Radical Nephroureterectomy In Patients Research Articles

A feasibility study of preoperative pembrolizumab before radical nephroureterectomy in patients with high-risk, upper tract urothelial carcinoma: PURE-02.

Advances in neoadjuvant therapy for patients with localized, nonmetastatic, upper tract urothelial carcinoma (UTUC) is needed. PURE-02 was a feasibility study enrolling individuals with UTUC, at clinical stage N0M0, with high-risk features according to the modified European Association of Urology definition, based on the presence of either: high-grade disease, multifocality, tumor size ≥2 cm, and/or hydronephrosis. The treatment consisted of 3 courses of 200 mg pembrolizumab, intravenously, every 3 weeks, followed by radical nephroureterectomy (RNU). The endpoints were to assess the safety, pathological responses, and biomarkers. Ten patients were enrolled between August 2018 and November 2020, 9 (90%) completed the neoadjuvant course. One treatment-related death occurred as a complication of severe myocarditis, myasthenia gravis, hepatitis and myositis. One (14.3%) patient achieved a clinical complete response and refused to undergo RNU. Two (20%) had disease progression and received subsequent chemotherapy, prior to RNU. Overall, 7 patients underwent RNU: one (14.3%) achieved an ypT1N0 response, although this patient was reported to have a cT1 tumor at baseline imaging. The remaining patients were nonresponders. Circulating tumor DNA assay did not identify patients likely to achieve a complete pathologic response. Single-agent neoadjuvant pembrolizumab did not appear to be a promising treatment strategy for patients with biomarker-unselected, high-risk localized UTUC.

The Impact of Upper Tract Urothelial Carcinoma Diagnostic Modality on Intravesical Recurrence after Radical Nephroureterectomy: A Single Institution Series and Updated Meta-Analysis.

Diagnostic ureteroscopic biopsy for upper tract urothelial carcinoma (UTUC) has been hypothesized to increase intravesical recurrence of urothelial carcinoma after radical nephroureterectomy (RNU). Moreover, the impact of ureteroscopy without biopsy or percutaneous biopsy on intravesical recurrence remains unknown. Herein, we compared post-RNU intravesical recurrences across UTUC diagnostic modalities. Patients undergoing RNU at our institution between 1995 and 2019 were categorized by UTUC diagnostic modality: 1) no ureteroscopy or percutaneous biopsy; 2) percutaneous biopsy; 3) ureteroscopy without biopsy; 4) ureteroscopic biopsy. Intravesical recurrences were compared using Kaplan-Meier analyses and Cox-proportional hazard models. Results of group 4 vs 1 were pooled with the literature using a fixed effects meta-analysis. In a cohort of 834 RNU patients, 210 (25.2%) had undergone no ureteroscopy, 57 (6.6%) percutaneous biopsy, 125 (15.0%) ureteroscopy without biopsy, and 442 (53.0%) ureteroscopic biopsy. Two-year intravesical recurrence rates were 15.0%, 12.7%, 18.4%, and 21.9% for groups 1 through 4, respectively (p=0.09). Multivariable analysis found that group 4 had increased intravesical recurrences (HR 1.40, p=0.04) relative to group 1 while group 2 (HR 1.07, p=0.87) and group 3 (HR 1.15, p=0.54) did not. Group 4 remained associated with intravesical recurrence on subset analyses accounting for post-RNU surveillance cystoscopy frequency. On meta-analysis including 11 other series, ureteroscopic biopsy was associated with intravesical recurrence (HR 1.47, p <0.01). Ureteroscopic biopsy before RNU, but not percutaneous biopsy or ureteroscopy without biopsy, was associated with increased intravesical recurrence. Clinical trials of intravesical chemotherapy after ureteroscopic biopsy are warranted to reduce intravesical recurrences.

Preoperative risk stratification using plasma fibrinogen levels can predict lymphovascular invasion and poor prognosis in patients with upper urinary tract urothelial carcinoma.

It has been previously indicated that preoperative plasma fibrinogen levels can correlate with cancer progression and be used as a useful predictor of lymph node metastasis or its premetastatic status such as lymphovascular invasion (LVI). In the present study, how preoperative plasma fibrinogen levels, considered in conjunction with other clinicopathological factors, can predict the presence of LVI and prognosisin patients with upper urinary tract urothelial carcinoma (UTUC) was examined. Medical records of 145 patients with UTUC who underwent radical nephroureterectomy (RNU) were retrospectively reviewed. The current study evaluated systemic inflammatory response markers including levels of plasma fibrinogen and other clinicopathological factors in orderto determine independent predictors of LVI and prognosis. The Cox proportional hazards model indicated that positive surgical margins and LVI were independent factors for poor cancer-specific survival (CSS) rates and extraurothelial recurrence-free survival (ERFS) rates. In addition, positive cytology, the presence of hydronephrosis and plasma fibrinogen levels were significant preoperative predictors of LVI. Furthermore, patients exhibiting two or more of higher fibrinogen levels (≥400 mg/dl), positive urine cytology and the presence of hydronephrosis were indicated to exhibit worse CSS or ERFS rates compared with patients exhibiting only one of the aforementioned factors or those with none of the three aforementioned factors in the multivariate analysis of the Cox proportional hazards model. In conclusion, hyperfibrinogenemia can be an independent predictor of the presence of LVI, and stratifying preoperative risk using fibrinogen levels, urine cytology and hydronephrosis can serve as the basis for selecting candidates for additional therapy before and/or after RNU in patients with UTUC.

Upper Urinary Tract Tumors: Variant Histology Versus Urothelial Carcinoma.

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

Prognostic Impact of pT3 Subclassification in a Multicentre Cohort of Patients with Urothelial Carcinoma of the Renal Pelvicalyceal System Undergoing Radical Nephroureterectomy: A Propensity Score-weighted Analysis After Central Pathology Review

BackgroundThe current pathological tumour-node-metastasis (pTNM) classification for upper tract urothelial carcinoma (UTUC) does not include any risk stratification of pT3 renal pelvicalyceal tumours. ObjectiveTo assess the prognostic impact of pT3 subclassification in a multicentre cohort of patients with UTUC of the renal pelvicalyceal system undergoing radical nephroureterectomy (RNU). Design, setting, and participantsData from all consecutive patients treated with RNU for pT3 renal pelvicalyceal UTUC at 14 French centres from 1995 to 2013 were reviewed retrospectively. InterventionA central pathology review (CPR) was used to stratify pT3 patients into those with infiltration of the renal parenchyma on a microscopic level (pT3a) versus those with infiltration of the renal parenchyma visible on gross inspection of the resection specimen and/or invasion of peripelvic fat (pT3b). Outcome measurements and statistical analysisInverse probability weighting (IPW)-adjusted Cox regression analyses were used to compare recurrence-free survival (RFS) and cancer-specific survival (CSS) between pT3a and pT3b patients. Results and limitationsOverall, 202 patients were included and further stratified into pT3a (n = 98; 48.5%) and pT3b (n = 104; 51.5%) subgroups. Median time to follow-up in the weighted population was 68 (interquartile range, 50–95) mo. In IPW-adjusted Cox regression analyses, pT3b versus pT3a substage was associated with a significant adverse effect on RFS (hazard ratio [HR] = 2.02; 95% confidence interval [CI] = [1.36–3.01]; p < 0.001) and CSS (HR = 1.84; 95% CI = [1.20–2.82]; p = 0.005). The study is limited by its retrospective design. ConclusionsUsing IPW-adjusted analyses after the CPR, we observed that RNU patients with pT3b renal pelvicalyceal UTUC had adverse prognosis as compared with those with pT3a disease. As such, this subclassification could help refine the current pTNM system for UTUC. Patient summaryIn this report, we looked at the prognostic interest of stratifying patients with pT3 renal pelvicalyceal upper tract urothelial carcinoma based on the extent of local invasion. We found that those with extensive infiltration (pT3b) had adverse prognosis as compared with those with limited infiltration (pT3a). This information could be provided on pathology reports to further guide clinical decision making.

760P Platinum-based adjuvant chemotherapy in upper tract urothelial carcinomas (UTUCs): A change of paradigm? A meta-analysis of aggregate data

Upper tract urothelial carcinomas (UTUCs) are a rare subset of urothelial carcinomas arising from urothelial cells of the ureter up to the renal calyceal system. Radical nephroureterectomy (RNU) is the gold standard treatment for UTUC patients, but this surgery leads to high risk of relapse and death from cancer. The present meta-analysis aims to evaluate the role of platinum-based adjuvant chemotherapy (AC) for patients with locally advanced UTUCs (staged as either pT2–T4 N0–N3 M0 or pTany N1–3) after RNU. Eligible studies were identified using Pubmed/Medline, Cochrane library, Embase and meeting abstracts. Searches were last updated on March 30, 2020. Eligible studies reported survival and/or disease-free survival (DFS) outcomes expressed as hazard ratio (HR) and 95% confidence intervals (CIs) for patients treated with platinum-based AC compared to observation alone. Primary outcomes of interest were overall survival (OS), cancer-specific survival (CSS) and DFS. A total of 16 studies were eligible for analysis: 15 retrospective studies and 1 phase 3 randomized control trial (RCT). In total, data from 6275 patients were reported with median number of patients included in each cohort of 65 (range: 11–2491 patients) and a median follow-up of 37,5 months (range 17,8-53,9 months). In patients receiving platinum-based AC, rates of weighted median 5-years OS, CSS and PFS were 72,3%, 75% and 63,3%, respectively, and appeared to be superior compared to control. Platinum-based AC resulted in a 51% risk reduction disease relapse (pooled HR 0.49; 95% CI: 0.36–0.66), while the benefit in OS (pooled HR 0.80; 95% CI: 0.51–1.26) and CSS (pooled HR 0.87; 95% CI: 0.65–1.17) was not statistically significant compared to observation after RNU. Conversely, platinum-based AC showed a modest OS benefit with a pooled HR 0.75 (95% CI: 0.57–0.99) in a posthoc analysis combing multivariable HRs with estimated HRs from Kaplan-Meier curves. With available evidence from published data, we suggest that platinum-based AC is associated with improved DFS and a modest OS benefit after RNU in patients with locally advanced UTUCs. Further prospective randomized studies are needed to confirm our findings.

Comparison of the Comprehensive Complication Index and Clavien-Dindo systems in predicting perioperative outcomes following radical nephroureterectomy.

BackgroundComplications can occur following radical nephroureterectomy (RNU) in 20–40% of patients. The Comprehensive Complication Index (CCI) is an alternative grading system to the Clavien-Dindo (CD) grading system that aggregates all complications experienced by a patient on a continuous (as opposed to categorical) scale. We investigate whether the cumulative nature of CCI renders it superior to CD in predicting perioperative course after RNU.MethodsThe records of 596 patents who underwent RNU at 7 academic medical centers from 2005 to 2015 were reviewed. Complications occurring within 30 days of RNU were annotated using both the CD and CCI classification systems. Logistic regression was used to determine associations between CD and CCI with perioperative covariates as well as measures of convalescence [hospital length of stay (LOS) and readmission].ResultsA total of 377 men and 219 women with a median age of 71, BMI of 27, and Charlson comorbidity score of 4 were included. Over half underwent a minimally invasive RNU. Median LOS following RNU was 6.0 days (range, 1–37 days) and readmission within 30-days occurred in 45 (8%) patients. Overall, 136 patients (23%) experienced a post-operative complication with 91 having a single complication and 45 with multiple (range, 2–6); 44 (7%) patients had Clavien III or greater complications, and the median CCI for those patients experiencing a complication was 20.9 (range, 8.7–100). Both the upper quartile of CCI (≥75th %) and major CD complications were associated with higher baseline Charlson score, ECOG ≥2, and CKD stage ≥ III (all P<0.05). However, only the upper quartile of CCI was associated with LOS (8.9 vs. 5.4 days, P<0.01) and hospital readmission (OR 3.2, 95% CI: 1.9–5.6, P=0.02) after RNU.ConclusionsThe CD and CCI classification systems both are associated with similar baseline and perioperative characteristics for RNU patients. However, the cumulative nature of the CCI allows for superior prediction of postoperative course after RNU including LOS and readmission.

PT358 - Down-grading of ipsilateral hydronephrosis by neoadjuvant chemotherapy is associated with better oncological outcomes after radical nephroureterectomy in patients with ureteral cancer

PT358 - Down-grading of ipsilateral hydronephrosis by neoadjuvant chemotherapy is associated with better oncological outcomes after radical nephroureterectomy in patients with ureteral cancer

Segmental ureterectomy vs. radical nephroureterectomy for ureteral carcinoma in patients with a preoperative glomerular filtration rate less than 90 ml/min/1.73 m2: A multicenter study

ObjectivesTo compare segmental ureterectomy (SU) and radical nephroureterectomy (RNU) in terms of overall survival (OS) and impact on postoperative renal function in patients treated for upper tract urothelial carcinoma (UTUC) of the ureter with preoperatively reduced estimated glomerular filtration rate (eGFR). Materials and methodsWe retrospectively collected the data of consecutive patients treated for UTUC, in 6 Italian tertiary referral centers, from 2003 to 2013, and analyzed those treated with RNU or SU for ureteral cancer and with a preoperative eGFR <90 ml/min/1.73m2. The primary outcome was to compare the postoperative eGFR variation and the OS according to the surgical technique chosen. ResultsOut of 521 patients with UTUC, 228 patients had preoperative reduced eGFR. Out of these patients, 93 had ureteral cancer and were included in the primary analyses – 67 (72.0%) treated with RNU and 26 (28.0%) with SU. Preoperative characteristics were similar in the 2 groups. The overall median follow-up period was 26.5 months. A nonsignificant postoperative eGFR decrease of 3.0 ml/min/1.73m2 was found overall (P = 0.094), with nonsignificant difference between the 2 groups (P = 0.735). A comparable 5-year OS was calculated for RNU and SU patients (P = 0.99). ConclusionsThe type of surgery (SU vs. RNU) has a low impact on postoperative renal function and OS in patients with ureteral cancer and preoperative eGFR <90 ml/min/1.73m2. The indications for kidney sparing surgery for UTUC should be based on the surgical and oncological risks in these patients.

Contemporary conditional cancer-specific survival after radical nephroureterectomy in patients with nonmetastatic urothelial carcinoma of upper urinary tract.

To examine the effect of conditional survival on 5-year cancer-specific survival (CSS) probability after radical nephroureterectomy (RNU) in a contemporary cohort of patients with non-metastatic urothelial carcinoma of the upper urinary tract (UTUC). Within the Surveillance, Epidemiology and End Results database (2004-2015), 6826 patients were identified. Conditional 5-year CSS estimates were assessed after event-free follow-up duration. Multivariable Cox regression (MCR) models predicted cancer-specific mortality (CSM) according to event-free follow-up length. Overall, 956 (14.0%) were T1 low grade(LG)N0 , 1305 (19.1%) T1 high grade(HG)N0 , 1215 (17.8%) T2 N0 , 2249 (32.9%) T3 N0 and 1101 (16.1%) T4 N0 /Tany N1-3 . From baseline, 93.4% to 94.2% in T1 LGN0 provided 5-year CSS and, respectively, 86.2% to 95.3% in T1 HGN0 , 77.5% to 87.8% in T2 N0 , 63.0% to 91.1% in T3 N0 , and 38.8% to 88.2% in T4 N0 /Tany N1-3 . In MCR models, relative to T1 LGN0 , T1 HGN0 (Hazard ratio [HR] 1.7), T2 N0 (HR 3.0), T3 N0 (HR: 5.2), and T4 N0 /Tany N1-3 (HR 11.9) were independent predictors of higher CSM. Conditional HRs decreased to levels equivalent to T1 LGN0 at 3 years vs 5 years of event-free survival for T1 HGN0 and all other groups, respectively. A direct relationship exists between event-free follow-up and survival probability after RNU. From a clinical perspective, such survival estimates may have particular importance during preoperative counseling.

Preoperative frailty predicts adverse short-term postoperative outcomes in patients treated with radical nephroureterectomy.

To investigate the effect of frailty on short-term postoperative outcomes and total hospital charges (THCs) in patients with non-metastatic upper urinary tract carcinoma, treated with radical nephroureterectomy (RNU). Within the National Inpatient Sample (NIS) database we identified 11 258 RNU patients (2000-2015). We used the Johns Hopkins frailty-indicator to stratify patients according to frailty status. Time trends and multivariable logistic, Poisson and linear regression models were applied. Overall, 1801 (16.0%) patients were frail, 4664 (41.4%) were older than 75 years and 1530 (13.6%) had Charlson comorbidity index ≥2. Rates of frail patients increased over time, from 7.3% to 24.9% (P < .001). Frail patients exhibited higher rates (all P < .05) of overall complications (62.6% vs 50.9%), in-hospital mortality (1.6% vs 1.0%), non-home-based discharge (22.7% vs 12.1%), longer length of stay (LOS) (6 vs 1 day) and higher THCs ($49 539 vs $39 644). Moreover, frailty independently predicted (all P < .05) overall complications (OR, 1.46), in-hospital mortality (OR, 1.52), non-home-based discharge (OR, 1.36), longer LOS (RR, 1.30) and higher THCs (RR, +$11 806). Preoperative frailty is important in RNU patients. One of four RNU patients is frail. Moreover, frailty predicts short-term postoperative complications, as well as longer LOS and higher THCs after RNU.

A Novel Risk-based Approach Simulating Oncological Surveillance After Radical Nephroureterectomy in Patients with Upper Tract Urothelial Carcinoma

BackgroundThe current guideline lacks evidence for creating individualized surveillance strategies for upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). ObjectiveTo create a novel risk model and to simulate individualized surveillance duration that dynamically illustrates the changing risk relationship of UTUC-related death and non-UTUC death, considering the impact of cigarette smoking. Design, setting, and participantsThis multicenter cohort study comprised 714 pTa-T4N0M0 UTUC patients, with a median follow-up duration of 65mo. There were 279 (39.1%) nonsmokers, 260 (36.4%) current smokers, and 175 (24.5%) ex-smokers. InterventionAll patients underwent RNU. Outcome measurements and statistical analysisThe risks of UTUC death and non-UTUC death over time were estimated using parametric models for time to failure with Weibull distributions. Age-specific, stage-specific, and smoking status-specific surveillance durations were simulated based upon Weibull estimates. Results and limitationsThe hazard rate (HR) of non-UTUC death gradually increased over time in all age groups regardless of the smoking status, whereas that of UTUC-related death decreased markedly according to the pathological T (pT) stage and was affected by the smoking status. Among current smokers, the baseline HR of UTUC-related death in pT3/4 was higher than that of pT ≤2 and remained high even 10yr after RNU. Among heavy smokers, the HR of UTUC-related death in all pT stages was highest at baseline and remained high after RNU, compared with nonsmokers, current smokers, or ex-smokers. We simulated specific time points when the risk of non-UTUC death was greater than that of UTUC-related death. Among patients ≥80yr of with pT3N0M0, the risk of non-UTUC death was greater than that of UTUC-related death 1yr after RNU in nonsmokers, but 7yr for heavy smokers. ConclusionsOur result revealed that smokers bear a long-term risk burden of UTUC-related death more than the risk of non-UTUC death. For UTUC smokers, longer-term surveillance duration is recommended even in elderly stage. Patient summaryIn the present study, we evaluated the risk transition of upper tract urothelial carcinoma (UTUC)-related death and non-cancer-related death over time. We found that smoking weighed a huge impact upon UTUC-related death compared with death from other cause, and therefore, we created a more individualized surveillance duration model.

Impact of adjuvant chemotherapy on oncologic outcomes following radical nephroureterectomy for patients with pT3NanyM0 upper tract urothelial carcinoma: A retrospective cohort study.

We investigated the impact of cisplatin-based adjuvant chemotherapy (AC) on oncologic outcomes including recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) after radical nephroureterectomy (RNU) for patients with pT3NanyM0 upper tract urothelial carcinoma (UTUC). We retrospectively reviewed 293 patients who underwent RNU for UTUC between 1995 and 2017. Clinicopathologic characteristics of patients were examined and compared according to the use of AC. Kaplan-Meier survival analysis was used to illustrate RFS, CSS and OS. Cox proportional hazard models were applied to identify factors predicting oncologic outcomes. Among the 293 total patients, 127 (43.3%) patients received AC. During a mean follow-up of 59.7 months, recurrence and/or distant metastasis were identified in 124 (42.3%) patients, and 106 (36.2%) patients died overall, of which 93 (31.7%) died from UTUC. The 5-year RFS, CSS and OS rates of overall patients were 51.3%, 68.0% and 64.7%, respectively. In multivariate analysis, AC was inversely associated with tumor recurrence (HR = 0.74, P = 0.028) but not significantly associated with death from UTUC (P = 0.237) and death from all-cause (P = 0.433). The 5-year RFS of patients who had received AC was 58.0%, while 44.0% for patients who had only been observed after RNU. AC improved RFS, but did not have a significant effect on CSS and OS in patients with pT3NanyM0 UTUCs following RNU. Further efforts are needed to identify reliable criteria in the clinic for patients that would benefit from AC.

Transperitoneal radical nephroureterectomy is associated with worse disease progression than retroperitoneal radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma

This study aimed to compare the oncologic outcomes between retroperitoneal radical nephroureterectomy (rRNU) and transperitoneal radical nephroureterectomy (tRNU) for the treatment of patients with upper urinary tract urothelial carcinoma (UTUC). Medical records of 743 eligible patients who underwent rRNU or tRNU between 1995 and 2015 were reviewed retrospectively. Progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) were compared according to the surgical approach using the Kaplan–Meier method. Predictors of PFS, CSS, and OS were analyzed with a multivariable Cox regression model. Overall, 620 (83.4%) and 123 (16.6%) patients were treated with rRNU and tRNU, respectively. Five-year CSS and OS rates were equivalent between rRNU and tRNU groups, but 5-year PFS was lower in the tRNU group than the rRNU group (P = 0.005). When patients were stratified by pathological T stage, PFS was significantly different between the two groups in favor of the rRNU group for both organ-confined disease (pTis/pTa/pT1/T2) (P = 0.022) and locally advanced disease (pT3/pT4) (P = 0.039). However, no significant differences in CSS or OS was observed when comparing the two surgical types in patients with organ-confined disease (P = 0.336 and P = 0.851) or patients with locally advanced disease (P = 0.499 and P = 0.278). tRNU was a significant predictor of PFS (hazard ratio = 1.54; P = 0.023), but not CSS or OS. Our findings indicate that the rRNU approach resulted in better PFS than the tRNU approach in patients with UTUC.

The diagnostic ureteroscopy before radical nephroureterectomy in upper urinary tract urothelial carcinoma is not associated with higher intravesical recurrence

BackgroundTo clarify if diagnostic ureteroscopy (URS) before radical nephroureterectomy for patients with upper tract urothelial carcinoma (UTUC) will increase the risk of intravesical recurrence.MethodsFrom retrospective review of cohort at our institution, 502 patients with UTUC who underwent radical nephroureterectomy with bladder cuff excision were enrolled from 1990 to 2013. Cox proportional hazards model was used to analyze the overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and intravesical recurrence-free survival (IVRFS). The log-rank test was used for comparing survival curves. All potential risk factors were included in the multivariate Cox proportional hazards model to recognize independent predictors. From NHI database, we included patients of UTUC without bladder cancer history using population-based database in Taiwan from 1996 to 2013. In total, 3079 URS and 2634 non-URS patients with UTUC were identified. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of IVRFS and all-cause mortality.ResultsFrom our database, the comparison of clinicopathological characteristics in UTUC patients between with URS biopsy group (URS+) (n = 206, 41%) and without URS biopsy group (URS−) (n = 296, 59%) was insignificantly different excluding surgical method. URS biopsy is not associated with worse OS (p = 0.720), DFS (p = 0.294), MFS (p = 0.808), and IVRFS (p = 0.560) by multivariate analysis. Only bladder cancer history is an independent significant factor to predict IVR (p < 0.001). The same result from NHI database, URS before radical surgery will not increase the risk of IVRFS [adjusted HR 1.136, 95% CI 1.00–1.30; P = 0.059] and OS [adjusted HR 0.919, 95% CI 0.82–1.04; P = 0.164].ConclusionsPreoperative URS manipulation is not associated with higher risk of IVRFS even in patients without bladder cancer history. Diagnostic URS is feasible to compensate the insufficient information of image in patients with UTUC.

Risk-stratified surveillance protocol improves cost-effectiveness after radical nephroureterectomy in patients with upper tract urothelial carcinoma.

ObjectivesTo develop a surveillance protocol with improved cost-effectiveness after radical nephroureterectomy (RNU), as the cost-effectiveness of oncological surveillance after RNU remains unclear.ResultsOf 426 patients, 109 (26%) and 113 (27%) experienced visceral and intravesical recurrences, respectively. The pathology-based protocol found significant differences in recurrence-free survival in the visceral recurrence but not in the intravesical recurrence. The medical costs per visceral recurrence detected were high, especially in normal-risk (≤ pT2N0, LVI-, SM-) patients. We developed a risk score associated with visceral recurrence using Cox regression analysis. The risk score-based protocol was significantly more cost-effective than the pathology-based protocol. Estimated cost differences reached $747,929 per recurrence detected, a suggested 55% reduction.Materials and MethodsWe retrospectively evaluated 426 patients with RNU for upper tract urothelial carcinoma (UTUC) without distant metastasis at 4 hospitals. Patients with routine oncological follow-up were stratified into normal-, high- and very high-risk groups according to a pathology-based protocol utilizing pathological stage, lymphovascular invasion (LVI) and surgical margin (SM). Cost-effectiveness of the pathology-based protocol was evaluated, and a risk score-based protocol was developed to optimize cost-effectiveness. Risk scores were calculated by summing up risk factors independently associated with recurrence-free survival. Patients were stratified by low-, intermediate- and high-risk score. Estimated cost per recurrence detected by pathology-based and risk score-based protocols was compared.ConclusionsA risk score-stratified surveillance protocol has the potential to reduce over investigation during follow-up, making surveillance more cost-effective.

1019 - Risk-stratified surveillance protocol improves cost-effectiveness after radical nephroureterectomy in patients with upper tract urothelial carcinoma

1019 - Risk-stratified surveillance protocol improves cost-effectiveness after radical nephroureterectomy in patients with upper tract urothelial carcinoma

Oncologic outcomes for open and laparoscopic radical nephroureterectomy in patients with upper tract urothelial carcinoma.

Oncologic benefits of laparoscopic radical nephroureterectomy (LNU) are unclear. We aimed to evaluate the impact of surgical approach for radical nephroureterectomy on oncologic outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). Of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017, we retrospectively investigated oncological outcomes in 229 with locally advanced UTUC (stages cT3-4 and/or cN+). The surgical approach was classified as open nephroureterectomy (ONU) or LNU, and oncologic outcomes, including intravesical recurrence-free survival (RFS), visceral RFS, cancer-specific survival (CSS), and overall survival (OS), were compared between the groups. The inverse probability of treatment weighting (IPTW)-adjusted Cox-regression analyses was performed to evaluate the impact of LNU on the prognosis. Of the 229 patients, 48 (21%) underwent LNU. There were significant differences in patient backgrounds, including preoperative renal function, lymph-node involvement, lymphovascular invasion, and surgical margins, between the groups. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS were significantly inferior in the ONU group than in the LNU group. However, in the IPTW-adjusted Cox-regression analysis, no significant differences were observed in intravesical RFS (hazard ratio [HR], 0.65; P=0.476), visceral RFS (HR, 0.46; P=0.109), CSS (HR, 0.48; P=0.233), and OS (HR, 0.40; P=0.147). Surgical approaches were not independently associated with prognosis in patients with locally advanced UTUC.

Significance of multiple preoperative laboratory abnormalities as prognostic indicators in patients with urothelial carcinoma of the upper urinary tract following radical nephroureterectomy.

The aim of this study was to investigate the prognostic significance of multiple preoperative laboratory abnormalities in upper urinary tract urothelial carcinoma (UUTUC) patients. This study included a total of 135 consecutive patients with clinically localized UUTUC who underwent radical nephroureterectomy (RNU). The impact of several preoperative blood-based markers in addition to conventional clinical factors on extravesical recurrence-free survival (eRFS) in these patients was retrospectively evaluated. Despite the lack of a significant correlation between conventional clinical factors and any of the postoperative pathologic parameters, preoperative laboratory abnormalities were shown to have a significant impact on some pathological factors reflecting an aggressive phenotype as follows-C-reactive protein (CRP) level on pathological stage, De Ritis (aspartate transaminase/alanine transaminase) ratio on nodal involvement, and neutrophil-lymphocyte ratio (NLR) on pathological stage. During the observation period of this study (median 36.1months), extravesical disease recurrence was detected in 44 (32.6%) of the 135 patients with a 5-year eRFS rate of 62.1%. Of several factors examined, the CRP level, De Ritis ratio, and NRL were significantly correlated with eRFS on univariate analysis. Of these significant factors, the De Ritis ratio and NRL were identified as independent predictors of eRFS on multivariate analysis. Moreover, there were significant differences in eRFS according to the positive numbers of these two independent risk factors. These findings suggest that it is important to consider laboratory abnormalities, particularly the De Ritis ratio and NLR, to predict disease recurrence following RNU in patients with clinically localized UUTUC.

Preoperative chronic kidney disease predicts poor oncological outcomes after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma.

ObjectiveTo evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes in patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy.MethodsA total of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017 were retrospectively examined. Oncological outcomes, including intravesical recurrence-free, visceral recurrence-free, cancer-specific, and overall survival rates (intravesical RFS, visceral RFS, CSS, and OS, respectively) stratified by preoperative CKD status (CKD vs. non-CKD) were investigated. Cox proportional hazards regression analysis was performed using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and a prognostic factor-based risk stratification nomogram was developed.ResultsOf the 426 patients, 250 (59%) were diagnosed with CKD before radical nephroureterectomy. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS after radical nephroureterectomy were significantly shorter in the CKD group than in the non-CKD group. Background-adjusted IPTW analysis demonstrated that preoperative CKD was significantly associated with poor visceral RFS, CSS, and OS after radical nephroureterectomy. Intravesical RFS was not significantly associated with preoperative CKD. The nomogram for predicting 5-year visceral RFS and CSS probability demonstrated a significant correlation with actual visceral RFS and CSS (c-index = 0.85 and 0.83, respectively).ConclusionsUpper tract urothelial carcinoma patients with preoperative CKD had a significantly lower survival probability than those without CKD.