The clinical impact of ureteroscopy for upper tract urothelial carcinoma: A multicenter study.

BACKGROUND: With the development of kidney-sparing surgery and neoadjuvant chemotherapy, ureteroscopic biopsy (URSBx) has become important for the management of upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analyzed data from 744 patients with UTUC who underwent radical nephroureterectomy (RNU), stratified into no ureteroscopy (URS), URS alone, and URSBx groups. Intravesical recurrence-free survival (IVRFS) was examined using the Kaplan-Meier method. We conducted Cox regression analyses to identify risk factors for IVR. We investigated differences between clinical and pathological staging to assess the ability to predict the pathological tumor stage and grade of RNU specimens. RESULTS: Kaplan-Meier curves and multivariate Cox regression revealed significantly more IVR and inferior IVRFS in patients who underwent URS and URSBx. Superficial, but not invasive, bladder cancer recurrence was more frequent in the URS and URSBx groups than in the no URS group. Clinical and pathological staging agreed for 55 (32.4%) patients. Downstaging occurred for 48 (28.2%) patients and clinical understaging occurred for 67 (39.4%) patients. Upstaging to muscle-invasive disease occurred for 39 (35.8%) of 109 patients with ≤cT1 disease. Clinical and pathological grading were similar for 72 (42.3%) patients. Downgrading occurred for 5 (2.9%) patients, and clinical undergrading occurred for 93 (54.7%) patients. CONCLUSION: URS and URSBx instrumentation will be risk factors for superficial, but not invasive, bladder cancer recurrence. Clinical understaging/undergrading and upstaging to muscle-invasive disease occurred for a large proportion of patients with UTUC who underwent RNU. These data emphasize the challenges involved in accurate UTUC staging and grading.

Variant histology is associated with more non-urothelial tract recurrence but less intravesical recurrence for upper tract urothelial carcinoma after radical nephroureterectomy.

PURPOSE: To investigate the prognostic impact of variant histology (VH) on oncological outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) who had undergone radical nephroureterectomy (RNU). PATIENTS AND METHODS: A total of 1239 patients with clinically localized UTUC who underwent RNU at a single institution between January 2005 and June 2020 were included. The VH was reviewed by a uro-pathologist at our institution. The Cox regression model was used to perform multivariate analysis, including VH and other established prognostic factors for post-RNU oncological outcomes (intravesical recurrence [IVR], non-urothelial recurrence, and cancer-specific death). RESULTS: Of the 1239 patients with UTUC, 384 patients (31%) were found to have VH. Advanced tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, open surgery, and renal pelvis had a significantly larger proportion of UTUC with VH compared to pure UTUC (all p < 0.05). VH was an independent prognostic factor associated with less IVR identified by multivariate analysis, more non-urothelial recurrence, and more cancer-specific mortality. CONCLUSION: Patients with VH account for 31% with UTUC treated with RNU in this cohort. VH was an independent prognostic factor associated with more non-urothelial recurrence and cancer-specific mortality but less IVR.

Clinical features and oncological outcomes of bladder cancer microsatellite instability.

OBJECTIVES: Excellent anticancer effect for solid tumors with microsatellite instability (MSI)-high by anti-PD-1 antibody has been reported. In this study, we investigated the clinical impact of MSI status in bladder cancer. METHODS: This study included 205 Japanese patients who underwent transurethral resection for bladder cancer between 2005 and 2021. The prevalence rates of microsatellite stable (MSS), MSI-low (MSI-L), and MSI-high (MSI-H) were determined using molecular testing. We examined the association of MSI status (MSS versus MSI-L/H) with clinicopathological characteristics and oncological outcomes. RESULTS: MSI-L/H tumors were associated with higher T-category in non-muscle invasive bladder cancer (NMIBC). Additionally, MSI-L/H tumors were associated with a higher risk of intravesical recurrence in NMIBC patients treated with intravesical bacillus Calmette-Guérin (BCG) but not with non-BCG therapy. CONCLUSIONS: This study suggested that the MSI status might serve as a predictive marker for intravesical recurrence after BCG intravesical therapy in NMIBC and highlighted an unmet need for an alternative treatment in patients with MSI-L/H tumors.

Photodynamic diagnosis-assisted transurethral resection of bladder tumor for high-risk non-muscle invasive bladder cancer improves intravesical recurrence-free survival (BRIGHT study).

OBJECTIVES: In a primary analysis of data from the BRIGHT study (UMIN000035712), photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) using oral 5-aminolevulinic acid hydrochloride reduced residual tumors in high-risk non-muscle invasive bladder cancer (NMIBC). We aimed to evaluate the effectiveness of PDD-TURBT for intravesical recurrence after a second transurethral resection for high-risk NMIBC. METHODS: High-risk NMIBC patients initially treated with PDD-TURBT (PDD group) were prospectively registered between 2018 and 2020. High-risk patients with NMIBC who were initially treated with white-light TURBT (WL group) were retrospectively registered. Intravesical recurrence-free survival after the second transurethral resection was compared between the PDD and WL groups using propensity score matching analysis. RESULTS: In total, 177 patients were enrolled in the PDD group, and 306 patients were registered in the WL group. After propensity score matching (146 cases in each group), intravesical recurrence within 1 year was significantly less frequent in the PDD group than in the WL group (p = 0.004; hazard ratio [HR] 0.44, 95% confidence interval [CI]: 0.25-0.77). In subgroup analysis, PDD-TURBT showed a particularly high efficacy in reducing intravesical recurrence within 1 year, especially in cases of tumors measuring less than 3 cm (p = 0.003; HR 0.31, 95% CI: 0.14-0.67), absence of residual tumor at second transurethral resection (p = 0.020; HR 0.37, 95% CI: 0.16-0.86), and no postoperative intravesical Bacillus Calmette-Guérin therapy (p < 0.001; HR 0.27, 95% CI: 0.13-0.58). CONCLUSIONS: PDD-TURBT may reduce short-term intravesical recurrence in patients with high-risk NMIBC.

A 6-month maintenance schedule of mitomycin C after radical nephroureterectomy for upper tract urothelial carcinoma for the prevention of intravesical recurrence: a retrospective, single center study.

PURPOSE: To show the effect of a 6-month (4 times weekly followed by 5 times monthly) maintenance mitomycin C regimen on the prevention of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: A total of 119 patients undergoing a RNU between 2007 and 2021 in a single center hospital were retrospectively reviewed. A total of 66 patients were eligible for further analysis. 27 patients received no post-operative MMC (median follow-up: 110 months) and 39 patients received a 6-month (4 times weekly, 5 times monthly) maintenance regimen of MMC (median follow up: 48 months). The primary outcome was the 1-, 2- and 5-year bladder recurrence free survival (BRFS). RESULTS: There was a significant difference (p = 0.001) in BRFS between the two groups. The 1-, 2, and 5-year BRFS for the MMC- group was 67%, 63% and 43%, respectively. The 1-, 2- and 5-year BRFS for the MMC + group was 95%, 86% and 86%, respectively. Univariate analysis showed no other potential prognostic factors that had a significant effect on the BRFS. CONCLUSION: A 6-month maintenance schedule of MMC is effective at significantly reducing the risk of IVR after RNU for UTUC. We could not find any other significant prognostic factors to predict IVR.

The Japanese health care system-based cost-effectiveness of photodynamic diagnosis-assisted transurethral resection of bladder tumor for non-muscle invasive bladder cancer.

BACKGROUND: Photodynamic diagnosis-assisted transurethral resection of bladder tumor reduces the risk of intravesical recurrence compared with conventional white light-transurethral resection of bladder tumor. However, the patient burden of costs for photodynamic diagnosis-transurethral resection of bladder tumor is higher than that for white light-transurethral resection of bladder tumor per installment, and the impact of the medical economics of photodynamic diagnosis-transurethral resection of bladder tumor is unclear. Therefore, we evaluated the Japanese health care system-based cost-effectiveness of photodynamic diagnosis-transurethral resection of bladder tumor compared with that of white light-transurethral resection of bladder tumor. METHODS: We conducted a retrospective chart review of 100 patients who underwent initial white light- or photodynamic diagnosis-transurethral resection of bladder tumor for non-muscle invasive bladder cancer from February 2012 to August 2019. Cumulative intravesical recurrences during 1000 post-operative days after the initial transurethral resection of bladder tumor were counted. Furthermore, the cumulative costs were calculated using the Diagnostic Procedure Combination and Per-Diem Payment System unique to Japan. The costs/year/person calculated using the person-year method was compared between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor. RESULTS: Among the 100 patients, 40 (40%) and 60 (60%) underwent the initial white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The cumulative incidence of bladder recurrence requiring hospitalization and transurethral resection of bladder tumor was 20 and 5% for the white light-transurethral resection of bladder tumor and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The costs for hospitalization and surgical procedures per white light- or photodynamic diagnosis-transurethral resection of bladder tumor were 348 228 and 481 820 Japanese yen, respectively. The cost/year/person by the person-year method was 8073 and 8557 Japanese yen for the white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. CONCLUSIONS: The cost/year/person for hospitalization and surgical procedures was slightly different between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor. Furthermore, photodynamic diagnosis-transurethral resection of bladder tumor can reduce intravesical recurrence and is more cost-effective than white light-transurethral resection of bladder tumor.

Patients with Non-Muscle-Invasive Bladder Cancer Previously Treated with Nephroureterectomy Have a High Risk of Recurrence after Bacillus Calmette-Guérin Intravesical Instillation Therapy.

BACKGROUND: There is a high incidence of intravesical recurrence after transurethral resection of bladder tumor for non-muscle-invasive bladder cancer (NMIBC). Intravesical instillation of bacillus Calmette-Guérin (BCG) is widely used to prevent recurrence and progression. There are two types of NMIBC: primary NMIBC and subsequent NMIBC after radical nephroureterectomy (RNU). We compared the clinical outcomes of BCG intravesical instillation therapy between the two types of NMIBC. PATIENTS AND METHODS: This study included a total of 357 patients, who received BCG intravesical instillation therapy to prevent recurrence of NMIBC (pTa/pT1) between 1991 and 2019. Among them, 34 patients had subsequent NMIBC after RNU, and the remaining 323 patients had primary NMIBC. This retrospective study analyzed 68 patients extracted by propensity score matching. Survival curves were estimated using the Kaplan-Meier method, and independent prognostic factors for survival were examined by the Cox proportional hazards model. RESULTS: The 3-year recurrence-free survival (RFS) rates in patients with primary NMIBC and subsequent NMIBC after RNU were 70.7% and 54.8%, respectively (p = 0.036). However, there were no significant differences between the two groups in progression-free survival and cancer-specific survival. Multivariate analysis of RFS showed that only a previous history of upper tract urothelial carcinoma was an independent prognostic and predictive factor. CONCLUSION: Patients with subsequent NMIBC after RNU treated with BCG intravesical instillation therapy have a higher risk of recurrence than those with primary NMIBC. Thus, stringent follow-up is necessary for patients with subsequent NMIBC after RNU.

Impact of previous malignancy at diagnosis on oncological outcomes of upper tract urothelial carcinoma.

BACKGROUND: The evidence of prognostic factors and individualized surveillance strategies for upper tract urothelial carcinoma are still weak. OBJECTIVES: To evaluate whether the history of previous malignancy (HPM) affects the oncological outcomes of upper tract urothelial carcinoma (UTUC). METHODS: The CROES-UTUC registry is an international, observational, multicenter cohort study on patients diagnosed with UTUC. Patient and disease characteristics from 2380 patients with UTUC were collected. The primary outcome of this study was recurrence-free survival. Kaplan-Meier and multivariate Cox regression analyses were performed by stratifying patients according to their HPM. RESULTS: A total of 996 patients were included in this study. With a median recurrence-free survival time of 7.2 months and a median follow-up time of 9.2 months, 19.5% of patients had disease recurrence. The recurrence-free survival rate in the HPM group was 75.7%, which was significantly lower than non-HPM group (82.7%, P = 0.012). Kaplan-Meier analyses also showed that HPM could increase the risk of upper tract recurrence (P = 0.048). Furthermore, patients with a history of non-urothelial cancers had a higher risk of intravesical recurrence (P = 0.003), and patients with a history of urothelial cancers had a higher risk of upper tract recurrence (P = 0.015). Upon multivariate Cox regression analysis, the history of non-urothelial cancer was a risk factor for intravesical recurrence (P = 0.004), and the history of urothelial cancer was a risk factor for upper tract recurrence (P = 0.006). CONCLUSION: Both previous non-urothelial and urothelial malignancy could increase the risk of tumor recurrence. But different cancer types may increase different sites' risk of tumor recurrence for patients with UTUC. According to present study, more personalized follow-up plans and active treatment strategies should be considered for UTUC patients.

Preoperative risk classification for intravesical recurrence after laparoscopic radical nephroureterectomy for upper tract urothelial carcinoma in a multi-institutional cohort.

INTRODUCTION: This study aimed to identify preoperative risk factors and create a risk classification for intravesical recurrence of upper urinary tract urothelial carcinoma only after laparoscopic radical nephroureterectomy in a multi-institutional cohort. METHODS: We retrospectively analyzed 283 patients who had undergone laparoscopic radical nephroureterectomy for nonmetastatic upper tract urothelial cancer between March 2002 and March 2020. The cumulative incidence of intravesical recurrence for 224 patients without previous or concomitant bladder cancer was examined using multivariate Fine-Gray competing risks proportional hazards models. A risk stratification model was created to predict subsequent patient outcomes based on the results. RESULTS: The median follow-up duration was 33.3 months, and 71 (31.7%) patients experienced intravesical recurrence. The estimated cumulative incidence of intravesical recurrence at one and 5 years was 23.5% and 36.4%, respectively. In multivariate analysis, the presence of ureter tumors and multiple tumors were shown to be independently significant predictive factors for intravesical recurrence. Based on the results, we classified patients into three risk groups. The cumulative incidence rates of intravesical recurrence within 5 years after surgery were 24.4%, 42.5%, and 66.7% in the low-, intermediate-, and high-risk groups, respectively. CONCLUSIONS: We identified risk factors and created a risk classification model for intravesical recurrence of upper urinary tract urothelial carcinoma only after laparoscopic radical nephroureterectomy. Based on this model, an individualized surveillance protocol or adjuvant therapy could be provided.

Effect of HLA genotype on intravesical recurrence after bacillus Calmette-Guérin therapy for non-muscle-invasive bladder cancer.

The intravesical administration of bacillus Calmette-Guérin (BCG) is widely used to control the intravesical recurrence of non-muscle-invasive bladder cancer (NMIBC). This study aimed to reveal the effects of zygosity on human leukocyte antigen (HLA) genes and individual HLA genotypes on intravesical recurrence after intravesical BCG therapy for NMIBC. This study included Japanese patients who had received intravesical BCG for NMIBC. HLA genotyping of HLA-A, B, C, and DRB1 was performed. The effect of HLA zygosity and HLA genotype on intravesical recurrence was evaluated. Among 195 patients, those homozygous for the HLA-B supertype were more likely than those heterozygous for the HLA-B supertype to experience intravesical recurrence by univariate analysis (hazard ratio [HR], 95% confidence interval [CI]; 1.87, 1.14-3.05, P = 0.012) and multivariate analysis (HR, 95% CI; 2.26, 1.02-5.01, P = 0.045). Patients with B07 or B44 had a decreased risk of intravesical recurrence by univariate analysis (HR, 95% CI; 0.43, 0.24-0.78, P = 0.0056) and multivariate analysis (HR, 95% CI; 0.36, 0.16-0.82, P = 0.016). This study suggests the importance of the diversity and specificity of HLA-B loci in the antitumor effect of BCG immunotherapy for NMIBC. These findings may contribute to the delineation of risk strata for BCG therapy and improve the medical management of NMIBC.

Biological distinction between grades 2 and 3 with respect to intravesical recurrence in T1 high-grade bladder tumors: a retrospective study.

BACKGROUND: The pathological grading system for non-muscle-invasive bladder cancer is based on the WHO 2004/2016 classification system (low-grade: LG/high-grade: HG) and the WHO 1973 classification system (Grade 1: G1/Grade 2: G2/Grade 3: G3). Recently, the usefulness of combining both systems and classifying the tumors as LG/G1, LG/G2, HG/G2, and HG/G3 has been demonstrated. In this study, we compared the prognosis of intravesical recurrence in relation to different treatment intensities between HG/G2 and HG/G3 bladder cancers. METHODS: We retrospectively evaluated the clinical and therapeutic outcomes of 145 patients diagnosed with T1 HG bladder cancer between 2000 and 2020. We classified 145 patients into three groups: (1) patients with T1 HG/G2 and HG/G3 who received intravesical instillation therapy (n = 76), (2) patients with T1 HG/G2 who did not receive intravesical instillation therapy (n = 32), and (3) patients with T1 HG/G3 who did not receive intravesical instillation therapy (n = 37). RESULTS: The median intravesical recurrence-free survival for all patients was 34.2 months. The number of tumors, the presence of intravesical instillation therapy, and tumor grade were significant prognostic factors for intravesical recurrence in all cases. Groups 2 and 3 showed significantly worse prognosis than group 1 in the multivariate analysis. CONCLUSIONS: Regarding intravesical recurrence, intravesical instillation therapy is necessary for both T1 HG/G3 and T1 HG/G2 bladder cancers.

Prognostic Analysis of Diagnostic Ureteroscopic Biopsy for Intravesical Recurrence of Upper Urinary Tract Urothelial Carcinoma.

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.

Profiling the Biological Characteristics and Transitions through Upper Tract Tumor Origin, Bladder Recurrence, and Muscle-Invasive Bladder Progression in Upper Tract Urothelial Carcinoma.

To evaluate biological characteristics and transitions of upper tract urothelial carcinoma (UTUC) through metachronous bladder tumors after radical nephroureterectomy (RNU), we conducted immunohistochemical (IHC) staining of tumor specimens of UTUC tumor origin, non-muscle-invasive bladder cancer (NMIBC) and MIBC progressed after intravesical recurrence (IVR), and bladder primary MIBC. Fibroblast growth factor receptor 3 (FGFR3), p53, cytokeratin 5/6 (CK5/6), and CK20 were stained to examine expression rates. After expression assessment with heatmap clustering, the overexpression of four biomarkers from UTUC origin to metachronous MIBC progression was analyzed with clinicopathological variables. We found that high CK20 and low CK5/6 expression were both observed in UTUC tumor origin and subsequent NMIBC after RNU. By investigating molecular expression in the IVR specimen, we observed that low pT stage bladder recurrence occupied the majority of CK20 high CK5/6 low expression, but would change to CK20 low CK5/6 high expression as it progressed to MIBC. UTUC metachronous MIBC has different characteristics compared with bladder primary MIBC, which comprises favorable biological features such as high FGFR3 expression, and follows favorable prognosis compared to those without FGFR3 expression. The present study demonstrated that the biological characteristics of UTUC tumor origin shifts from luminal to basal-like features with progression to MIBC, but FGFR3 expression taken over from UTUC origin may comprise a favorable entity compared to primary MIBC.

The clinicopathological characteristics of muscle-invasive bladder recurrence in upper tract urothelial carcinoma.

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.

Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients.

OBJECTIVE: To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. METHODS: This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. RESULTS: With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P < 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas' model in terms of discriminative capacity (all P < 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients' net benefit. CONCLUSIONS: This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.

Does Xylinas' nomogram accurately predict intravesical recurrence risk after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma when applied to Asian populations?

OBJECTIVE: To validate a prognostic nomogram (Xylinas' nomogram) for intravesical recurrence after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma patients of Asian descent. METHODS: Clinicopathological and survival data from 243 primary urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision between January 2004 and May 2017 were collated. Univariate and multivariable Cox regression analyses were performed to identify independent risk factors associated with intravesical recurrence-free survival. External validation was determined using regression coefficients abstracted from previously published data. Performance was then quantified through calibration and discrimination, according to concordance indexes (c-index) in receiver operating characteristic curves. RESULTS: 163 patients met our eligibility criteria and were finally included in this study. At a median follow-up of 60 months, intravesical recurrence occurred in 29.4% (n = 48). Multivariable analysis revealed that being male, ureteral tumor location, tumor multifocality and previous bladder cancer were independent prognostic factors of intravesical recurrence-free survival. When Xylinas' nomogram was applied to our cohort, the discriminatory power was found to be roughly equivalent with a c-index of 68.3% for the reduced model and 68.4% for the full model. Calibration plots also revealed intravesical recurrence predictions at 3, 6, 12, 18, 24 and 36 months had relative concordance. Contrasting the respective performances of the reduced and full model suggests there is no significant difference between the two (all P > 0.05). CONCLUSIONS: This nomogram appears accurate at predicting intravesical recurrence after radical nephroureterectomy for primary urinary tract urothelial carcinoma in Asian populations. However, it remains necessary to data mine for unknown prognostic factors for optimization. Further external validation is required across larger, ethically diverse populations before applying this nomogram in clinical practice.

Risk factor analysis of intravesical recurrence after retroperitoneoscopic nephroureterectomy for upper tract urothelial carcinoma.

BACKGROUND: One of the major concerns of patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy is intravesical recurrence (IVR). The purpose of the present study was to investigate the predictive risk factors for IVR after retroperitoneoscopic nephroureterectomy (RNU) for UTUC. METHODS: Clinicopathological and surgical information were collected from the medical records of 73 patients treated with RNU for non-metastatic UTUC, without a history of or concomitant bladder cancer. The association between IVR after RNU and clinicopathological and surgery-related factors, including preoperative urine cytology and pneumoretroperitoneum time, was analyzed using the Fisher exact test. RESULTS: During the median follow-up time of 39.1 months, 18 (24.7%) patients had subsequent IVR after RNU. The 1- and 3-year IVR-free survival rates were 85.9% and 76.5%, respectively. The Fisher exact test revealed that prolonged pneumoretroperitoneum time of ≥ 210 min was a risk factor for IVR in 1 year after RNU (p = 0.0358) and positive urine cytology was a risk factor for IVR in 3 years after RNU (p = 0.0352). CONCLUSIONS: In UTUC, the occurrences of IVR in 1 and 3 years after RNU are highly probable when the pneumoretroperitoneum time is prolonged (≥ 210 min) and in patients with positive urine cytology, respectively. Strict follow-up after RNU is more probable recommended for these patients.

The Effect of Diagnostic Ureterorenoscopy on Intravesical Recurrence in Patients Undergoing Nephroureterectomy for Primary Upper Tract Urinary Carcinoma.

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.

Significance of the timing of ureteral ligation on prognosis during radical nephroureterectomy for upper urinary tract urothelial cancer.

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.

Therapeutic options to reduce intravesical recurrence in newly diagnosed Ta high-grade bladder cancer according to risk stratification: A multicenter retrospective study.

OBJECTIVES: To evaluate the risk factors for intravesical recurrence in patients with newly diagnosed Ta high-grade non-muscle-invasive bladder cancer and the optimal management to reduce the risk of recurrence. METHODS: We retrospectively evaluated Ta high-grade bladder cancer in patients who were newly diagnosed by transurethral resection from January 2007 through October 2018. Using multivariate analyses, we evaluated the risk factors and therapeutic options affecting intravesical recurrence and stratified the patients according to the risk numbers. RESULTS: We included 390 patients and the median follow-up period was 31 months after the initial transurethral resection. According to multivariate analysis, having a previous history of upper urinary tract carcinoma, and multiple and sessile tumors were risk factors for intravesical recurrence (P = 0.001, P = 0.02 and P = 0.01, respectively). Risk groups were stratified according to these risk factors into favorable, intermediate and poor. In the entire cohort, induction and immediate intravesical instillation therapy were treatment options to reduce intravesical recurrence (P < 0.01 and P = 0.02, respectively). Analyses in each risk group showed that a second transurethral resection was the only therapeutic option to reduce intravesical recurrence in the favorable group (P = 0.048), whereas induction intravesical instillation therapy was effective in the intermediate and poor risk groups (P = 0.01 and P < 0.01, respectively), as was immediate intravesical instillation for the poor risk group (P < 0.001). CONCLUSIONS: Sessile, multiple tumors and a history of upper urinary tract carcinoma are risk factors for intravesical recurrence in Ta high-grade bladder cancer patients.