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Objectives: To evaluate the predictive role of pre-nephroureterectomy (NU) hydronephrosis on post-NU renal function (RF) change and preserved eligibility rate for adjuvant therapy in patients with upper tract urothelial carcinoma (UTUC)., Patients and Methods: This retrospective study collected data of 1018 patients from the Taiwan UTUC Collaboration Group registry of 26 institutions. The patients were divided into two groups based on the absence or presence of pre-NU hydronephrosis. Estimated glomerular filtration rate (eGFR) was calculated pre- and post-NU respectively. The one month post-NU RF change, chronic kidney disease (CKD) progression, and the preserved eligibility rate for adjuvant therapy were compared for each CKD stage., Results: 404 (39.2%) patients without and 614 (60.8%) patients with pre-NU hydronephrosis were enrolled. The median post-NU change in the eGFR was significantly lower in the hydronephrosis group (-3.84 versus -12.88, p<0.001). Pre-NU hydronephrosis was associated with a lower post-NU CKD progression rate (33.1% versus 50.7%, p < 0.001) and was an independent protective factor for RF decline after covariate adjustment (OR=0.46, p <0.001). Patients with pre-NU hydronephrosis had a higher preserved eligibility rate for either adjuvant cisplatin-based chemotherapy (OR=3.09, 95%CI 1.95-4.69) or immune-oncology therapy (OR=2.31, 95%CI 1.23-4.34)., Conclusion: Pre-NU hydronephrosis is an independent protective predictor for post-NU RF decline, CKD progression, and eligibility for adjuvant therapy. With cautious selection for those unfavorably prognostic, non-metastatic UTUC patients with preoperative hydronephrosis, adjuvant rather than neoadjuvant therapy could be considered due to higher chance of preserving eligibility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cheng, Lee, Li, Huang, Liu, Chen, Lin, Lo, Yu, Wang, Chen, Tseng, Lin, Yeong-Chin, Cheong, Jiang, Lee, Chen, Chen, Chiang, Hsueh, Huang, Wu, Lin, Tsai, Yu, Huang, Huang and Tsai.)

Purpose: This study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU)., Methods: In this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (>90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan-Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression., Results: Of the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166-3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137-3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival., Conclusions: For patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Chang, Wu, Huang, Liu, Yang, Li, Tseng, Lin, Yu, Lo, Huang, Chen, Tsai, Cheng, Jiang, Lee, Chen, Yeh, Lin, Tsai, Hsueh, Chiang, Chiang, Lin, Jou, Pang and Ke.)

Purpose: We aimed to evaluate the impact of preoperative local symptoms on prognosis after radical nephroureterectomy in patients with upper tract urothelial carcinoma (UTUC)., Methods: This retrospective study consisted of 2,662 UTUC patients treated at 15 institutions in Taiwan from 1988 to 2019. Clinicopathological data were retrospectively collected for analysis by the Taiwan UTUC Collaboration Group. The Kaplan-Meier method was used to calculate overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS). The prognostic value of preoperative local symptoms in OS, CSS, DFS, and BRFS was investigated using Cox proportional hazards models., Results: The median follow-up was 36.6 months. Among 2,662 patients, 2,130 (80.0%) presented with hematuria and 398 (15.0%) had symptomatic hydronephrosis at diagnosis. Hematuria was associated with less symptomatic hydronephrosis ( p < 0.001), more dialysis status ( p = 0.027), renal pelvic tumors ( p < 0.001), and early pathological tumor stage ( p = 0.001). Symptomatic hydronephrosis was associated with female patients ( p < 0.001), less dialysis status ( p = 0.001), less bladder cancer history ( p < 0.001), ureteral tumors ( p < 0.001), open surgery ( p = 0.006), advanced pathological tumor stage ( p < 0.001), and postoperative chemotherapy ( p = 0.029). Kaplan-Meier analysis showed that patients with hematuria or without symptomatic hydronephrosis had significantly higher rates of OS, CSS, and DFS (all p < 0.001). Multivariate analysis confirmed that presence of hematuria was independently associated with better OS (HR 0.789, 95% CI 0.661-0.942) and CSS (HR 0.772, 95% CI 0.607-0.980), while symptomatic hydronephrosis was a significant prognostic factor for poorer OS (HR 1.387, 95% CI 1.142-1.683), CSS (HR 1.587, 95% CI 1.229-2.050), and DFS (HR 1.378, 95% CI 1.122-1.693)., Conclusions: Preoperative local symptoms were significantly associated with oncological outcomes, whereas symptomatic hydronephrosis and hematuria had opposite prognostic effects. Preoperative symptoms may provide additional information on risk stratification and perioperative treatment selection for patients with UTUC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yeh, Chang, Fang, Chen, Lin, Hong, Huang, Wang, Chen, Lo, Yu, Tseng, Lin, Jou, Cheong, Jiang, Tsai, Hsueh, Chen, Huang, Tsai, Lin, Wu, Lin, Lin and Wu.)

Purpose: This study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) during radical nephroureterectomy (NU)., Methods: From the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan-Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (-) groups., Results: A total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients., Conclusions: We found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Chang, Huang, Yu, Lo, Chung, Wu, Chen, Lin, Jiang, Lee, Hsueh, Chiu, Chen, Lin, Tsai, Chen, Chiang, Huang, Chen, Huang, Wu, Lin, Tseng, Ke and Yeh.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lo, Li, Ke, Chang, Wu, Chen, Lin, Huang, Chen, Tseng, Lin, Jiang, Lee, Tsai, Chung, Hsueh, Chiu, Jou, Cheong, Chen, Chen, Chiang, Yu, Lin, Wu, Chen, Weng and Tsai.)

Background: Taiwan is one of the endemic regions where upper tract urothelial carcinoma (UTUC) accounts for approximately a third of all urothelial tumors. Owing to its high prevalence, extensive experience has been accumulated in minimally invasive radical nephroureterectomy (RNU). Although a variety of predictive factors have been explored in numerous studies, most of them were on a single-center or limited institutional basis and data from a domestic cohort are lacking., Objective: This study aims to identify significant predicting factors of oncological outcomes, including overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and intravesical recurrence-free survival (IVRFS), following RNU for UTUC in Taiwan., Methods: A multicenter registry database, Taiwan UTUC Collaboration Group, was utilized to analyze oncological outcomes of 3,333 patients undergoing RNU from 1988 to 2021 among various hospitals in Taiwan. Clinicopathological parameters were recorded according to the principles established by consensus meetings. The Kaplan-Meier estimator was utilized to estimate the survival rates, and the curves were compared using the stratified log-rank test. Univariate and multivariate analyses were performed with the Cox proportional hazard model to explore potential predicting factors., Results: With a median follow-up of 41.8 months in 1,808 patients with complete information, the 5-year IVRFS, DFS, CSS, and OS probabilities were 66%, 72%, 81%, and 70%, respectively. In total, 482 patients experienced intravesical recurrence, 307 died of UTUC, and 583 died of any cause. Gender predominance was female (57%). A total of 1,531 patients (84.7%) had high-grade tumors; preoperative hydronephrosis presented in 1,094 patients (60.5%). Synchronous bladder UC was identified in 292 patients (16.2%). Minimally invasive procedures accounted for 78.8% of all surgeries, including 768 hand-assisted laparoscopic (42.5%) and 494 laparoscopic (27.3%) approaches. Synchronous bladder UC was the dominant adverse predicting factor for all survival outcomes. Other independent predicting factors for OS, CSS, and DFS included age ≧70, presence of preoperative hydronephrosis, positive surgical margin, LVI, pathological T and N staging, and laparoscopic RNU., Conclusion: Synchronous UC of the urinary bladder is an independent adverse prognostic factor for survival in UTUC. The presence of preoperative hydronephrosis was also corroborated as a disadvantageous prognostic factor. Our multivariate analysis suggested that laparoscopic RNU might provide better oncological control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Chang, Huang, Wu, Li, Chen, Huang, Lo, Yu, Tsai, Wu, Tseng, Lin, Jiang, Lee, Jou, Cheong, Hsueh, Chiu, Chen, Chen, Chiang, Tsai, Lin, Wu, Lin and Yu.)

Purpose: This study aimed to compare the oncological outcomes and surgical complications of patients with upper tract urothelial carcinoma (UTUC) treated with different minimally invasive techniques for nephroureterectomy., Methods: From the updated data of the Taiwan UTUC Collaboration Group, a total of 3,333 UTUC patients were identified. After excluding ineligible cases, we retrospectively included 1,340 patients from 15 institutions who received hand-assisted laparoscopic nephroureterectomy (HALNU), laparoscopic nephroureterectomy (LNU) or robotic nephroureterectomy (RNU) between 2001 and 2021. Kaplan-Meier estimator and Cox proportional hazards model were used to analyze the survival outcomes, and binary logistic regression model was selected to compare the risks of postoperative complications of different surgical approaches., Results: Among the enrolled patients, 741, 458 and 141 patients received HALNU, LNU and RNU, respectively. Compared with RNU (41.1%) and LNU (32.5%), the rate of lymph node dissection in HALNU was the lowest (17.4%). In both Kaplan-Meier and univariate analysis, the type of surgery was significantly associated with overall and cancer-specific survival. The statistical significance of surgical methods on survival outcomes remained in multivariate analysis, where patients undergoing HALNU appeared to have the worst overall (p = 0.007) and cancer-specific (p = 0.047) survival rates among the three groups. In all analyses, the surgical approach was not related to bladder recurrence. In addition, HALNU was significantly associated with longer hospital stay (p = 0.002), and had the highest risk of major Clavien-Dindo complications (p = 0.011), paralytic ileus (p = 0.012), and postoperative end-stage renal disease (p <0.001)., Conclusions: Minimally invasive surgery can be safe and feasible. We proved that compared with the HALNU group, the LNU and RNU groups have better survival rates and fewer surgical complications. It is crucial to uphold strict oncological principles with sophisticated technique to improve outcomes. Further prospective studies are needed to validate our findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Chang, Huang, Hong, Huang, Chen, Lin, Lo, Yu, Tseng, Lin, Wu, Chung, Hsueh, Chiu, Chen, Chen, Jiang, Tsai, Chiang, Lin, Jou, Wu, Lee and Yeh.)