Search

Objective: To analyse surgical, functional, and mid‐term oncological outcomes of robot‐assisted nephroureterectomy (RANU) in a contemporary large multi‐institutional setting. Patients and Methods: Data were retrieved from the ROBotic surgery for Upper tract Urothelial cancer STtudy (ROBUUST) 2.0 database, an international, multicentre registry encompassing data of patients with upper urinary tract urothelial carcinoma undergoing curative surgery between 2015 and 2022. The analysis included all consecutive patients undergoing RANU except those with missing data in predictors. Detailed surgical, pathological, and postoperative functional data were recorded and analysed. Oncological time‐to‐event outcomes were: recurrence‐free survival (RFS), metastasis‐free survival (MFS), cancer‐specific survival (CSS), and overall survival (OS). Survival analysis was performed using the Kaplan–Meier method, with a 3‐year cut‐off. A multivariable Cox proportional hazard model was built to evaluate predictors of each oncological outcome. Results: A total of 1118 patients underwent RANU during the study period. The postoperative complications rate was 14.1%; the positive surgical margin rate was 4.7%. A postoperative median (interquartile range) estimated glomerular filtration rate decrease of −13.1 (−27.5 to 0) mL/min/1.73 m2 from baseline was observed. The 3‐year RFS was 59% and the 3‐year MFS was 76%, with a 3‐year OS and CSS of 76% and 88%, respectively. Significant predictors of worse oncological outcomes were bladder‐cuff excision, high‐grade tumour, pathological T stage ≥3, and nodal involvement. Conclusions: The present study contributes to the growing body of evidence supporting the increasing adoption of RANU. The procedure consistently offers low surgical morbidity and can provide favourable mid‐term oncological outcomes, mirroring those of open NU, even in non‐organ‐confined disease. [ABSTRACT FROM AUTHOR]

Background: Systemic and local recurrences of urothelial bladder cancer (UBC) significantly impair survival after radical cystectomy (RC), but little is known about the impact of the recurrence of urothelial cancer in the upper urinary tract (UTUC). This report describes survival outcomes and their predictors for patients who underwent RC followed by radical nephroureterectomy (RNU) for UTUC. Methods: The Surveillance, Epidemiology, and End Results database was queried to identify patients who underwent RC for UBC and subsequent RNU for UTUC. The Kaplan–Meier method and competing-risk Cox regression (CRR) were used for the survival analysis. Results: Overall, 102 patients have undergone RNU within a median of 49 months (interquartile range [IQR], 27–76 months) since RC. Muscle-invasive UTUCs were predominant at RNU (n = 58; 56.7%), but organ-confined bladder tumors were most frequent at RC (n = 42, 41.5%). After RNU, the estimated 5-year overall survival (OS) was 25.9%, the cancer-specific survival (CSS) was 35.6%, the median OS was 23 months (IQR, 11–63 months), and the CSS was 34 months (IQR, 13–132 months). In the multivariable CRR, the factors predictive for CSS after RNU included male gender (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.03–5.42; p < 0.05), muscle-invasive UTUC (HR, 2.20; 95% CI, 1.13–4.28; p < 0.05), and the presence of distant metastasis (HR,11.59; 95% CI, 5.33–25.2; p < 0.001). Conclusions: In conclusion, the patients who underwent RNU for UTUC after RC for UBC experienced poor OS and CSS. The majority of RNUs were performed for locally advanced tumors. The independent risk factors for worse OS and CSS after RNU were UTUC T stage, presence of metastasis, and male gender. [ABSTRACT FROM AUTHOR]

Introduction: Upper urinary tract urothelial cancer is a rare, aggressive variant of urinary tract cancer. There is often delay to diagnosis and management for this entity in view of diagnostic and staging challenges needing additional investigations and risk stratifications for improved outcomes. In this article, we share our experience in developing a dedicated diagnostic and treatment pathway for UTUC and assess its impact on time lines to radical nephroureterectomy (RNU). We also evaluate the impact of diagnostic ureteroscopy (DUR) on UTUC care pathways timelines. Materials and methods: A prospective database was maintained for all patients who underwent a RNU from January 2015 to August 2022 in a high-volume single tertiary care centre in the UK. In 2019, a Focused UTUC pathway (FUP) was implemented at the centre to streamline diagnostic and RNU pathways. A retrospective analysis of the database was conducted to compare time lines and diagnostic trends between the pre-FUP and FUP cohorts. Primary outcome measures were time to RNU from MDT. Secondary outcome measures were: impact of DUR on time to RNU from MDT and negative UTUC rates between DUR and non-DUR cohorts. Differences in continuous variables across categories were assessed using the independent sample t test. Categorical variables between cohorts were analysed using the chi-square (χ2). Statistical significance in this study was set as p < 0.05. Results: A total of 500 patients with complete data were included in the analysis. The pre-FUP and FUP cohorts consisted of 313 patients and 187 patients, respectively. The overall cohort had a mean age (SD) of 70 years (9.3). 66% of the overall cohort were males. The median time to RNU from MDT in the FUP was significantly lower compared to the pre-FUP cohort; 62 days (IQR 59) vs. 48 days (IQR 41.5), p < 0.0001. The median time to RNU from MDT in patients who underwent a diagnostic URS in the FUP cohort was significantly lower compared to the pre-FUP cohort; 78.5 days (IQR 54.8) vs. 68 days (IQR 48), p-NS. The non-UTUC rates in the DUR and non-DUR cohorts were 6/248 (2.4%) and 14/251 (5.6%), respectively (NS). Conclusion: In this series, we illustrate the effectiveness of integrating a multidisciplinary approach with specialised personnel, ring-fenced clinics, efficient diagnostic assessment and optimised theatre capacity. By adopting a risk-stratified approach to diagnostic ureteroscopy, we have achieved a significant reduction in time to RNU. [ABSTRACT FROM AUTHOR]

Background: Endoscopic management of upper tract urothelial cancer (UTUC) is an important treatment option for low risk UTUC. Although Taiwan is an endemic area for UTUC, endoscopic treatment outcomes in Taiwan are frequently under- reported. Methods: This study retrospectively reviewed the treatment outcomes of endoscopic management for clinically localized UTUC. Patients with biopsy or washing cytology confirmed UTUC who underwent endoscopic or percutaneous management with a curative intent were retrospectively reviewed for eligibility of analysis. Those cases without pre-intervention confirmed UTUC, and metastatic or nodal disease at diagnosis were excluded. Results: In total, 307 patients who underwent endoscopic management were reviewed and 279 cases were eligible for final analysis. With a median follow-up of 44.3 months (inter-quartile range (IQR): 23.4–76.4 months), 117 cases (46.4%) were endoscopic cured after median one session (range:1–8; IQR:1–2) of endoscopic treatment. Those endoscopic cured UTUC was associated with more small-sized tumor, more low-grade biopsied-histology, less concomitant bladder UC and less pre-operative hydronephrosis.In addition, 201(79.7%) cases among 252 cases with confirmed oncological outcome were free of UTUC at the end of follow-up and only 43 (17%) patients had a UTUC related mortality. Salvage RNU offered a better tumor free survival rate (92% vs. 77.5%) than those without salvage RNU in those UTUC refractory to endoscopic management. In multivariable analyses, pre-operative hydronephrosis was the independent risk factor for OS. Multiplicity and concomitant bladder UC were independent risk factors for DFS. Conclusions: We confirmed the consistent safety and efficacy of endoscopic management of clinical localized UTUC in a highly UTUC endemic area like Taiwan. Early salvage RNU is mandatory in those UTUC refractory to endoscopic management in prevention of UTUC related death.

Simple Summary: The benefit of lymph node dissection (LND) for node-negative (N0) upper urinary tract urothelial cancer (UTUC) remains uncertain. We aimed to evaluate the association between the extent of LND during radical nephroureterectomy (RNU) and survival by analyzing real-world population-based data. The removal of at least four lymph nodes was associated with improved overall and cancer-specific survival compared to no or less extensive LND. Propensity score matching was performed to adjust for confounders. Further risk-stratified subgroup analysis confirmed the survival benefit of more extensive LND, especially for muscle-invasive UTUC. Our findings underscore the significance of performing an adequate LND during RNU for N0 UTUC. Further prospective studies are crucial to confirm our results. The benefit of lymph node dissection (LND) during radical nephroureterectomy (RNU) in lymph node (LN)-negative (cN0/pN0) UTUC remains controversial. We aimed to assess the association between LND and its extent and survival in LN-negative UTUC. The Surveillance, Epidemiology, and End Results database was searched to identify patients with non-metastatic chemotherapy-naïve cN0/pNx or pN0 UTUC who underwent RNU +/− LND between 2004 and 2019. Overall, 4649 patients with cN0/pNx or pN0 UTUC were analyzed, including 909 (19.55%) individuals who had LND. Among them, only in 368 patients (7.92%) was LND extended to at least four LNs, and the remaining 541 patients (11.64%) have had < four LNs removed. In the whole cohort, LND contributed to better cancer-specific survival (CSS) and overall survival (OS). Furthermore, a propensity score-matched analysis adjusted for confounders confirmed that improved CSS and OS was achieved only when ≥ four LNs had been removed, especially in muscle-invasive UTUC. A multivariable analysis further confirmed an association between the extent of LND and CSS. To conclude, adequate LND during RNU was associated with improved OS and CSS in LN-negative UTUC, particularly in muscle-invasive stage. This underscores that a sufficient LN yield is required to reveal a therapeutic benefit in patients undergoing RNU. [ABSTRACT FROM AUTHOR]

Endoscopic management of upper tract urothelial cancer (UTUC) is an important treatment option for low risk UTUC. Although Taiwan is an endemic area for UTUC, endoscopic treatment outcomes in Taiwan are frequently under- reported. This study retrospectively reviewed the treatment outcomes of endoscopic management for clinically localized UTUC. Patients with biopsy or washing cytology confirmed UTUC who underwent endoscopic or percutaneous management with a curative intent were retrospectively reviewed for eligibility of analysis. Those cases without pre-intervention confirmed UTUC, and metastatic or nodal disease at diagnosis were excluded. In total, 307 patients who underwent endoscopic management were reviewed and 279 cases were eligible for final analysis. With a median follow-up of 44.3 months (inter-quartile range (IQR): 23.4–76.4 months), 117 cases (46.4%) were endoscopic cured after median one session (range:1–8; IQR:1–2) of endoscopic treatment. Those endoscopic cured UTUC was associated with more small-sized tumor, more low-grade biopsied-histology, less concomitant bladder UC and less pre-operative hydronephrosis. In addition, 201(79.7%) cases among 252 cases with confirmed oncological outcome were free of UTUC at the end of follow-up and only 43 (17%) patients had a UTUC related mortality. Salvage RNU offered a better tumor free survival rate (92% vs. 77.5%) than those without salvage RNU in those UTUC refractory to endoscopic management. In multivariable analyses, pre-operative hydronephrosis was the independent risk factor for OS. Multiplicity and concomitant bladder UC were independent risk factors for DFS. We confirmed the consistent safety and efficacy of endoscopic management of clinical localized UTUC in a highly UTUC endemic area like Taiwan. Early salvage RNU is mandatory in those UTUC refractory to endoscopic management in prevention of UTUC related death. [ABSTRACT FROM AUTHOR]

Simple Summary: In muscle-invasive bladder cancer, platinum-based neoadjuvant chemotherapy is a well-established concept, since it contributes to pathological downstaging and improves overall survival. Immunotherapy has become increasingly important in adjuvant and palliative treatment for metastatic urothelial carcinoma, and phase II studies have shown assuring data in neoadjuvant treatment before cystectomy. Although upper urinary tract urothelial cancer usually presents as more invasive at diagnosis than bladder cancer, there is no recommendation for neoadjuvant therapy before nephroureterectomy. This meta-analysis comprises eleven comparative trials on neoadjuvant chemotherapy in this setting and analyzes pathological downstaging as well as oncological outcomes. However, no comparative studies investigating immunotherapy in upper tract urothelial cancer were found. The pathological downstaging and complete response were significantly improved in patients who received neoadjuvant chemotherapy. The data also suggested a benefit in overall survival and progression-free survival in these patients. Prospective studies are needed to confirm these findings and assess the role of immunotherapy in this setting. Neoadjuvant chemotherapy is a well-established concept in muscle-invasive bladder cancer with known advantages in overall survival. Phase II trials show encouraging response rates for neoadjuvant immunotherapy before radical surgery in urothelial cancer. There is no recommendation for neoadjuvant therapy in upper tract urothelial carcinoma before nephroureterectomy. Our aim was to assess the available data on neoadjuvant chemotherapy and immunotherapy before nephroureterectomy in patients with high-risk upper tract urothelial carcinoma in terms of pathological downstaging and oncological outcomes. Two investigators screened PubMed/Medline for comparative trials in the English language. We identified 368 studies and included eleven investigations in a systematic review and meta-analysis for neoadjuvant chemotherapy and control groups. There were no comparative trials investigating immunotherapy in this setting. All 11 studies reported on overall pathological downstaging with a significant effect in favor of neoadjuvant chemotherapy (OR 5.17; 95%CI 3.82; 7.00). Pathological complete response and non-muscle invasive disease were significantly higher in patients receiving neoadjuvant chemotherapy (OR 12.07; 95%CI 4.16; 35.03 and OR 1.62; 95%CI 1.05; 2.49). Overall survival and progression-free survival data analysis showed a slight benefit for neoadjuvant chemotherapy. Our results show that neoadjuvant chemotherapy is effective in downstaging in upper urinary tract urothelial carcinoma. The selection of patients and chemotherapy regimens are unclear. [ABSTRACT FROM AUTHOR]

Background: Bladder recurrence after radical treatment of upper urinary tract urothelial cancer (UTUC) is frequent, and patients are required to undergo surveillance cystoscopies following surgery. The use of intravesical adjuvant chemotherapy is an accepted method to prevent bladder recurrence, but the timing of this method is not standardized and the concept of intraoperative use is unexplored. Objective: The objective of the study is to examine the feasibility and safety of intraoperative intravesical mitomycin C (MMC) instillation using a closed-circuit system following bladder cuff excision and bladder closure. Design, setting, and participants: All patients who underwent radical nephroureterectomy (RNU) for UTUC at the Department of Urology of Zealand University Hospital, Roskilde, Denmark from 2017 to 2020 were identified. Patient complications within 30 d and data regarding oncological outcome were registered. Outcome measurements and statistical ana lysis: Clavien-Dindo grade for complications and descriptive statistics were used. Results: During the study period, 64 patients underwent RNU. Of these patients, 49 received bladder instillation of MMC during RNU. Complications were observed in 11 patients (21.4%), where four patients (8.2%) had Clavien-Dindo complication grade (CD) I, four patients (8.2%) had CD II, one patient (2%) had CD III, and one patient (2%) had CD IIIa. None of the complications were suspected to be related to MMC. Five of the 15 patients (33%) who did not receive MMC experienced complications. There were no significant differences in complication rates between patients who received MMC and those who did not. Study limitations include a small sample size and a single-center study. Conclusions: Intraoperative vesical instillation of MMC is feasible and was, in the present study, not associated with an increased complication rate. Patient summary: Bladder recurrence after radical treatment of upper urinary tract cancer is frequent. The present study findings indicate that intraoperative bladder irrigation with the chemotherapeutic mitomycin C during surgery does not lead to excessive complications and could be a method to reduce the risk of bladder recurrence.

Purpose: The value of lymphadenectomy during radical nephroureterectomy (RNU) remains unclear. This study aimed to determine the effects of the removed lymph node (RLN) counts, positive lymph node (pLN) counts, and pLN density (pLND) on survival outcomes in patients with node-positive upper urinary tract urothelial cancer (UTUC). Methods: A total of 306 patients with node-positive UTUC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016 were identified. Multivariable Cox regression analyses were used to evaluate the effect of RLN counts, pLN counts, and pLND on survival outcomes. The maximally selected rank statistics were used to determine the most informative cutoff value for pLND on survival outcomes. Results: The RLN counts or pLN counts were not associated with survival outcomes, whereas higher pLND was associated with lower cancer-specific survival (CSS) and overall survival (OS) [hazard ratio (HR) 1.75, P = 0.014 and HR 1.62, P = 0.036, respectively]. The most informative cutoff value for pLND in relation to survival was 27%. Patients with pLND ≥27% had worse 5-year survival rates than those with pLND <27% (52.9% vs. 75.9% for CSS and 18.7% vs. 34.2% for OS, each P < 0.05). Furthermore, the multivariable Cox regression model with pLND could predict 5-year CSS (AUC 0.732 vs. 0.647) or OS (AUC 0.704 vs. 0.621) more accurately than the model without pLND. Conclusions: For patients with node-positive UTUC, more lymph nodes removed do not offer a better therapeutic effect. However, pLND provides additional prognostic value. [ABSTRACT FROM AUTHOR]

Background: The advantage of adjuvant chemotherapy for upper urinary tract urothelial cancer (UTUC) has been reported, whereas its impact on upper tract cancer with variant histology remains unclear. We aimed to answer the abovementioned question with our real-world data. Design, Setting, and Participants: Patients who underwent radical nephroureterectomy (RNU) and were confirmed to have variant UTUC were retrospectively evaluated for eligibility of analysis. In the Taiwan UTUC Collaboration database, we identified 245 patients with variant UTUC among 3,109 patients with UTUC who underwent RNU after excluding patients with missing clinicopathological information. Intervention: Those patients with variant UTUC were grouped based on their history of receiving adjuvant chemotherapy or not. Outcome Measurements and Statistical Analysis: Propensity score matching was used to reduce the treatment assignment bias. Multivariable Cox regression model was used for the analysis of overall, cancer-specific, and disease-free survival. Results and Limitations: For the patients with variant UTUC who underwent adjuvant chemotherapy compared with those without chemotherapy, survival benefit was identified in overall survival in univariate analysis (hazard ratio (HR), 0.527; 95% confidence interval (CI), 0.285–0.973; p = 0.041). In addition, in multivariate analysis, patients with adjuvant chemotherapy demonstrated significant survival benefits in cancer-specific survival (OS; HR, 0.454; CI, 0.208–0.988; p = 0.047), and disease-free survival (DFS; HR, 0.324; 95% CI, 0.155–0.677; (p = 0.003). The main limitations of the current study were its retrospective design and limited case number. Conclusions: Adjuvant chemotherapy following RNU significantly improved cancer-related survivals in patients with UTUC with variant histology. [ABSTRACT FROM AUTHOR]

Abstract Background Selecting the treatment procedure for cancer patients is a challenging task. We report our initial experience of complete laparoscopic radical nephroureterectomy (RNU) for patients with upper urinary tract urothelial cancer (UTUC). Methods A total of four patients with UTUC underwent complete laparoscopic RNU combined with transvesical laparoscopic excision of the distal ureter using three 5-mm ports. Transvaginal specimen extraction was applied in female patients to reduce incisional pain and improve cosmesis. Peri-operative complications were evaluated using the Clavien-Dindo classification system. Postoperative pain was evaluated during hospitalization using a numeric pain rating scale (scales of 1 to 10). Patients who underwent retroperitoneal laparoscopic surgery combined with open excision of the distal ureter during the same period were included as a control group (conventional RNU, consisting of laparoscopic nephrectomy combined with open bladder cuff excision) for pain scale evaluation. Results The novel surgery was successfully completed for all four patients (two males and two females). The mean pneumoperitoneum time for retroperitoneoscopic nephroureterectomy and specimen extraction was 174 min, while the mean pneumovesicum time for the ureteral orifice excision was 88 min. One male patient had bladder leakage at the suture site of the bladder wall, which lasted for 2 weeks. No patient experienced recurrent disease during the follow-up period (median, 10 months). Mild to moderate pain lasted for 5 or 6 days after RNU. A couple of days after surgery, the numeric pain rating scale of complete laparoscopic RNU and conventional RNU group reached its peak level at 3.0 ± 1.8 and 5.3 ± 2.8, respectively. There was no statistical difference in the degree of postoperative pain (P = 0.31). Conclusions We described our initial experience and outcome of complete laparoscopic RNU for UTUC. Further experience and research are required to determine whether this advanced laparoscopic technique yields better outcomes and has true clinical value.

PurposeThe value of lymphadenectomy during radical nephroureterectomy (RNU) remains unclear. This study aimed to determine the effects of the removed lymph node (RLN) counts, positive lymph node (pLN) counts, and pLN density (pLND) on survival outcomes in patients with node-positive upper urinary tract urothelial cancer (UTUC).MethodsA total of 306 patients with node-positive UTUC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016 were identified. Multivariable Cox regression analyses were used to evaluate the effect of RLN counts, pLN counts, and pLND on survival outcomes. The maximally selected rank statistics were used to determine the most informative cutoff value for pLND on survival outcomes.ResultsThe RLN counts or pLN counts were not associated with survival outcomes, whereas higher pLND was associated with lower cancer-specific survival (CSS) and overall survival (OS) [hazard ratio (HR) 1.75, P = 0.014 and HR 1.62, P = 0.036, respectively]. The most informative cutoff value for pLND in relation to survival was 27%. Patients with pLND ≥27% had worse 5-year survival rates than those with pLND

BackgroundThe advantage of adjuvant chemotherapy for upper urinary tract urothelial cancer (UTUC) has been reported, whereas its impact on upper tract cancer with variant histology remains unclear. We aimed to answer the abovementioned question with our real-world data.Design, Setting, and ParticipantsPatients who underwent radical nephroureterectomy (RNU) and were confirmed to have variant UTUC were retrospectively evaluated for eligibility of analysis. In the Taiwan UTUC Collaboration database, we identified 245 patients with variant UTUC among 3,109 patients with UTUC who underwent RNU after excluding patients with missing clinicopathological information.InterventionThose patients with variant UTUC were grouped based on their history of receiving adjuvant chemotherapy or not.Outcome Measurements and Statistical AnalysisPropensity score matching was used to reduce the treatment assignment bias. Multivariable Cox regression model was used for the analysis of overall, cancer-specific, and disease-free survival.Results and LimitationsFor the patients with variant UTUC who underwent adjuvant chemotherapy compared with those without chemotherapy, survival benefit was identified in overall survival in univariate analysis (hazard ratio (HR), 0.527; 95% confidence interval (CI), 0.285–0.973; p = 0.041). In addition, in multivariate analysis, patients with adjuvant chemotherapy demonstrated significant survival benefits in cancer-specific survival (OS; HR, 0.454; CI, 0.208–0.988; p = 0.047), and disease-free survival (DFS; HR, 0.324; 95% CI, 0.155–0.677; (p = 0.003). The main limitations of the current study were its retrospective design and limited case number.ConclusionsAdjuvant chemotherapy following RNU significantly improved cancer-related survivals in patients with UTUC with variant histology.

Abstract Background Whether or not double J (DJ) stenting during transurethral resection of a bladder tumour (TURBT) harms patients with regard to possible metachronous upper urinary tract urothelial cancer (UUTUC) development remains controversial. This study evaluated the impact of DJ compared to nephrostomy placement during TURBT for bladder cancer (BCa) on the incidence of metachronous UUTUCs. Methods We retrospectively analysed 637 patients who underwent TURBT in our department between 2008 and 2016. BCa, UUTUC and urinary drainage data (retrograde/anterograde DJ and percutaneous nephrostomy) were assessed, along with the prevalence of hydronephrosis, and mortality. Chi-square and Fisher’s exact test was performed for univariate analyses. Survival analysis was performed by the Kaplan-Meier method and log-rank tests. Results UUTUC was noted in 28 out of 637 patients (4.4%), whereas only eight (1.3%) developed it metachronously to BCa. Out of these, four patients received DJ stents, while four patients received no urinary drainage of the upper urinary tract. Placement of urinary drainage significantly correlated with UUTUC (50.0% vs. 17.9%; p = 0.041). DJ stenting significantly correlated with UUTUC (50.0% vs. 11%; p

Abstract Background There is growing evidence that the transcription factor nuclear factor E2-related factor 2 (Nrf2) is the major participant in regulating antioxidants and pathways for detoxifying reactive oxygen species (ROS), as well as having a vital role in tumor proliferation, invasion, and chemoresistance. It was also recently reported that Nrf2 supports cell proliferation by promoting metabolic activity. Thus, Nrf2 is involved in progression of cancer. Upper urinary tract urothelial carcinoma (UTUC) is a biologically aggressive tumor with high rates of recurrence and progression, resulting in a poor prognosis. However, the role of Nrf2 in UTUC is largely unknown. Methods In order to study the role of Nrf2 in UTUC from the metabolic perspective, we retrospectively assessed Nrf2 expression in the surgical specimen and the preoperative maximum standard glucose uptake (SUVmax) on [18F]fluorodeoxy-glucose positron emission tomography (18F-FDG-PET) of 107 patients with UTUC who underwent radical nephroureterectomy. Results Increased expression of Nrf2 in the primary lesion was correlated with less differentiated histology, local invasion, and lymph node metastasis, and was also an independent indicator of shorter overall survival according to multivariate analysis. Furthermore, increased expression of Nrf2 was associated with higher preoperative SUVmax by the primary tumor on 18F-FDG-PET, while Nrf2 expression and SUVmax were also significantly correlated in the metastatic lymph nodes. Among the 18 patients with lymph node metastasis at nephroureterectomy who underwent retroperitoneal lymph node dissection and received adjuvant chemotherapy, the patients with higher Nrf2 expression in the primary tumor had worse recurrence-free survival. Conclusions These results suggest that constitutive activation of Nrf2 might be linked with tumor aerobic glycolysis and progression of UTUC, indicating that Nrf2 signaling in the tumor microenvironment promotes progression of UTUC.

Objectives: To investigate the impact on intravesical recurrence and prognosis according to the ureteral ligation timing during radical nephroureterectomy for upper urinary tract urothelial carcinoma. Methods: We carried out a retrospective chart review of 664 patients with non‐metastatic upper urinary tract urothelial carcinoma who underwent radical nephroureterectomy with ureteral ligation (supplementary analysis of JCOG1110A). We excluded patients with previous and/or synchronous bladder cancer, clinically node‐positive disease, no ureteral ligation data, those without ureteral ligation and those with any missing data. We investigated the cumulative incidence of intravesical recurrence and cancer‐specific mortality, and overall survival between patients with ureteral ligation before renovascular ligation (early ureteral ligation), or ureteral ligation after renovascular ligation (late ureteral ligation). Results: Early and late ureteral ligation was carried out in 243 patients (36.6%) and 421 patients (63.4%), respectively. Intravesical recurrence occurred in 218 patients (32.8%) during follow up (median 3.9 years). No significant difference in the intravesical recurrence was found between early and late ureteral ligation groups. Meanwhile, survival in the early ureteral ligation group was significantly worse compared with the late ureteral ligation group. Multivariable analysis showed that early ureteral ligation was an independent prognostic factor for overall survival (hazard ratio 1.88, 95% confidence interval 1.24–2.85, P = 0.003) and cancer‐specific mortality (hazard ratio 1.93, 95% confidence interval 1.14–3.25, P = 0.014). Conclusions: Our findings suggest that the incidence of intravesical recurrence is not affected by the timing of ureteral ligation during radical nephroureterectomy. However, early ureteral ligation might have a negative impact on survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Selecting the treatment procedure for cancer patients is a challenging task. We report our initial experience of complete laparoscopic radical nephroureterectomy (RNU) for patients with upper urinary tract urothelial cancer (UTUC). Methods: A total of four patients with UTUC underwent complete laparoscopic RNU combined with transvesical laparoscopic excision of the distal ureter using three 5-mm ports. Transvaginal specimen extraction was applied in female patients to reduce incisional pain and improve cosmesis. Peri-operative complications were evaluated using the Clavien-Dindo classification system. Postoperative pain was evaluated during hospitalization using a numeric pain rating scale (scales of 1 to 10). Patients who underwent retroperitoneal laparoscopic surgery combined with open excision of the distal ureter during the same period were included as a control group (conventional RNU, consisting of laparoscopic nephrectomy combined with open bladder cuff excision) for pain scale evaluation. Results: The novel surgery was successfully completed for all four patients (two males and two females). The mean pneumoperitoneum time for retroperitoneoscopic nephroureterectomy and specimen extraction was 174 min, while the mean pneumovesicum time for the ureteral orifice excision was 88 min. One male patient had bladder leakage at the suture site of the bladder wall, which lasted for 2 weeks. No patient experienced recurrent disease during the follow-up period (median, 10 months). Mild to moderate pain lasted for 5 or 6 days after RNU. A couple of days after surgery, the numeric pain rating scale of complete laparoscopic RNU and conventional RNU group reached its peak level at 3.0 ± 1.8 and 5.3 ± 2.8, respectively. There was no statistical difference in the degree of postoperative pain (P = 0.31). Conclusions: We described our initial experience and outcome of complete laparoscopic RNU for UTUC. Further experience and research are required to determine whether this advanced laparoscopic technique yields better outcomes and has true clinical value. [ABSTRACT FROM AUTHOR]

Background: Whether or not double J (DJ) stenting during transurethral resection of a bladder tumour (TURBT) harms patients with regard to possible metachronous upper urinary tract urothelial cancer (UUTUC) development remains controversial. This study evaluated the impact of DJ compared to nephrostomy placement during TURBT for bladder cancer (BCa) on the incidence of metachronous UUTUCs.Methods: We retrospectively analysed 637 patients who underwent TURBT in our department between 2008 and 2016. BCa, UUTUC and urinary drainage data (retrograde/anterograde DJ and percutaneous nephrostomy) were assessed, along with the prevalence of hydronephrosis, and mortality. Chi-square and Fisher's exact test was performed for univariate analyses. Survival analysis was performed by the Kaplan-Meier method and log-rank tests.Results: UUTUC was noted in 28 out of 637 patients (4.4%), whereas only eight (1.3%) developed it metachronously to BCa. Out of these, four patients received DJ stents, while four patients received no urinary drainage of the upper urinary tract. Placement of urinary drainage significantly correlated with UUTUC (50.0% vs. 17.9%; p = 0.041). DJ stenting significantly correlated with UUTUC (50.0% vs. 11%; p <  0.01), while no patient with a nephrostomy tube developed UUTUC. UUTUC-free survival rates were significantly lower for patients with DJ stents than for all other patients (p = 0.001). Patients with or without DJ stents had similar overall survival (OS) rates (p = 0.73), whereas patients with nephrostomy tubes had significantly lower OS rates than all other patients (p <  0.001).Conclusions: Patients with DJ stenting during TURBT for BCa might have an increased risk of developing metachronous UUTUC. This study indicated advantages in placing nephrostomy tubes rather than DJ stents; however, confirmation requires investigation of a larger cohort. Even so, the increased mortality rate in the nephrostomy group reflected hydronephrosis as an unfavourable prognostic factor. [ABSTRACT FROM AUTHOR]

Introduction: Non-coding RNAs (ncRNAs) are important regulators of cellular signaling in tumor-related processes. They can not only be detected in tumor tissues, but also in body fluids. ncRNAs are released into circulation as cell-free RNAs in at least two ways: bound to proteins like Ago2 or packed in extracellular vesicles (EV). Therefore, they have a great potential to serve as biomarkers in liquid biopsies. This review gives an overview of the current knowledge concerning ncRNAs and EVs as putative liquid biomarkers in urological tumor diseases. Areas covered: Literature was searched for ncRNAs including microRNA, long non-coding RNA, small interfering RNA, small nuclear RNA, small nucleolar RNA and PIWI-interacting RNA in blood (serum, plasma) and urine samples from urological tumor (urothelial, kidney, prostate, testicular germ cell, penile cancer) patients. Expert opinion: The data demonstrate an important potential of circulating non-coding RNAs as biomarkers in liquid biopsies for diagnosis and follow-up of patients with urological tumors. To translate these markers into clinical practice, independent and prospective validation, standardization of isolation and quantification techniques are inevitable. Another task is the development of predictive ncRNA biomarkers to overcome problems associated with tumor heterogeneity and to select patients individually for systemic therapies. [ABSTRACT FROM AUTHOR]

• Oncologic outcomes following radical nephroureterectomy and segmental ureterectomy (SU) for advanced upper urinary tract urothelial cancer remain poor. • SU is a viable option even in patients with muscle-invasive upper urinary tract urothelial cancer. • Our population-based study suggests that SU provides noninferior cancer-specific survival compared to radical nephroureterectomy. Although kidney-sparing surgery (KSS) is a nonminor option for low-risk upper urinary tract urothelial cancer (UTUC), its oncological benefits in high-risk UTUC remain unclear when compared to radical nephroureterectomy (RNU). This study aimed to compare the oncological outcomes of RNU and KSS in patients with UTUC. We searched the SEER database for patients treated for primary non-metastatic UTUC with either RNU or a kidney-sparing approach (segmental ureterectomy (SU) or local tumor excision (LTE)) between 2004 and 2018. The study included 6,659 patients with primary non-metastatic UTUC treated with surgery; 2,888 (43.4%) and 3,771 (56.6%) patients presented with ureteral and renal pelvicalyceal tumors, respectively. Finally, 5,479 (82.3%) patients underwent RNU, 799 (12.0%) were treated with SU, and 381 (5.7%) patients received LTE. For confounder control, propensity score matching (PSM) of patients treated with SU and RNU was performed to adjust for T stage, grade, age, gender, tumor size, and lymphadenectomy performance. PSM analysis included 694 patients treated with RNU and 694 individuals who underwent SU. In multivariable Cox regression and Kaplan-Meier analyses, we found no difference in either CSS or OS between RNU and SU, even in the subgroup of high-grade and/or muscle-invasive UTUC including pT3-T4 tumors (all p > 0.05). In this population-based study, SU provides equivalent CSS and OS compared to RNU, even in high-risk and locally advanced ureteral cancer. Due to the unavoidable risk of selection bias, further prospective studies are expected to overcome the limitations of this study and support the wider implementation of KSS. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the survival benefits that lymph node dissection (LND) brought to clinically node-negative upper tract urothelial carcinoma (UTUC) patients.Methods: Non-metastatic node-negative UTUC patients were identified from the Surveillance, Epidemiology and End Results database. N0 patients were naturally divided as cN0-pNx group (clinically diagnosed as N0 without LND performed) and cNx-pN0 group (pathologically diagnosed as node-negative no matter what clinical node status they have).Results: Of the 2731 patients included, 2240 and 491 cases were cN0-pNx and cNx-pN0, respectively. The overall survival (OS) of cNx-pN0 patients was significantly better than that of cNx-pN0 patients (p = 0.022). After propensity score matching, the survival of cNx-pN0 patients was still significantly better than cN0-pNx group. Besides, multivariate analyses showed cNx-pN0 (received LND) was an independent favorable prognostic factor for OS and CSS compared with cN0-pNx (no LND). Survival advantages of pN0 group were more significant in ≥ T2 patients and patients with tumor size ≤ 5 cm. Even in N0 patients who received adjuvant treatment, LND still brought obvious survival improvement (HRos = 0.565, p = 0.013; HRcss = 0.607, p = 0.046).Conclusion: LND could improve survival outcomes in patients with clinically node-negative UTUC, especially for those with muscle-invasive diseases (T2-4 stages) or smaller tumor size (≤ 5 cm). Adjuvant treatment after nephroureterectomy is incapable of replacing the therapeutic role of LND. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that the transcription factor nuclear factor E2-related factor 2 (Nrf2) is the major participant in regulating antioxidants and pathways for detoxifying reactive oxygen species (ROS), as well as having a vital role in tumor proliferation, invasion, and chemoresistance. It was also recently reported that Nrf2 supports cell proliferation by promoting metabolic activity. Thus, Nrf2 is involved in progression of cancer. Upper urinary tract urothelial carcinoma (UTUC) is a biologically aggressive tumor with high rates of recurrence and progression, resulting in a poor prognosis. However, the role of Nrf2 in UTUC is largely unknown.Methods: In order to study the role of Nrf2 in UTUC from the metabolic perspective, we retrospectively assessed Nrf2 expression in the surgical specimen and the preoperative maximum standard glucose uptake (SUVmax) on [18F]fluorodeoxy-glucose positron emission tomography (18F-FDG-PET) of 107 patients with UTUC who underwent radical nephroureterectomy.Results: Increased expression of Nrf2 in the primary lesion was correlated with less differentiated histology, local invasion, and lymph node metastasis, and was also an independent indicator of shorter overall survival according to multivariate analysis. Furthermore, increased expression of Nrf2 was associated with higher preoperative SUVmax by the primary tumor on 18F-FDG-PET, while Nrf2 expression and SUVmax were also significantly correlated in the metastatic lymph nodes. Among the 18 patients with lymph node metastasis at nephroureterectomy who underwent retroperitoneal lymph node dissection and received adjuvant chemotherapy, the patients with higher Nrf2 expression in the primary tumor had worse recurrence-free survival.Conclusions: These results suggest that constitutive activation of Nrf2 might be linked with tumor aerobic glycolysis and progression of UTUC, indicating that Nrf2 signaling in the tumor microenvironment promotes progression of UTUC. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of lymph node dissection (LND) on clinical outcome during radical nephroureterectomy (RNU) for patients with upper urinary tract urothelial cancer (UTUC). Methods: We, the Urologic Oncology Study Group of the Japan Clinical Oncology Group (JCOG), retrospectively collected data from patients with non-metastatic UTUC who underwent RNU in 30 centers in 1995-2009. Ineligible patients and patients with previous and/or synchronous bladder cancer were excluded, and the remaining 2037 patients were analyzed. We compared overall and cancer-specific mortality between patients who underwent LND (LND group) and those without LND (no-LND group). Results: Among 2037 patients, LND was performed in 1046 (51.4%) patients, and 223 (10.9%) patients had pathological node-positive (pN+) disease. All-cause mortality was observed in 503 patients (24.7%) during follow-up (median 45.8 months), including 363 patients (17.8%) who died of UTUC. Patients with pN+ disease showed significantly shorter overall survival (OS) compared with pN0 patients, and the estimated 5-year OS for pN+ patients was 30%. Older age, ≥cT3, and clinical node-positive disease were found as preoperative predictors for pN+ disease by multivariate analysis. In the comparison of OS and cancer-specific mortality between LND and no-LND groups, there was no significant improvement by LND in multivariate analysis. The median number of lymph nodes removed was six (IQR 3-11). There was no significant association between the number of lymph nodes removed and OS. Conclusions: The present study indicates that there is no therapeutic benefit of LND during RNU for UTUC, although pathologically positive LN status can predict poor prognosis. [ABSTRACT FROM AUTHOR]

Objectives To describe the nature of metastatic upper urinary tract urothelial cancer and determine the prognostic predictors or treatment modality associated with all-cause mortality. Methods Within the nationwide case series study of the Japanese Urological Association, consisting of 1509 patients with urinary tract urothelial cancer diagnosed in 2005, we identified 102 patients with metastatic urinary tract urothelial cancer. Univariate and multivariate survival analyses identified prognostic outcome variables. Results Predominant sites of distant metastasis at diagnosis were the lungs (54.9%), distant lymph nodes (37.3%), bone (32.4%) and liver (19.6%). Of 102 patients, 70 patients (68.6%) died during the median follow-up period of 6 months, and the 2-year overall survival rate was estimated at 22%. The median survival time to all-cause mortality was 8.5 months (95% confidence interval 6.4-10.7 months). On multivariate analysis, independent predictive factors for all-cause mortality were age (hazard ratio 2.36, P = 0.015) and liver metastasis (hazard ratio 2.35, P = 0.037). Patients who received multimodal treatment including chemotherapy and surgery showed significantly better prognosis (median survival time 25.8 months) compared with patients treated with chemotherapy alone (median survival time 7.3 months) or best supportive care (median survival time 4.3 months). Conclusions Age at diagnosis and the presence of liver metastasis seem to have an impact on survival of metastatic urinary tract urothelial cancer patients. Multimodal treatment including systemic chemotherapy and surgery might result in better prognosis in some of these patients. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? Open radical nephroureterectomy ( ORNU) with excision of the ipsilateral bladder cuff is a standard treatment for upper tract urothelial carcinoma ( UTUC). However, over the past decade laparoscopic RNU ( LRNU) has emerged as a minimally invasive surgical alternative. Data comparing the oncological efficacy of ORNU and LRNU have reported mixed results and the equivalence of these surgical techniques have not yet been established., We found that surgical approach was not independently associated with overall or disease-specific survival; however, there was a trend toward an independent association between LRNU and poorer recurrence-free survival ( RFS). To our knowledge, this is the first large, multi-institutional analysis to show a trend toward inferior RFS in patients with UTUC treated with LRNU., Objective To examine the association between surgical approach for radical nephroureterectomy ( RNU) and clinical outcomes in a large, multi-institutional cohort, as there are limited data comparing the oncological efficacy of open RNU ( ORNU) and laparoscopic RNU ( LRNU) for upper urinary tract urothelial carcinoma ( UTUC)., Patients and Methods Institutional RNU databases containing detailed information on patients with UTUC treated between 1994 and 2009 were obtained from 10 academic centres in Canada., Data were collected on 1029 patients and combined into a relational database formatted with patient characteristics, pathological characteristics, and survival status., Surgical approach was classified as ORNU ( n = 403) or LRNU ( n = 446)., The clinical outcomes were overall survival ( OS), disease-specific survival ( DSS), and recurrence-free survival ( RFS). The Kaplan-Meier method and Cox proportional regression analysis were used to analyse survival data., Results Data were evaluable for 849 of 1029 (82.5%) patients., The median (interquartile range) follow-up duration was 2.2 (0.6-5.0) years., The predicted 5-year OS (67% vs 68%, log-rank P = 0.19) and DSS (73% vs 76%, log-rank P = 0.32) rates did not differ between the ORNU and LRNU groups; however, there was a trend toward an improved predicted 5-year RFS rate in the ORNU group (43% vs 33%, log-rank P = 0.06)., Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with OS (hazard ratio [ HR] 0.89, 95% confidence interval [ CI] 0.63-1.27, P = 0.52) or DSS ( HR 0.90, 95% CI 0.60-1.37, P = 0.64); however, there was a trend toward an independent association between surgical approach and RFS ( HR 1.24, 95% CI 0.98-1.57, P = 0.08)., Conclusion Surgical approach was not independently associated with OS or DSS but there was a trend toward an independent association between LRNU and poorer RFS. Further prospective evaluation is needed. [ABSTRACT FROM AUTHOR]

Upper tract urothelial cancer (UTUC) accounts for roughly 5 % of all urothelial cancers. At presentation, 30 % of patients demonstrate invasive and/or locally advanced disease, 30-40 % have regional lymph node involvement, and 20 % harbor metastatic disease. Systemic recurrence and progression rates after surgery for patients with advanced disease range between 45-60 %. Five-year cancer specific survival rates for pT2 and pT3 tumors are 73 % and 40 %, respectively. Median survival for patients with pT4 disease is approximately 6 months. Nonetheless, there is a lack of improvement in the rates of systemic recurrence and progression in patients with advanced UTUC. Extrapolating evidence obtained from experience with multi-modal therapy of patients with urothelial bladder cancer, additional improvements in oncological outcomes for patients with UTUC can be achieved through integration of effective systemic chemotherapy with local tumor control. We provide an overview of the rationale and utilization strategies of peri-operative systemic chemotherapy in patients with UTUC. [ABSTRACT FROM AUTHOR]

OBJECTIVE To compare the oncological outcomes of laparoscopic radical nephroureterectomy (LNU) vs open NU (ONU) for upper urinary tract transitional cell carcinoma (TCC). PATIENTS AND METHODS Between July 1999 and January 2003, we performed 70 LNUs and 70 ONUs for TCC of the upper urinary tract. ONU was reserved for patients with previous abdominal surgery or with severe cardiac and/or pulmonary problems. Demographic data, tumour staging and histological grading and rates of metastasis were recorded and compared. RESULTS For LNU and ONU the mean operative durations were 240 min and 190 min, respectively. The definitive pathology showed a high incidence of tumour stage pT2 G2 in both LNU and ONU groups. The median follow-up was 60 months. In the LNU group, the 5-year disease-free survival (DFS) was 75%: 100% for pTa, 88% for pT1, 78% for pT2, and 35% for pT3 ( P < 0.001). In the ONU group, the 5-year DFS was 73% (LNU vs ONU, P = 0.037): 100% for pTa, 89% for pT1, 75% for pT2 and 31% for pT3 ( P < 0.001). CONCLUSION The results of our long-term controlled study support the use of LNU as an effective alternative to ONU in the therapy of upper urinary tract urothelial cancer. [ABSTRACT FROM AUTHOR]

OBJECTIVES To clarify the significance of lymphovascular invasion (LVI) in patients with pT3N0M0 upper urinary tract (UUT) urothelial carcinoma (UC) relative to prognosis in terms of disease-specific survival, as LVI, which implies both blood vessel and lymph vessel involvement, is reportedly a poor prognostic factor in patients with UUT-UC. PATIENTS AND METHODS The clinical records of 90 patients who had surgery for UUT-UC were reviewed retrospectively. The median patient age was 71 years and the median follow-up was 42 months. The prognostic significances of LVI (with vs without), T stage (<1 vs 2–4), grade (1–2 vs 3), N stage (0 vs 1–2), age (≤70 vs >70 years), gender and tumour location (renal pelvis vs ureter) for survival time were evaluated. RESULTS LVI of UUT-UC was found in 34 patients (37.8%). There were significantly higher frequencies of LVI with advancing stage and lymph node metastasis. Kaplan-Meier analysis showed that LVI was strongly associated with disease-specific survival in all patients ( P < 0.001) and in patients with pT3N0M0 disease ( P < 0.001). Univariate analyses showed that LVI, T stage, N stage and tumour grade were significantly related to disease-specific survival in all patients ( P < 0.001, <0.001, 0.003 and 0.007, respectively). Multivariate analysis using Cox proportional hazards model showed that LVI was the only prognostic factor with independent significance for disease-specific survival ( P < 0.001). CONCLUSIONS LVI appears to be an important and independent prognostic factor for UUT-UC in patients treated by nephroureterectomy. Our data suggest that the LVI status might be a predictive marker for disease-specific survival in patients with T3N0M0 UTT-UC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of lymph node dissection (LND) on the clinical outcomes during radical nephroureterectomy (RNU) in patients with clinically node-negative upper urinary tract urothelial cancer (UTUC)., Methods: Within the nationwide case series of the Japanese Urological Association, which comprises 1509 patients with UTUC diagnosed in 2005, we identified 823 patients with clinically node-negative UTUC who underwent RNU. The extent of limited LND was defined as the renal hilar region only for renal pelvic cancer and as either the pelvic region or para-aortic/paracaval region only for ureteral cancer, while the extent of wider LND was defined as at least one perilesional LND region in addition to limited LND. Multivariate analysis with a Cox regression hazard model was used to evaluate the survival benefit., Results: Among the 823 patients, LND was performed in 197 (23.9%) patients, and 26 (13.2%) of them had pathologically node-positive disease. Of 197 patients who underwent LND, limited and wider LND was performed in 119 (60.4%) and 78 (39.6%) patients, respectively. Patients with node-positive disease showed significantly shorter overall survival than those with node-negative disease. No LND-associated survival improvement was observed in a direct comparison between patients with and without LND. In addition, limited or wider LND was not associated with overall survival or cancer-specific survival., Conclusions: The therapeutic benefit obtained by LND remains unclear regardless of the extent of LND, although LND has diagnostic value with respect to the prediction of a poor prognosis especially in patients with clinically muscle-invasive disease., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)