Radical Nephroureterectomy For Upper Tract Urothelial Carcinoma Research Articles

Comparison of intravesical chemotherapy regimens after radical nephroureterectomy for upper tract urothelial carcinoma and analysis of risk factors for postoperative recurrence.

Upper tract urothelial carcinoma (UTUC) is a relatively rare but aggressive type of urologic cancer that includes renal pelvic tumors and ureteral tumors with a poor prognosis. Full-length nephroureterectomy plus sleeve bladder resection is the standard treatment for the disease, but patients are prone to recurrence of bladder tumors after surgery. Intravesical infusion therapy is the main means to prevent the recurrence and progression of bladder cancer. Epirubicin and gemcitabine are widely used in clinical practice as first-line or salvage therapy for intravesical chemotherapy; however, the efficacy of these agents is rarely discussed. The purpose of this study was to investigate the effects of epirubicin and gemcitabine on the occurrence of bladder cancer after radical nephroureterectomy for UTUC and to analyze the risk factors affecting the recurrence of postoperative bladder cancer. A total of 215 patients with diagnosed UTUC and treated in our hospital from June 2019 to August 2021 were retrospectively selected as the research subjects, and they were divided into an observation group (120 cases) and a control group (95 cases) according to different treatment methods. The patients in the control group were treated with epirubicin, while those in the observation group received gemcitabine. All patients were followed up by telephone or outpatient examination for 12 months to record the occurrence of adverse reactions. The occurrence of bladder cancer was recorded at 3 months, 6 months, and 12 months after the surgery. According to the occurrence of bladder cancer after surgery, the patients were divided into a bladder cancer group (63 cases) and a non-bladder cancer group (152 cases). Multivariate Logistic regression analysis was used to analyze the risk factors of bladder cancer after surgery. The total incidence of adverse reactions in the control group was 49.47%, which was higher than that in the observation group with 15.00% (p<0.01). The incidence of bladder tumors in the observation group and the control group was 0.00% and 2.11% at 3 months, 5.00% and 8.42% at 6 months, 13.33% and 15.79% at 12 months, without significant difference (p>0.05). After 12 months of perfusion, the levels of acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) in the two groups were significantly lower than those before perfusion (p<0.05). In the observation group, the levels of these three factors were slightly decreased compared with those in the control group, without a significant difference (p>0.05). Between the bladder cancer and non-bladder cancer groups, there were significant differences in tumor location, number of lesions, tumor stage, preoperative ureteral examination, and preoperative history of bladder cancer (p<0.05). The above indexes were all risk factors for postoperative bladder cancer (p<0.05). Epirubicin and gemcitabine reduced the occurrence of bladder cancer and effectively inhibited tumor angiogenesis after radical nephroureterectomy for UTUC. The tumor location, number of lesions, tumor stage, preoperative ureteral examination, and preoperative history of bladder cancer were risk factors for postoperative bladder cancer.

Clinical significance of squamous differentiation in upper tract urothelial carcinoma treated with radical nephroureterectomy.

451 Background: Upper tract urothelial carcinoma (UTUC) involving the renal pelvis/ureter is histologically similar to bladder cancer in morphological diversity. Although squamous differentiation (SD) is the most common variant in UTUC, the clinical significance of SD in UC has yet to be comprehensively elucidated given the rarity of the disease compared to bladder cancer. To assess the impact of SD on the prognosis of patients with UTUC undergoing radical nephroureterectomy (RNU). Methods: Among the 244 consecutive patients who underwent RNU at our single institution from May 2005 to October 2019, only patients who had histologically confirmed pure UC or UC with SD (UCSD) were included. SD required the presence of intercellular bridges or keratinization for diagnosis. Metastasis-free survival (MFS) and overall survival (OS) rates were retrospectively evaluated using Kaplan–Meier analysis and Cox regression analysis. Results: We identified 197 (87.9%) and 27 (12.1%) patients with pure UC and UCSD, respectively. No significant differences in age, sex, concomitant carcinoma in situ and tumour grade were observed between the groups. UCSD was significantly associated with an advanced tumour stage and a higher rate of lymphovascular invasion. With a median follow-up time of 58 months, the pure UC and UCSD groups had a 5-year MFS rate of 65.2% and 40.9% ( p=0.005) and a 5-year OS rate of 74.4% and 49.0% ( p=0.002), respectively. Multivariate analyses revealed that the presence of SD was significantly associated with MFS [hazard ratio (HR), 1.88; p=0.027] and OS (HR, 1.70; p=0.048). Conclusions: The patients with UCSD are at high risk for disease metastasis and short-term survival. SD in UC could be an independent predictor of poor prognosis after RNU for UTUC.

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.

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). 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: 110months) and 39 patients received a 6-month (4 times weekly, 5 times monthly) maintenance regimen of MMC (median follow up: 48months). The primary outcome was the 1-, 2- and 5-year bladder recurrence free survival (BRFS). 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. 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.

Changes in renal function after nephroureterectomy for upper urinary tract carcinoma: analysis of a large multicenter cohort (Radical Nephroureterectomy Outcomes (RaNeO) Research Consortium)

PurposeTo investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).MethodsPatients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)—1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR − baseline eGFR; Δ2 = 6 months eGFR − POD-1 eGFR; Δ3 = 12 months eGFR − 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up.ResultsA total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR < 60 ml/min at 6 and 12 months, respectively, and 239(41.5%) developed POD-1 AKI. In multivariable LR analysis, age (Odds Ratio, OR 1.05, p < 0.001), male gender (OR 0.44, p = 0.003), POD-1 AKI (OR 2.88, p < 0.001) and preoperative eGFR < 60 ml/min (OR 7.58, p < 0.001) were predictors of renal function decline at 6 months. Age (OR 1.06, p < 0.001), coronary artery disease (OR 2.68, p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR < 60 ml/min (OR 7.80, p < 0.001) were predictors of renal function decline at 12 months. In LM models, age (p = 0.019), hydronephrosis (p < 0.001), POD-1 AKI (p < 0.001) and pT-stage (p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p < 0.001) during follow-up.ConclusionAge, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC.

Factors Predicting Oncological Outcomes of Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma in Taiwan.

BackgroundTaiwan 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.ObjectiveThis 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.MethodsA 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.ResultsWith 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.ConclusionSynchronous 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.

Prognostic Value of Squamous Differentiation in Upper Tract Urothelial Carcinoma Treated With Radical Nephroureterectomy.

This study retrospectively investigated the impact of squamous differentiation on the prognosis of patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Among the 244 consecutive patients who underwent RNU at our Institution from May 2005 to October 2019, 224 were analysed. Metastasis-free (MFS) and overall (OS) survival rates were evaluated using Kaplan-Meier analysis and Cox regression analysis. With a median follow-up time of 58 months, the groups with pure UTUC (n=197) and UTUC with squamous differentiation (n=27) had 5-year MFS rates of 65.2% and 40.9% (p=0.005) and 5-year OS rates of 74.4% and 49.0% (p=0.002), respectively. Multivariate analyses revealed that the presence of squamous differentiation was significantly associated with poor MFS (hazard ratio=1.88; p=0.027) and OS (hazard ratio=1.70; p=0.048). Squamous differentiation in UTUC appears to be an independent predictor of poor prognosis after RNU for UTUC.

MP48-10 THE ROLE OF PRIOR BLADDER CANCER ON ANY RECURRENCE AND DISTANT METASTASIS IN PATIENTS TREATED WITH RADICAL NEPHROURETERECTOMY

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma II (MP48)1 Sep 2021MP48-10 THE ROLE OF PRIOR BLADDER CANCER ON ANY RECURRENCE AND DISTANT METASTASIS IN PATIENTS TREATED WITH RADICAL NEPHROURETERECTOMY Alberto Martini, Chiara Lonati, Andrea Necchi, Alberto Briganti, Francesco Montorsi, Agostino Mattei, Luca Afferi, Stefania Zamboni, Claudio Simeone, Shahrokh F. Shariat, and Marco Moschini Alberto MartiniAlberto Martini More articles by this author , Chiara LonatiChiara Lonati More articles by this author , Andrea NecchiAndrea Necchi More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Agostino MatteiAgostino Mattei More articles by this author , Luca AfferiLuca Afferi More articles by this author , Stefania ZamboniStefania Zamboni More articles by this author , Claudio SimeoneClaudio Simeone More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , and Marco MoschiniMarco Moschini More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002074.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Literature lacks clear evidence regarding the association between history of prior UC and survival outcomes in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). We aimed to investigate the role of prior UC on any recurrence (aR) and distant metastasis (DM) following RNU for low grade (LG) and high grade (HG) UTUC. METHODS: We retrospectively analyzed data of 1583 patients treated with RNU for UTUC at 8 tertiary referral centers between 1992 and 2016. aR was defined as recurrence in the urinary tract, in the resection bed as well the presence of DM, defined as metastatic disease outside the urinary tract and regional lymph nodes. Time to aR and DM were computed from RNU. First, we investigated the role of prior UC on aR and DM. Multivariable Cox models were generated to predict risk of aR and DM according to prior history of UC, distinguished into no prior UC, non-muscle invasive (NMIBC) and muscle invasive bladder cancer (MIBC). Second, we evaluated the effect of prior UC on overall survival (OS) among patients experiencing aR. RESULTS: Median follow-up for survivors was 3.6 years. Overall, 71%, 25% and 4% of patients had no history of prior UC, NMIBC and MIBC, respectively. 5-year aR-free rates were 61%, 41% and 19% in LG UTUC patients (p<0.001) and 42%, 34% and 30% in HG UTUC (p=0.1), respectively in patients with no prior UC, NMIBC and MIBC (Fig. 1A and 1B). 5-year DM-free rates were 92%, 90% and 87% in LG UTUC patients (p>0.05) and 68%, 75% and 45% in HG UTUC patients (p=0.01) according to no prior UC, NMIBC and MIBC, respectively (Fig. 1C and 1D). At multivariable analyses, prior NMIBC was associated to a higher risk of aR among LG (p<0.005) and HG UTUC patients (p=0.04) compared to no prior UC, while prior MIBC correlated to a higher risk of aR in LG UTUC patients. Among patients experiencing aR, 5-years OS after recurrence was 73% vs. 90% (p=0.003) in LG UTUC and 27% vs. 38% (p=0.05) in HG UTUC patients without and with prior UC, respectively. CONCLUSIONS: Patients with a prior history of UC are at a higher risk of experiencing aR after RNU for both LG and HG UTUC. Our study provides important information which could address patient’s counseling and decision-making process. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e867-e867 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alberto Martini More articles by this author Chiara Lonati More articles by this author Andrea Necchi More articles by this author Alberto Briganti More articles by this author Francesco Montorsi More articles by this author Agostino Mattei More articles by this author Luca Afferi More articles by this author Stefania Zamboni More articles by this author Claudio Simeone More articles by this author Shahrokh F. Shariat More articles by this author Marco Moschini More articles by this author Expand All Advertisement Loading ...

Prognostic value of Balkan endemic nephropathy and gender on upper tract urothelial carcinoma outcomes after radical nephroureterectomy: A cohort study

BackgroundTo identify the prognostic impact of residence in a BEN-endemic area and gender on upper tract urothelial carcinoma (UTUC) outcomes in Serbian patients treated with radical nephroureterectomy (RNU). MethodsThe study included 334 consecutive patients with UTUC. Patients with permanent residence in Balkan endemic nephropathy (BEN) or non-endemic areas from their birth to the end of follow-up were included in the analysis. Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. ResultsFemale patients were more likely to have preoperative pyuria (P = 0.01), tumor multifocality was significantly associated with the female gender (P = 0.003). Gender was not associated with pathologic stage and grade, lymph node metastasis, lymphovascular invasion, adjuvant chemotherapy, bladder cancer history, tumor size, distribution of tumor location, preoperative anemia and demographic characteristics. A total of 107 cases recurred, with a median time to bladder recurrence of 24.5 months. History of bladder tumor (HR, 1.98; P = 0.005), tumor multifocality (HR, 3.80; P < 0.001) and residence in a BEN-endemic area (HR, 1.81; P = 0.01) were independently associated with bladder cancer recurrence. The 5-year bladder cancer RFS for the patients from areas of BEN was 77.8 % and for the patients from non-BEN areas was 64.7 %. The 5-year CSS for the men was 66.2% when compared to 66.6% for the women (P = 0.55). ConclusionsResidence in a BEN-endemic area represents an independent predictor of bladder cancer recurrence in patients who underwent RNU. Gender cannot be used to predict outcomes in a single-centre series of consecutive patients who were treated with RNU for UTUC.

Prognostic significance of tumor multifocality on outcomes in patients with upper tract urothelial carcinoma after radical nephroureterectomy: A cohort study

To identify the prognostic impact of tumor multifocality on upper tract urothelial carcinoma (UTUC) outcomes in patients treated with radical nephroureterectomy (RNU). Study included 342 consecutive patients with UTUC. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location. Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. Tumor multifocality was significantly associated with a history of previous non-muscle invasive bladder cancer (P < 0.001), tumor size (P < 0.001), gender (P = 0.009), tumor location (P = 0.005), and anemia (P = 0.01). The Kaplan–Meier method showed that tumor multifocality was significantly associated with worse recurrence-free survival (P < 0.001, log rank). Using multivariate analysis, tumor multifocality (HR, 2.86; 95% CI, 2.06 – 3.99; P < 0.001) was independently associated with recurrence free survival. During the follow-up, a total of 128 (37.4%) patients died, including 92 (28.2%) from UTUC. However, tumor multifocality was not associated with CSS (HR, 1.29; 95% CI, 0.89 – 1.96; P = 0.21) in univariate Cox regression analyses. Tumor stage (HR, 11.1; 95% CI, 3.64 – 33.8; P < 0.001), lymph node status (HR, 2.04, 95% CI, 1.05 – 3.94; P = 0.03) and preoperative anemia (HR, 3.50, 95% CI, 2.02 – 6.08; P < 0.001) were the only independent predictors associated with worse cancer-specific survival. Tumor multifocality is an independent prognostic factor of disease recurrence in patients treated with RNU for UTUC. Tumor multifocality is unable to predict cancer specific survival in a single-center series of consecutive patients who were treated with RNU.

Prognostic role of the systemic immune\u2013inflammation index in upper tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration

PurposeTo investigate the prognostic role of the preoperative systemic immune–inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU).Materials and methodsWe retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS).ResultsOverall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis.ConclusionsPreoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.

Preoperative predictors of pathological tumour stage and prognosis may be used when selecting candidates for intensified treatment in upper tract urothelial carcinoma

Purpose Intensified treatment such as extended lymph node dissection (LND) and/or perioperative chemotherapy in addition to radical nephroureterectomy (RNU) has been suggested for high-risk cases of upper tract urothelial carcinoma (UTUC). We aimed to identify preoperative predictors of tumour stage and prognosis in the diagnostic work-up before RNU. Further to evaluate if our findings could be used in selecting patients for intensified treatment. Patients and methods A total of 179 patients treated with RNU for UTUC at Haukeland University Hospital (HUS) and Vestfold Hospital Trust (VHT) during 2005–2017 were included in this retrospective study. All relevant preoperative variables regarding the patient, the CT and the ureteroscopy (URS) were registered and analysed regarding their ability to predict non-organ confined disease (NOCD, pT3+ and/or N+) at final pathology after RNU. The prognosis was assessed calculating survival for the cohort and stratified by preoperative variables. Results Local invasion and pathological lymph nodes at CT predicted NOCD in uni and multivariate regression analyses (OR 3.36, p=.004 and OR 6.21, p=.03, respectively). Reactive oedema surrounding the tumour (OR 2.55, p=.02), tumour size (4.8 vs. 3.9 cm, p=.006) and high-grade tumour at URS biopsy (OR 3.59, p=.04) predicted NOCD at univariate regression analyses. The 5-year CSS and OS for the entire cohort was 79% and 60%. ECOG, local invasion, pathological lymph nodes and reactive oedema surrounding the tumour at CT predicted CSS. Conclusions Several variables at the CT predicted both stage and survival. Local invasion at CT seems the most promising feature for selecting patients for intensified treatment.

Postoperative Chemotherapy Bladder Instillation After Radical Nephroureterectomy: Results of a European Survey from the Young Academic Urologist Urothelial Cancer Group

BackgroundLevel 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk. ObjectiveThe Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues. Design, setting, and participantsAn online survey was shared with European Association of Urology Section of Oncological Urology (ESOU) 2017 participants via e-mail. Submissions were accepted from April to June 2017. The topics for 15 questions of this survey included the habit of delivering pIVC, the choice of drug, its dosage, related doubts or concerns, reasons not to perform pIVC, knowledge of the evidence, and surgical preferences for RNU. Outcome measurements and statistical analysisSurvey software was used for analyses. Logistic regression analyses were used to investigate the association between surgeons’ experience and caseloads with pIVC utilization. Results and limitationsOverall, 127 responses were collected (11.6%). About half of the participants (47%) regularly administered pIVC following RNU. The drug most commonly utilized was mitomycin (85%); 82% adhered to the standard dosage of 40 mg. Different administration protocols were adopted: ≤48 h (39%), 7–10 postoperative days (35%), >10 d (11%), and intraoperatively (10%). The evidence was supported by prospective randomized clinical trials for only 65% of responders. Among interviewees who did not deliver pIVC, the most commonly reported reasons were lack of supporting data (55%), fear of potential side effects (18%), and organizational hurdles (15%). ConclusionsOur research highlights the limited use of pIVC following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted. Patient summaryLevel 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk. The Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues. Our research highlights the limited use of pIVC (47%) following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted.

GEMINI: An open-label, single-arm, phase II trial of intraoperative gemcitabine intravesical instillation in patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma.

TPS594 Background: The standard treatment for upper tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU) with bladder cuff resection. Subsequent intravesical recurrence is common and results in patient morbidity and increased healthcare cost. Level 1 evidence has demonstrated reduction of intravesical recurrence with instillation of intravesical Mitomycin C at 10 days following RNU. However, there has been limited adoption of Mitomycin C due to concerns for toxicity and logistics of postoperative drug delivery. Meanwhile, immediate intravesical gemcitabine has been shown to reduce intravesical recurrence following transurethral resection of bladder cancers without increasing toxicity compared to placebo. Moreover, small series have suggested improved efficacy of intraoperative intravesical chemotherapy for RNU. The purpose of the GEMINI trial, therefore, is to prospectively establish the safety and efficacy of intraoperative instillation of intravesical gemcitabine in patients undergoing RNU for UTUC. Methods: GEMINI is a multi-center open-label, single-arm, Phase II study that aims to enroll 90 patients with cTa-T4N0M0 UTUC. Patients receive intraoperative intravesical instillation of gemcitabine at the beginning of RNU, to be held in the bladder for at least 1 hour. The instilled drug will be drained prior to resection of the bladder cuff. Patients will undergo standard of care postoperative surveillance, including cystoscopy at 3, 6, 12, 18, and 24 months. The primary endpoint is 1-year intravesical recurrence-free survival. The historical event rate for no treatment is 30%, and we estimated a 40% relative reduction in event rate with gemcitabine. The study is powered to provide 80% power to detect this difference based on a one-sided exact test of proportions with alpha level 0.05. Secondary endpoints include time to recurrence and stratification of recurrence free survival by tumor grade, tumor stage, neoadjuvant chemotherapy, ureteral tumor location, and history of bladder cancer. Safety and adverse event endpoints will be evaluated. Complete accrual is expected within 3 years.

Current Status of Lymphadenectomy During Radical Nephroureterectomy for Upper Tract Urothelial Cancer-Yes, No or Maybe?

While pelvic lymphadenectomy during radical cystectomy for bladder cancer is a well-established standard of care, the same does not hold true for upper tract urothelial carcinoma (UTUC). Indeed, a template-based lymphadenectomy is rarely, if ever, performed in conjunction with radical nephroureterectomy at most centres across the globe. While multiple studies have explored the staging and therapeutic role of lymphadenectomy in cases of UTUC, there remain large gaps in our understanding of the indications, extent and safety of this procedure as an adjunct to nephroureterectomy. This article elucidates the current knowledge on outcomes, benefits and complications of template-based lymphadenectomy during radical nephroureterectomy for UTUC. We also explore the current evidence-based guidelines on this controversial topic.

Prognostic Impact of Preoperative Albumin-Globulin Ratio on Oncologic Outcomes in Upper Tract Urothelial Carcinoma Treated With Radical Nephroureterectomy.

To identify the impact of albumin-globulin ratio (AGR) on pathologic and survival outcomes in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We retrospectively reviewed medical records of 620 patients treated with RNU for UTUC at our institution. Logistic regression analysis was used to evaluate the relation between low AGR (<1.45) and adverse pathologic features. Kaplan-Meier curves were used to estimate recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) probabilities between 2 groups. Univariable and multivariable Cox regression models were performed to address prognostic factors related to RFS, CSS, and OS. Of the 620 patients, 323 (52.1%) had AGR< 1.45. During a median follow-up of 50.0 months (interquartile range, 28-78 months), 277 (44.7%) experienced disease recurrence and 194 (31.3%) died of disease. The results showed that low AGR was significantly associated with adverse pathologic features (all P< .05). Kaplan-Meier analysis showed that compared to those with high AGR (≥1.45), patients with low AGR had poorer RFS, CSS, and OS (P< .001). After adjusting for the confounding clinicopathologic factors, multivariate analyses showed that AGR< 1.45 independently predicted poor RFS (hazard ratio [HR]= 1.321, P= .029), CSS (HR= 1.503, P= .010) and OS (HR= 1.403, P= .015). Low preoperative AGR is an independent predictor of worse pathologic and oncologic outcomes in patients with UTUC after RNU. The application of AGR as an easily assessed blood-based biomarker in predicting the prognosis of patients with UTUC is promising.

MP18-16 COMORBIDITY STATUS INDEPENDENTLY PREDICTS OVERAL SURVIVAL AFTER RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma I1 Apr 2018MP18-16 COMORBIDITY STATUS INDEPENDENTLY PREDICTS OVERAL SURVIVAL AFTER RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA Ryan McLarty, Niels Jacobsen, Derek Tilley, Jan Rudsinski, Ben Beech, Nick Dean, Steven Tong, Adrian Fairey, and Dylan Hoare Ryan McLartyRyan McLarty More articles by this author , Niels JacobsenNiels Jacobsen More articles by this author , Derek TilleyDerek Tilley More articles by this author , Jan RudsinskiJan Rudsinski More articles by this author , Ben BeechBen Beech More articles by this author , Nick DeanNick Dean More articles by this author , Steven TongSteven Tong More articles by this author , Adrian FaireyAdrian Fairey More articles by this author , and Dylan HoareDylan Hoare More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.592AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Radical nephroureterectomy (RNU) with or without regional lymph node dissection is a standard of care treatment for upper tract urothelial carcinoma (UTUC). Independent predictors of survival after RNU are pathologic TNM stage, LVI and WHO grade. Comorbidity status has previously been shown to not be an independent predictor of survival. The objective of the current study was to re-examine the association between comorbidity status and survival after RNU for UTUC. METHODS A retrospective analysis of data from the University of Alberta (UA) Radical Nephroureterectomy Database was performed. Between April 1994 and August 2017, 255 consecutive patients underwent RNU with or without regional lymph node dissection for UTUC at 2 academic teaching hospitals. Comorbidity status was obtained through a medical record review and classified using the Charleson Comorbidity Scale (CCS). The main outcome was overall survival (OS). The Kaplan-Meier method and Cox proportional regression models were used to analyze survival data. Statistical tests were two-sided (p≤0.05). RESULTS Data were evaluable for 255 patients. The median follow-up duration was 52.4 months. The median age was 71 years (IQR, 34 to 89 years) and 157 patients (61%) were male. 35 (13%) and 220 (87%) patients had CCS<2 and CCS≥2 comorbidity, respectively. The 5-year OS rates for patients with CCS<2 and CCS≥2 comorbidity were 97% and 67%, respectively (Log rank p<0.001). Multivariate Cox regression analyses showed that increased comorbidity was independently associated with worse OS (HR 5.7, 95% CI 2.3 to 14.1, p<0.001). CONCLUSIONS This is the first study to show comorbidity status, as measured by the CCS, was independently associated with overall survival after RNU for UTUC. Further prospective validation is required. This data has implications for patient counseling and use of CCS as stratification variable in clinical trials. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e219-e220 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Ryan McLarty More articles by this author Niels Jacobsen More articles by this author Derek Tilley More articles by this author Jan Rudsinski More articles by this author Ben Beech More articles by this author Nick Dean More articles by this author Steven Tong More articles by this author Adrian Fairey More articles by this author Dylan Hoare More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effects of tumor size and location on survival in upper tract urothelial carcinoma after nephroureterectomy.

Introduction:Upper Tract Urothelial Carcinoma (UTUC) is a rare disease with few prognostic determinants. We sought to evaluate the impact of tumor size and location on patient survival following nephroureterectomy for UTUC.Materials and Methods:Data on 8284 patients treated with radical nephroureterectomy for UTUC in the United States between 1998 and 2011 were analyzed from the National Cancer Data Base. Univariable survivorship curves were generated based on pT stage, pN stage, grade, tumor size, and tumor site (renal pelvis vs. ureter). A Cox proportional hazards model was used to evaluate the effect of age, comorbidity, T stage, lymph node involvement, tumor site, and tumor size on survival.Results:The median follow-up time was 46 months. A majority of the patients were male (55.4%) with a tumor size of ≥3.5 cm (52.0%) and pT stage <T2 (47.8%). The overall 5 years survival overall survival (OS) for the entire cohort was 51.6%. When stratified by tumor size <3.5 cm or ≥3.5 cm the 5-year OS was 45.9% and 58.5%, respectively. On multivariable analysis controlling for age, Charlson comorbidity index, grade, and tumor stage, tumor size ≥3.5 cm was independently predictive of worse OS (odds ratio: 1.13 [95% confidence interval: 1.02–1.26], P = 0.023).Conclusions:Using the largest series of patients with UTUC undergoing nephroureterectomy, we demonstrated a worse survival in patients with larger tumor sizes (≥3.5 cm) but no difference in survival based on tumor location while controlling for other pathologic characteristics. Incorporation of tumor size into perioperative risk modeling may help with patient stratification and provide further prognostic information for patient counseling.

Impact of body mass index on the oncological outcomes of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma.

To evaluate the association between body mass index (BMI) and oncological outcomes in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). We retrospectively reviewed 237 consecutive patients treated with RNU for UTUC at our institution between 1990 and 2012. Univariable and multivariable cox regression models investigated the association of BMI with disease recurrence, cancer-specific mortality, and overall mortality. From the 237 patients, 104 (44%) had a BMI<25kg/m2, 88 (37%) had a BMI between 25 and 29.9kg/m2, and 45 (19%) had a BMI≥30kg/m2 at the time of surgery. Within a median follow-up of 44months (IQR: 24-79), 53 patients (22.4%) experienced a disease recurrence, 85 patients (35.9%) had bladder recurrence, and 44 patients (18.6%) died from the disease. The 5year recurrence-free and cancer-specific survival rates were, respectively, 32 and 56% for BMI≥30kg/m2, 45 and 74% for patients with BMI 25-29.9kg/m2, and 69 and 81% for patients with BMI<25kg/m2. In multivariable analyses that adjusted for the effects of the standard clinico-pathological features, BMI≥30kg/m2 was associated with a higher risk of disease recurrence (HR 3.23; 95% CI 2.3-6.6, p<0.001) and cancer-specific mortality (HR 3.84; 95% CI 2.8-6.5; p<0.001). Obesity was independently associated with higher risks of disease recurrence and cancer-specific mortality in patients treated with RNU for UTUC.

HER2 and TOP2A Gene Amplification and Protein Expression in Upper Tract Urothelial Carcinomas.

HER2, a potential target for therapy, has been described to be amplified in urothelial carcinomas. As the topoisomerase II alpha (TOP2A) gene is located close to the HER2 gene on chromosome 17q12-q21, it is frequently either co-amplified or deleted with HER2 amplification. The purpose of this study was to assess the impact HER2 and TOP2A gene amplification as well as protein expression on outcomes of upper tract urothelial carcinoma (UTUC). HER2 and TOP2A gene amplification and protein expression were assessed in 81 patients with radical nephroureterectomy for UTUC. Immunohistochemistry and chromogenic in-situ hybridization was performed on formalin-fixed, paraffin-embedded samples. HER2 protein expression was observed in 27/81 (33%) cases, of which 8 cases exhibited amplification of HER2. One of them had an additional polysomy 17, whereas 6/67 HER2 non-amplified cases revealed a polysomy 17. Coamplification of HER2 and TOP2A was found in 4 cases, whereas 3 cases showed only HER2 amplification and 20 cases only TOP2A amplification. HER2 IHC overexpression was associated with higher-grade tumors (p=0.001), non-organ confined carcinomas (p=0.017), HER2 amplification (p<0.00001) and TOP2A amplification (p=0.016). HER2 amplification was association with higher tumor grade (p=0.001) and lymphnode metastasis (p=0.003). TOP2A IHC positivity was significantly associated with higher tumor grade (p=0.0004), TOP2A amplification (p=0.0003), polysomy 17 (p=0.035) and HER2 IHC overexpression (p=0.28), whereas all categories of tumor stage and HER2 amplification remained not related. TOP2A amplification was significantly more frequent in tumors with higher grade, higher tumor stage, polysomy 17 and distant metastasis (p=0.015; p=0.042; p=0.032; p = 0.011), respectively. In univariate analyses HER2 IHC positivity, TOP2A amplification, and polysomy 17 were associated with poor clinical outcome after surgery. HER2 IHC overexpression and TOP2A amplification are associated with features of biologically aggressive UTUC. Overexpression and/or amplification of HER2 and TOP2A could help identify patients who may benefit from targeted therapy.

Diagnostic Ureteroscopy for Upper Tract Urothelial Carcinoma is Independently Associated with Intravesical Recurrence after Radical Nephroureterectomy.

ABSTRACTPurpose:To determine the effect of diagnostic ureteroscopy on intravesical recurrence in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).Materials and Methods:We conducted a retrospective analysis of 664 patients who were treated with RNU for UTUC from June 2000 to December 2011, excluding those who had concomitant/prior bladder tumors. Of the 664 patients, 81 underwent diagnostic ureteroscopy (URS). We analyzed the impact of diagnostic ureteroscopy on intravesical recurrence (IVR) using the Kaplan-Meier method. Univariate and multivariate analyses were used to determine the independent risk factors.Results:The median follow-up time was 48 months (interquartile range (IQR): 31-77 months). Patients who underwent ureteroscopy were more likely to have a small (p<0.01), early-staged (p=0.019), multifocality (p=0.035) and ureteral tumor (p<0.001). IVR occurred in 223 patients during follow-up within a median of 17 months (IQR: 7-33). Patients without preoperative ureteroscopy have a statistically significant better 2-year (79.3%±0.02 versus 71.4%±0.02, p<0.001) and 5-year intravesical recurrence-free survival rates (64.9%±0.05 versus 44.3%±0.06, p<0.001) than patients who underwent ureteroscopy. In multivariate analysis, the diagnostic ureteroscopy (p=0.006), multiple tumors (p=0.001), tumor size <3cm (p=0.008), low-grade (p=0.022) and pN0 stage tumor (p=0.045) were independent predictors of IVR.Conclusions:Diagnostic ureteroscopy is independently associated with intravesical recurrence after radical nephroureterectomy.