease, the presence of tertiary lymphoid tissue (TLT) containing germinal centers in IgG4-RKD has rarely been reported. Case presentation We report a 72-year-old Japanese man who had IgG4-related tubulointerstitial nephritis (TIN) with TLT formation incidentally detected in a resected kidney with mass lesion of IgG4-related ureteritis in the ureteropelvic junction. During follow-up for past surgical resection of a bladder tumor, renal dysfunction developed and a ureter mass was found in the right ureteropelvic junction, which was treated by nephroureterectomy after chemotherapy. Pathology revealed no malignancy but abundant IgG4-positive cell infiltration, obliterative phlebitis and storiform fibrosis, confirming the diagnosis of IgG4-related ureteritis. In the resected right kidney, lymphoplasmacytes infiltrated the interstitium with focal distribution in the renal subcapsule and around medium vessels without storiform fibrosis, suggesting the very early stage of IgG4-TIN. Lymphocyte aggregates were also detected at these sites and consisted of B, T, and follicular dendritic cells, indicating TLT formation. IgG4-positive cells infiltrated around TLTs. Conclusions Our case suggests that TLT formation is related with the development of IgG4-TIN and our analysis of distribution of TLT have possibility to elucidate IgG4-TIN pathophysiology.

Objective: The objective of this study is to evaluate the effect of diagnostic ureterorenoscopy (URS) prior to radical nephroureterectomy (RNU) on intravesical recurrence (IVR), in patients with primary upper urinary tract urothelial carcinoma (UTUC). Materials and Methods: Retrospective analysis of 354 patients, who underwent RNU for UTUC from 10 urology centers between 2005 and 2019, was performed. The primary endpoint was the occurrence of IVR after RNU. Patients were divided into URS prior to RNU (Group 1) and no URS prior to RNU (Group 2). Rates of IVR after RNU were compared, and a Cox proportional hazards model was used to evaluate potential predictors of IVR. Results: After exclusion, a total of 194 patients were analyzed: Group 1 n = 95 (49.0%) and Group 2 n = 99 (51.0%). In Group 1, a tumor biopsy and histopathological confirmation during URS were performed in 58 (61.1%). The mean follow-up was 39.17 ± 39.3 (range 12–250) months. In 54 (27.8%) patients, IVR was recorded after RNU, and the median recurrence time within the bladder was 10.0 (3–144) months. IVR rate was 38.9% in Group 1 versus 17.2% in Group 2 (p = 0.001). In Group 1, IVR rate was 43.1% in those undergoing intraoperative biopsy versus 32.4% of patients without biopsy during diagnostic URS (p =0.29). Intravesical recurrence-free survival (IRFS) was longer in Group 2 compared to Group 1 (median IRFS was 111 vs. 60 months in Groups 2 and 1, respectively (p< 0.001)). Univariate analysis revealed that IRFS was significantly associated with URS prior to RNU (HR: 2.9, 95% CI 1.65–5.41; p < 0.001). In multivariate analysis, URS prior to RNU (HR: 3.5, 95% CI 1.74–7.16; p < 0.001) was found to be an independent prognostic factor for IRFS. Conclusion: Diagnostic URS was associated with the poor IRFS following RNU for primary UTUC. The decision for a diagnostic URS with or without tumor biopsy should be reserved for cases where this information might influence further treatment decisions.

Objective To assess the impact of neoadjuvant chemotherapy (NAC) on survival outcomes in a contemporary cohort of patients with in upper tract urothelial carcinoma (UTUC). Methods The National Cancer Database was queried from 2004 to 2015 to identify subjects who underwent nephroureterectomy for UTUC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between patients who received preoperative chemotherapy to those who did not at each pathologic (p) TNM stage group: T1-4N0, N+, and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis. Results A total of 10,315 chemoeligible subjects were included in the analysis. A total of 296 (2.9%) of patients received NAC prior to NU. Kaplan-Meier survival curves of the entire cohort demonstrated an overall survival advantage associated with administration of NAC (P = .017). Stratified by clinical staging, subjects with nonorgan-confined tumors had improved overall survival outcomes with NAC administration (P = .012). On multivariate analysis there was a statistically significant improvement in overall survival between in patients who received NAC. Of patients in the preoperative chemotherapy group who had clinically nonorgan-confined disease, 27.1% had organ-confined disease at time of surgery compared to 1.4% of those who underwent surgery as initial therapy. Conclusion In a contemporary cohort of subjects who underwent nephroureterectomy for UTUC, administration of NAC in patients with high-grade nonorgan-confined disease led to higher rates of pathologic downstaging and was associated with improved overall survival.

OBJECTIVES To identify the prognosis of patients with non-urothelial carcinoma of the upper urinary tract and compare it with that of patients with urothelial carcinoma. METHODS We used hospital-based cancer registry data in Japan to extract histologically confirmed non-urothelial carcinoma and urothelial carcinoma cases of the upper urinary tract diagnosed in 2008-2009. We estimated the 5-year overall survival by a Kaplan-Meier analysis. The Cox proportional hazards regression analysis was used to evaluate prognostic factors. RESULTS A total of 2567 upper urinary tract cancer patients with confirmed histological subtypes were identified. The most common histology of non-urothelial carcinoma was squamous cell carcinoma (n = 88, 3.4%) followed by adenocarcinoma (n = 33, 1.3%) and small cell carcinoma (n = 10, 0.4%). The proportion of advanced stage in the squamous cell carcinoma patients was significantly higher than that in the urothelial carcinoma patients (P = 0.003). In stage IV, the proportion of patients who received a combination of surgery + chemotherapy in the urothelial carcinoma group was higher than that in the non-urothelial carcinoma group (34% vs 16%, respectively). The 5-year overall survival rates of the non-urothelial carcinoma patients at stages I-III and stage IV were significantly worse than those of the urothelial carcinoma patients (P = 0.003, P

Objectives To investigate the impact of the remnant ureteral orifice (RUO) on the prognosis of upper tract urothelial carcinoma (UTUC), because the presence of an ipsilateral intact ureteral orifice is not an uncommon finding during follow-up cystoscopy despite the clinical relevance of bladder cuffing during radical nephroureterectomy (RNU) for the management of UTUC. Methods The records of patients who underwent RNU in all tertiary hospitals in Daegu province (2011-2018) were retrospectively reviewed. Subjects were allocated to RUO or non-RUO groups. Cox proportional hazard models were used to identify variables. The primary endpoint was a 5-year intravesical recurrence-free survival (RFS). Results Of the 164 patients enrolled, 45 (27.4%) had an RUO by postoperative cystoscopy. The characteristics of the RUO and non-RUO groups were similar. During mean follow-up of 76.4 months (range: 69.5-83.4), 21 (46.7%) subjects in the RUO group and 25 (21.0%) in the non-RUO group experienced intravesical recurrence (P = .001). Among them, 3 (6.7%) and 14 (8.5%) developed distant metastasis (P = .339), and 3 (6.7%) and 9 (7.6%) succumbed to UTUC (P = .844), respectively. The 5-year RFS was lower in the RUO group than in the non-RUO counterpart (45.6% vs 77.8%, P = .003). Multivariate analysis showed lymphovascular invasion (hazard ratio [HR] = 3.593, P = .002), lymph nodal involvement (HR = 2.336, P = .038), and the presence of RUO (HR = 2.058, P = .026) predicted 5-year RFS. Conclusion The presence of RUO after RNU was found to be significantly associated with intravesical tumor recurrence, and this finding emphasizes the quality of bladder cuffing during RNU, which could be assessed by complete removal of the natural orifice.

Purpose The accurate selection of patients who are most likely to benefit from neoadjuvant chemotherapy is an important challenge in oncology. Serum AGR has been found to be associated with oncological outcomes in various malignancies. We assessed the association of pre-therapy serum albumin-to-globulin ratio (AGR) with pathologic response and oncological outcomes in patients treated with neoadjuvant platin-based chemotherapy followed by radical nephroureterectomy (RNU) for clinically non-metastatic UTUC. Methods We retrospectively included all clinically non-metastatic patients from a multicentric database who had neoadjuvant platin-based chemotherapy and RNU for UTUC. After assessing the pretreatment AGR cut‐off value, we found 1.42 to have the maximum Youden index value. The overall population was therefore divided into two AGR groups using this cut‐off (low, . A logistic regression was performed to measure the association with pathologic response after NAC. Univariable and multivariable Cox regression analyses tested the association of AGR with OS and RFS. Results Of 172 patients, 58 (34%) patients had an AGR p = 0.47) nor RFS HR 1.48 (95% CI 0.98–1.22; p = 0.06). These results remained true regardless of the response to NAC. Conclusion Pre-therapy low serum AGR before NAC followed by RNU for clinically high-risk UTUC was not associated with pathological response or long-term oncological outcomes. Biomarkers that can complement clinical factors in UTUC are needed as clinical staging and risk stratification are still suboptimal leading to both over and under treatment despite the availability of effective therapies.

Background Endoscopic management of low risk upper tract urothelial carcinoma (UTUC) may be considered in select clinical scenarios, which allows sparing the morbidity of radical nephroureterectomy while achieving acceptable oncological outcomes and preservation of kidney function. Herein, we present a case with UTUC in a solitary kidney managed with 532 nm laser vaporization through a percutaneous approach. Case presentation The patient in this video (Additional file 1) is an 85-year-old woman who presented with a bulky tumor in the collecting system of a congenital solitary left kidney, which was a biopsy proven low grade urothelial carcinoma. Prior to the procedure, a lower pole percutaneous nephrostomy tube was successfully placed under sedation by Interventional Radiology. The procedure was done in a prone split leg position. The mass, which was predominantly localized to the renal pelvis was efficiently vaporized with the 532 nm laser in a systematic manner with continuous irrigation of normal saline through the cystoscope. The patient was discharged home on postoperative day 2 with the nephroureterostomy catheter open to drainage. This catheter was subsequently clamped and removed two weeks later without complications. Follow up uretroscopy showed excellent treatment response and the patient remains well without complications. Conclusion This case report details the potential utility of 532 nm laser vaporization of UTUC, however, ongoing studies are required to demonstrate peri-operative safety and durable oncologic efficacy.

This prospective randomized comparative trial study aimed to evaluate the therapeutic outcomes of radical nephroureterectomy and adjuvant chemotherapy (ACT) used in combination in high risk upper tract urothelial carcinoma (UTUC) patients with cardiovascular comorbidity. Based on the inclusion criteria of high-risk UTUC in EAU guidelines (updated in 2014), all eligible patients treated in our hospital from January 2014 to March 2018 were included, and cases with late disease, renal dysfunction, severe cardiopulmonary disease or other malignant tumors were excluded. The cases were randomized into two groups based on treatment regimen. Multivariate analyses were performed to analyze the influencing factors of survival outcome in the enrolled patients. The Cox proportional-hazards model and the Kaplan–Meier method were employed to assess progression free survival (PFS), overall survival (OS) and cancer specific survival (CSS). In addition, the potential adverse effects of chemotherapy were actively monitored. A total of 176 high-risk UTUC individuals with cardiovascular comorbidity were enrolled and evaluated in this study. Median follow-up durations were 30 months (range 6–54) in the RNU (n = 82) group and 36 months (range 6–54) in the RNU + ACT (n = 94) group. Multivariable analysis indicated that peri-operative cardiovascular events risk grade was independent prognostic factor for OS. Tumor size was independent prognostic factor for PFS and CSS. BMI and lymphovacular invasion were significant predictors of PFS. Clinical stage, lymph node involvement, and tumor grade were significant predictors of PFS, OS and CSS in these patients. Especially, chemotherapy was helpful in improving PFS [P P = 0.013, HR = 2.336 (1.956–2.883)] and CSS [P = 0.008, HR = 3.073 (2.533–3.738)]. Kaplan–Meier analysis demonstrated that the oncologic outcomes of RNU treated high-risk UTUC patients were improved much significantly by ACT, including PFS [P = 0.0033, HR = 3.78 (3.13–4.55)], OS [P = 0.0397, HR = 1.39 (1.01–1.75)] and CSS [P = 0.0255, HR = 1.26 (1.07–1.45)]. Further analysis of the lymph node positive subgroup showed that the median time of oncologic events was enhanced in RNU + ACT treated individuals in comparison with the RNU group, including PFS (11.4 months vs. 31.9 months, P = 0.0018), OS (26.8 months vs. 36.3 months, P = 0.0255) and CSS (28.2 months vs. 39.3 months, P = 0.0197). In the T3/4 cohort, significantly increased median PFS (13.9 months vs. 36.3 months, P = 0.0217), OS (20.6 months vs. 32.2 months, P = 0.0183) and CSS (21.9 months vs. 38.4 months, P = 0.0226) were obtained in the combination group. Additionally, no severe adverse events (over grade 4) associated with chemotherapy were detected in the RNU + ACT group. In conclusion, ACT after radical surgery has statistically significant therapeutic effects on PFS, OS and CSS in high-risk UTUC patients with cardiovascular comorbidity.

Objectives To assess the impact of two cycles of neoadjuvant chemotherapy (NAC) in patients who underwent nephroureterectomy for high-risk cN0M0 upper tract urothelial carcinoma (UTUC), and to evaluate the efficacy of NAC in patients with localised disease (≤cT2). Patients and methods We retrospectively analysed patients with high-risk cN0M0 UTUC who received NAC followed by surgery, compared with a matched cohort who underwent initial surgery at Fujita Health University during 2005-2019. Baseline and tumour characteristics, overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were compared between the cohorts. Cox proportional hazards models were used to identify predictors of survival. Results There were 117 and 67 patients in the study group and the control group, respectively. Significantly higher pathological downstaging (pDS) and lower lymphovascular invasion (LVI) were observed in the study group than in the control group (48% vs 22%, P = 0.008 and 29% vs 46%, P = 0.045, respectively). The NAC group had significantly better 5-year OS (79% vs 53%, P = 0.003), 5-year CSS (84% vs 66%, P = 0.008), and 5-year RFS (80% vs 61%, P = 0.001) than the control group. The OS benefit of NAC was observed even in patients with localised (≤cT2) disease (P = 0.019). Patients with LVI showed significantly worse CSS both in pathologically locally advanced (≥pT3) and in localised (≤pT2) tumours (P = 0.048 and P = 0.018, respectively). Multivariate analysis identified LVI, NAC, and pDS as independent predictors of OS. Male sex and post-NAC LVI were identified as predictors of worse survival in patients who underwent NAC. Conclusions Two cycles of NAC improved the survival of patients with high-risk UTUC, even in patients with localised disease. Although two cycles of NAC appear to be effective in cN0M0 high-risk UTUC including localised disease, additional larger sample size multicentre prospective studies comparing short-course NAC regimens followed by surgery and surgery alone are required.