Non-metastatic Upper Tract Urothelial Carcinoma Research Articles

Unmarried Status Effect on Stage at Presentation and Treatment Patterns in Non-Metastatic Upper Tract Urothelial Carcinoma Patients

BackgroundUnmarried status has been associated with higher proportions of locally advanced stage and lower treatment dose intensification rates in several urological and non-urological malignancies. However, no previous investigators focused on the association between unmarried status and advanced stage (T3-4N0-2) at presentation and lower nephroureterectomy (RNU) and systemic therapy (ST) rates in non-metastatic upper tract urothelial carcinoma (UTUC) patients. MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, all non-metastatic UTUC patients were identified. Multivariable logistic regression models (LRMs) tested for differences in stage at presentation and treatment (RNU and ST) according to marital status (married vs unmarried), in a sex-specific fashion. ResultsOf all 8544 non-metastatic UTUC patients, 4748 (56%) were male vs 3190 (44%) were female. Of all 4748 male UTUC patients, 1191 (25%) were unmarried. Of all 3190 female UTUC patients, 1608 (50%) were unmarried. In multivariable LRMs predicting RNU, unmarried status was an independent predictor of lower RNU rates in male (Odds Ratio [OR]: 0.56; P < .001), but not in female (OR: 0.81; P = .1) non-metastatic UTUC patients. In multivariable LRMs predicting ST exposure, unmarried status was an independent predictor of lower ST rates in both male (OR:0.73; P = .03) and female (OR:0.64; P < .001) UTUC patients. In multivariable LRMs predicting locally advanced stage (T3-4N0-2), unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male (OR: 0.95; P = .5) or female (OR: 0.99; P = .9) UTUC patients. ConclusionsUnmarried male UTUC patients appear at risk of less being able to access RNU, relative to their married counterparts. Moreover, unmarried UTUC patients appear to less benefit from ST, regardless of sex. Conversely, unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male or female UTUC patients.

Longer is Better for Endoscopic Follow-up of Upper Tract Urothelial Carcinoma After Ureteroscopic Treatment: An Evaluation Spanning 10 Years of Data

BackgroundTumour recurrences are frequent among patients with upper tract urothelial carcinoma (UTUC) treated with ureteroscopy (URS). Therefore, guidelines recommend a strict follow-up regimen, but there is little evidence on how to do this. ObjectiveTo analyse outcomes during our follow-up regimen and the impact on treatment in terms of ipsilateral UTUC recurrence, treatment conversion, and tumour upgrading, and to evaluate potential prognostic factors, including second-look URS outcomes. A secondary objective was to evaluate survival outcomes.Design, setting, and participants: The single-centre cohort included all adult patients with nonmetastatic UTUC treated with URS from January 2010 to December 2020. Follow-up involved endoscopy at 3-mo intervals in the first year, then at 6-mo intervals up to year 3, and yearly thereafter.Outcome measurements and statistical analysis: Descriptive analyses were performed for the follow-up outcomes. The Andersen-Gill model for recurrent event analysis was used to analyse tumour recurrences, and multivariable Cox regression to analyse for predictors for treatment conversion in low-grade tumours. Resultsand limitations: We analysed 71 patients with median follow-up of 49.5 mo. The overall 2-yr recurrence-free survival (RFS) rate was 22%. In low-grade disease, the 1-yr RFS rate was 50% and the 2-yr RFS rate was 29%. Treatment was converted to radical nephroureterectomy for 23 patients, at a median time to conversion of 9.9 mo. Upgrading was seen in 13 patients, at a median time to upgrading of 21.9 mo. No factors were prognostic for either tumour recurrence or treatment conversion. The 5-yr OS, CSS, and MFS rates were 82%, 86%, and 84%, respectively. ConclusionsOur data show that it is rational to extend endoscopic follow-up for UTUC treated with URS, as clinically relevant events (treatment conversion and tumour upgrading) occur beyond the current 6-mo guideline recommendation. Second-look URS outcomes were not prognostic for tumour recurrence or treatment conversion during follow-up. Patient summaryOur study results show that for patients with cancer of the upper urinary tract treated with kidney-sparing surgery through a small telescope called a ureteroscope (URS), most of the clinically relevant events (treatment conversion and tumour upgrading) occur outside the current recommended follow-up of 6 months. Therefore, URS follow-up should be extended for these patients.

Advanced Age Impacts Survival After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma

Upper tract urothelial carcinoma is rare but has a poor prognosis. Prognostic factors have been extensively studied in order to provide the best possible management for patients. We have aimed to investigate commonly available factors predictive of recurrence and survival in this patient population at high risk of death and recurrence, with an emphasis on the effects of age (using a cutoff of 70 years) on survival outcomes. From 1387 patients with clinically nonmetastatic upper tract urothelial carcinoma treated with radical nephroureterectomy at 21 academic hospital centers between 2005 and 2021, 776 patients were eligible and included in the study. Univariable and multivariable Cox regression models were built to evaluate the independent prognosticators for intravesical and extravesical recurrence, overall survival, and cancer-specific survival according to age groups. A P value of <.05 was considered statistically significant. We did not find an association between groups aged <70 and >70 years old and preoperatively clinical or histopathological characteristics. Kaplan-Meier analysis was found no statistical significance between the 2 age groups in terms of intravesical or extravesical recurrence (P = .09 and P = .57). Overall survival (P = .0001) and cancer-specific survival (P = .0001) have been found to be statistically significantly associated with age as independent predictors (confounding factors: gender, tumor size, tumor side, clinical T stage, localization, preoperative hydronephrosis, tumor localization, type of surgery, multifocality of the tumor, pathological grade, lymphovascular invasion, concomitant CIS, lymph node status, necrosis, or history of previous bladder cancer). This research confirms that patients aged 70 and above who undergo radical nephroureterectomy may have worse outcomes compared to younger patients, older patients needing an improved care and management of UTUC to improve their outcomes in the setting of an increase in this aged population group.

Diagnosis and Management of Non-Metastatic Upper Tract Urothelial Carcinoma: AUA/SUO Guideline

The purpose of this guideline is to provide a useful reference on the effective evidence-based diagnoses and management of non-metastatic upper tract urothelial carcinoma (UTUC). The Pacific Northwest Evidence-based Practice Center of Oregon Health & Science University (OHSU) team conducted searches in Ovid MEDLINE (1946 to March 3rd, 2022), Cochrane Central Register of Controlled Trials (through January 2022), and Cochrane Database of Systematic Reviews (through January 2022). The searches were updated August 2022. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (Table 1).[Table: see text]Results:This Guideline provides updated, evidence-based recommendations regarding diagnosis and management of non-metastatic UTUC including risk stratification, surveillance and survivorship. Treatments discussed include kidney sparing management, surgical management, lymph node dissection (LND), neoadjuvant/adjuvant chemotherapy and immunotherapy. This standardized guideline seeks to improve clinicians' ability to evaluate and treat patients with UTUC based on available evidence. Future studies will be essential to further support these statements for improving patient care. Updates will occur as the knowledge regarding disease biology, clinical behavior and new therapeutic options develop.

PD46-09 IS THERE A RACIAL DISPARITY IN THE OUTCOMES OF PATIENTS WITH NON-METASTATIC UPPER TRACT UROTHELIAL CARCINOMA WHO ARE TREATED SURGICALLY? A NORTH AMERICAN NATIONWIDE ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023PD46-09 IS THERE A RACIAL DISPARITY IN THE OUTCOMES OF PATIENTS WITH NON-METASTATIC UPPER TRACT UROTHELIAL CARCINOMA WHO ARE TREATED SURGICALLY? A NORTH AMERICAN NATIONWIDE ANALYSIS Ivan Rakic, Matthew Davis, Nicholas Corsi, Alexander Stephens, Sohrab Arora, Taylor Malchow, Rafe Affas, Akshay Sood, Alexander Cole, Quoc-Dienh Trinh, and Firas Abdollah Ivan RakicIvan Rakic More articles by this author , Matthew DavisMatthew Davis More articles by this author , Nicholas CorsiNicholas Corsi More articles by this author , Alexander StephensAlexander Stephens More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Taylor MalchowTaylor Malchow More articles by this author , Rafe AffasRafe Affas More articles by this author , Akshay SoodAkshay Sood More articles by this author , Alexander ColeAlexander Cole More articles by this author , Quoc-Dienh TrinhQuoc-Dienh Trinh More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003359.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Non-Hispanic Black (NHB) patients with urological cancers, such as prostate or bladder cancer, have been reported to have worse survival outcomes than their Non-Hispanic White (NHW) counterparts. While the reasons for these differences are still controversial, it is plausible that both access to care and genetics play an important role. Our aim is to examine the impact of race on the overall survival (OS) of surgically treated patient with Upper Tract Urothelial Carcinoma (UTUC). METHODS: Our cohort included 9750 cM0 UTUC patients who underwent a radical nephroureterectomy (RNU), between 2004 and 2015, within the National Cancer Database (NCDB). The main variable of interest was race, and it was categorized as NHW, NHB, and others. Kaplan-Meier curves and log-rank test were used to depict and compare survival curves. Cox regression analysis tested the impact of race on OS after accounting for available covariates: age, sex, year of diagnosis Charlson Comorbidity Index, income, treatment center type, insurance status, pathological tumor stage, nodal stage, and pathological LVI status. p-values <0.001 were determined to be significant. RESULTS: Mean (SD) ages at diagnosis for NHW, NHB, and other race were 71.1(10.8), 66.9(12.1), and 71.09(10.9), respectively. Overall, NHW, NHB, and other race was reported in 92.4%, 4.30%, and 3.34%, respectively. The rate of advanced stage (pT3 or higher), pN+disease, and LVI was respectively 39.0%, 5.77%, and 14.5% in NHW, 41.5%, 0.32%, and 13.0% in NHB, and 39.6%, 0.217%, and 16.7% in other race. The mean (SD) follow-up was 42.86±35.3 months. At 5-years, the OS rate was 49.3% in NHW, vs. 46.8% in NHB, and 53.6% in other race (p=0.254). On multivariable analysis, NHB was not an independent predictor of OS outcomes (HR: 1.30, 95% CI: 1.10-1.56, p=0.015), and neither was other (HR 0.90, 95% CI: 0.71-1.15, p=0.015). CONCLUSIONS: Our results indicate that in patients with UTUC treated surgically, NHB patients don’t have a higher stage at diagnosis, and they have similar OS to their NHW counterparts. This is different from other urological cancers, such as prostate cancer where they are very significant differences in terms stage at diagnosis and OS based on race favoring NHW patients. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1173 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ivan Rakic More articles by this author Matthew Davis More articles by this author Nicholas Corsi More articles by this author Alexander Stephens More articles by this author Sohrab Arora More articles by this author Taylor Malchow More articles by this author Rafe Affas More articles by this author Akshay Sood More articles by this author Alexander Cole More articles by this author Quoc-Dienh Trinh More articles by this author Firas Abdollah More articles by this author Expand All Advertisement PDF downloadLoading ...

Preoperative hydronephrosis is an independent protective factor of renal function decline after nephroureterectomy for upper tract urothelial carcinoma.

To evaluate the predictive role of pre-nephroureterectomy (NU) hydronephrosis on post-NU renal function (RF) change and preserved eligibility rate for adjuvant therapy in patients with upper tract urothelial carcinoma (UTUC). This retrospective study collected data of 1018 patients from the Taiwan UTUC Collaboration Group registry of 26 institutions. The patients were divided into two groups based on the absence or presence of pre-NU hydronephrosis. Estimated glomerular filtration rate (eGFR) was calculated pre- and post-NU respectively. The one month post-NU RF change, chronic kidney disease (CKD) progression, and the preserved eligibility rate for adjuvant therapy were compared for each CKD stage. 404 (39.2%) patients without and 614 (60.8%) patients with pre-NU hydronephrosis were enrolled. The median post-NU change in the eGFR was significantly lower in the hydronephrosis group (-3.84 versus -12.88, p<0.001). Pre-NU hydronephrosis was associated with a lower post-NU CKD progression rate (33.1% versus 50.7%, p< 0.001) and was an independent protective factor for RF decline after covariate adjustment (OR=0.46, p<0.001). Patients with pre-NU hydronephrosis had a higher preserved eligibility rate for either adjuvant cisplatin-based chemotherapy (OR=3.09, 95%CI 1.95-4.69) or immune-oncology therapy (OR=2.31, 95%CI 1.23-4.34). Pre-NU hydronephrosis is an independent protective predictor for post-NU RF decline, CKD progression, and eligibility for adjuvant therapy. With cautious selection for those unfavorably prognostic, non-metastatic UTUC patients with preoperative hydronephrosis, adjuvant rather than neoadjuvant therapy could be considered due to higher chance of preserving eligibility.

Comparing Oncological and Perioperative Outcomes of Open versus Laparoscopic versus Robotic Radical Nephroureterectomy for the Treatment of Upper Tract Urothelial Carcinoma: A Multicenter, Multinational, Propensity Score-Matched Analysis

To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990-2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien-Dindo > 3) were assessed between groups. Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan-Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22-2.28, p = 0.001 and HR 1.73, 95%CI 1.22-2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta -1.1, 95% CI -2.2-0.02, p = 0.047 and beta -6.1, 95% CI -7.2-5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31-0.79, p = 0.003 and OR 0.27, 95% CI 0.16-0.46, p < 0.001, respectively). In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.

Inherited mutations in Chinese patients with upper tract urothelial carcinoma

Upper tract urothelial carcinoma (UTUC) accounts for 10% of urothelial carcinomas (UCs) and has a substantial hereditary component. However, the majority of our knowledge of germline spectrum comes from bladder cancer (BCa) data in White populations. Here, we sequence 309 Chinese UTUC cases and identify 71 germline pathogenic/likely pathogenic (P/LP) mutations in 62 patients (20.1%). Compared with White cases, we observe disparities and similarities in inherited mutational profiles. Association analysis reveals that germline P/LP mutations in MSH2, BRCA2, BRCA1, and BRIP1 significantly increase UTUC risk in Chinese populations. Furthermore, germline P/LP mutation in homologous recombination genes indicates poor prognosis for non-metastatic UTUC. Finally, we perform paired sequencing and observe significant correlations between germline mutation patterns and tumor subtypes. This study highlights the importance of genetic testing in patients with UTUC and calls for germline data from various ethnicities to better understand this disease.

Comparing costs of renal preservation versus radical nephroureterectomy management among patients with non-metastatic upper tract urothelial carcinoma.

To describe overall and categorical cost components in the management of patients with non-metastatic upper tract urothelial carcinoma (UTUC) according to treatment. We identified 4,114 patients diagnosed with non-metastatic UTUC from 2004 to 2013 in the Survival Epidemiology and End Results-Medicare linked database. Patients were stratified into renal preservation (RP) vs. radical nephroureterectomy (NU) groups. Total Medicare costs within 1 year of diagnosis were compared for patients managed with RP vs. NU using inverse probability of treatment-weighted propensity score models. A total of 1,085 (26%) and 3,029 (74%) patients underwent RP and NU, respectively. Median costs were significantly lower for RP vs. NU at 90 days (median difference -$4,428, Hodges-Lehmann [H-L] 95% confidence interval [CI], -$7,236 to -$1,619) and 365 days (median difference -$7,430, H-L 95% CI, -$13,166 to -$1,695), respectively. Median costs according to categories of services were significantly less for RP vs. NU patients by hospitalization, office visits, emergency room/critical care, consultations, and anesthesia. The only category which was significantly higher for RP vs. NU was inpatient visits ($1,699 vs. $1,532; median difference $152; HL 95% CI, $19-$286). Median costs were significantly lower for RP vs. NU up to 1-year and by hospitalization, office visits, emergency room/critical care, consultations, and anesthesia costs. In appropriately selected patients, such as patients with low-risk disease, these findings suggest the utility of RP as a suitable high-value management option in UTUC.

Survival Impact of Nephroureterectomy for De Novo Stage IV Nonmetastatic and Metastatic Upper Tract Urothelial Carcinoma.

BackgroundWhether nephroureterectomy (NU) provides survival benefits in patients with stage IV upper tract urothelial carcinoma (UTUC) remains unclear. We compared the effect of chemotherapy (CT) alone with that of CT combined with NU (CT + NU) on the overall survival (OS) of patients with stage IV nonmetastatic UTUC (nmUTUC) and metastatic UTUC (mUTUC).Patients and MethodsThis multicenter retrospective cohort study included the data of patients with UTUC undergoing CT alone or CT + NU from the Chang Gung Cancer Database (2002–2015) and followed them until August 2017. OS and hazard ratios (HRs) were assessed using the Kaplan–Meier method and Cox proportional hazards model, respectively.ResultsThis study included 308 patients with stage IV UTUC, comprising 139 with nmUTUC and 169 with mUTUC. Moreover, 91 (74.6%) patients with nmUTUC and 31 (25.4%) patients with mUTUC received NU. The CT + NU group had a higher 3-year OS rate (41.0.% vs 16.7%, p < 0.001), longer median OS duration (20.7 vs 9.0 months, p < 0.001), and lower risk of death (HR, 0.48; 95% confidence interval, 0.36–0.66; p < 0.001) than did the CT-alone group. Similarly, patients with mUTUC who underwent CT + NU had a longer median OS duration (25.0 vs 7.8 months, p < 0.001) and lower risk of death (HR, 0.37; 95% confidence interval, 0.23–0.59; p < 0.001) than did those who received CT alone.ConclusionCompared with CT alone, NU + CT can provide survival benefits to patients with nonmetastatic and metastatic stage IV UTUC.

MP39-14 COMPARING HEALTHCARE UTILIZATION AND COSTS ACCORDING TO RENAL PRESERVATION VERSUS RADICAL NEPHROURETERECTOMY MANAGEMENT FOR PATIENTS WITH NON-METASTATIC UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyCME1 May 2022MP39-14 COMPARING HEALTHCARE UTILIZATION AND COSTS ACCORDING TO RENAL PRESERVATION VERSUS RADICAL NEPHROURETERECTOMY MANAGEMENT FOR PATIENTS WITH NON-METASTATIC UPPER TRACT UROTHELIAL CARCINOMA Kathryn Fero, Yong Shan, Giri Movva, Jacques Baillargeon, Douglas Tyler, Karim Chamie, and Stephen Williams Kathryn FeroKathryn Fero More articles by this author , Yong ShanYong Shan More articles by this author , Giri MovvaGiri Movva More articles by this author , Jacques BaillargeonJacques Baillargeon More articles by this author , Douglas TylerDouglas Tyler More articles by this author , Karim ChamieKarim Chamie More articles by this author , and Stephen WilliamsStephen Williams More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002599.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Non-metastatic upper tract urothelial carcinoma (UTUC) is a heterogeneous disease with many treatment options that may lead to wide variation in costs. METHODS: We identified 4,114 patients diagnosed with non-metastatic UTUC from 2004-2013 in the Survival Epidemiology and End Results-Medicare linked population-based database. Patients were stratified into low- or high-risk disease groups. Total Medicare costs within one year of diagnosis were compared for patients managed with renal preservation (RP) versus radical nephroureterectomy (NU) using inverse probability of treatment-weighted (IPTW) propensity score models. RESULTS: After risk stratification, 1,027 (25%) and 3,087 (75%) patients were classified into low- vs high-risk UTUC groups and 1,085 (26%) and 3,029 (74%) patients underwent RP and NU, respectively. Median total costs were significantly higher by risk (high vs. low: $141,621 vs. $110,878, p <0.001). Median costs according to categories of services were significantly less for RP vs. NU patients by hospitalization ($22,801 vs. $23,211; Median Difference -$1,369, Hodges-Lehmann (H-L) 95% Confidence Interval (CI), -$2,556 to -$181), office visits ($1,616 vs. $1,874; Median Difference -$238, HL 95% CI, -$340 to -$135), emergency room/critical care ($578 vs. $758; Median Difference -$88, HL 95% CI, -$141 to -$34), consultations ($578 vs. $758; Median Difference -$80, HL 95% CI, -$134 to -$25), and anesthesia ($534 vs. $711; Median Difference -$203; HL 95% CI, -$230 to -$176). The only category which was significantly higher for RP vs. NU was inpatient visits ($1,699 vs. $1,532; Median Difference $152; HL 95% CI, $19 to $286). CONCLUSIONS: Healthcare costs of patients with high-risk UTUC are greater than those of low-risk patients. Median costs were significantly less for RP vs. NU by hospitalization, office visits, emergency room/critical care, consultations, and anesthesia costs. In the absence of data demonstrating superiority of NU over RP, especially for patients with low-risk disease, the increased costs may not be substantiated with equivocal outcomes. Source of Funding: This study was conducted with the support of a Department of Defense Peer Reviewed Cancer Research Program (PRCRP) Career Development Award (W81XWH1710576) (SBW). VS is supported by the Veteran’s Affairs Health Services Research and Development Fellowship. KEF is supported by H&H Lee UCLA Surgical Scholars Program. This project was supported by UroGen Pharma © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e671 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kathryn Fero More articles by this author Yong Shan More articles by this author Giri Movva More articles by this author Jacques Baillargeon More articles by this author Douglas Tyler More articles by this author Karim Chamie More articles by this author Stephen Williams More articles by this author Expand All Advertisement PDF DownloadLoading ...

Neoadjuvant systemic therapy in patients undergoing nephroureterectomy for urothelial cancer: a multidisciplinary systematic review and critical analysis.

The benefit of neoadjuvant systemic therapy (NAST) is not yet supported by randomized controlled trials in upper tract urothelial carcinoma (UTUC), but the evidence is increasing. This narrative systematic review was conducted to evaluate the available evidence on the role of NAST in patients undergoing radical nephroureterectomy (RNU) for UTUC. We searched for all relevant articles or conference abstracts published and indexed in PubMed, Embase, and Scopus on July 19, 2021. The study was reported according to the PRISMA criteria and designed within the PICOS framework. We included studies comparing patients with non-metastatic UTUC who received neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) with patients who underwent definitive surgery alone or surgery plus adjuvant systemic therapy. Prospective uncontrolled studies were also included. We identified 27 reports (NAC, N.=24 and NAI, N.=3) published between 2010 and 2021. Twenty of the 24 studies on NAC were retrospective comparative analyses, whereas the remaining four were prospective single-arm studies. One of the three NAI studies exclusively enrolled patients with UTUC. NAC was associated with improved survival and better pathological response relative to surgery alone, but there was no clear advantage when compared to surgery plus adjuvant chemotherapy. Overall, the drug-induced toxicity and risk of disease progression were acceptable but the inherent bias across study designs, inadequate reporting and heterogeneous definition of primary outcomes render it difficult to synthesize results, compare centers, and inform practice. The current level of evidence supporting NAST for UTUC is relatively low and the inability to predict responsiveness and thereby pinpoint the optimal candidates remains a major challenge. There is a need to compare NAST to adjuvant therapies using clearly defined primary endpoints as minimum reporting standards developed by a multidisciplinary team.

Prognostic value of renal function for upper tract urothelial carcinoma who underwent radical nephroureterectomy: Sex differences

Upper tract urothelial carcinoma (UTUC) is a relatively rare type of urothelial carcinoma. Additionally, only few reports have examined the sex differences in patients with UTUC. Therefore, the present study aimed to identify the sex factors affecting renal function in patients with UTUC who underwent radical nephroureterectomy (RNU). Patients who underwent RNU for non-metastatic UTUC between 2000 and 2013 were retrospectively reviewed and divided into two groups by sex. The Kaplan-Meier method was applied to evaluate the effects of sex on survival, whereas for the other clinicopathological parameters, hazard ratios were evaluated using the Cox regression model. The analyses were also performed in patients with different chronic kidney disease (CKD) stages. A total of 368 patients were included, 147 men and 221 women. Female patients had a higher rate of anemia, advanced CKD stage, and dialysis. Male patients predominantly had a higher rate of smoking. The Kaplan-Meier analysis revealed no differences between sexes on recurrence-free survival (RFS) and cancer-specific survival (CSS). Multivariate analysis confirmed that ureteral tumors, advanced pathological tumor stage, and adjuvant chemotherapy indicated significantly worse survival outcomes in both sexes. However, only female patients with advanced CKD showed poorer RFS. After adjusting for renal function, the analysis found men had worse RFS. The female sex is significantly associated with a higher prevalence of advanced CKD stage, and dialysis among patients with UTUC who underwent RNU in our institute. Sex differences in renal function needs to be considered when evaluating survival.

Lymph Node Dissection During Radical Nephro-Ureterectomy for Upper Tract Urothelial Carcinoma: A Review.

Although lymphonodal dissection is well-accepted for muscle-invasive bladder cancer management, its role is still debated during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). The aim of this study was to summarize the current knowledge concerning the indication, anatomical template, prognostic, and therapeutic roles of lymph node dissection (LND) performed at the time of RNU. Quality control markers, such as the number of lymph nodes (LN) removed, lymph node density, and safety of the different surgical approaches, were assessed. We performed a narrative review using the PubMed and ClinicalTrials.gov databases. We identified and analyzed articles based on the practice and the role of lymph node dissection for non-metastatic UTUC. There are no clear guidelines regarding the indication of LND for UTUC, but aggressive tumors may beneficiate from lymphadenectomy since lymph node invasion is a clear independent poor prognostic factor, allowing for adjuvant treatments. It seems that an extended lymphadenectomy may provide therapeutic advantages as a higher number of nodes removed may be related to the removal of undetected LNs micrometastases and a subsequent improvement in recurrence rate and cancer-specific survival. Clear anatomical templates are thus needed based on the location and the laterality of the primary tumor.

Prognostic Value of Comorbidity for Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy.

Simple SummaryUpper tract urothelial carcinoma (UTUC) is a rare malignancy that occurs mostly in elderly individuals with a high prevalence of comorbidities. However, the prognostic impact of comorbidities in these patients is not well evaluated. The aim of this retrospective study was to assess the significance of Adult Comorbidity Evaluation-27 (ACE-27) grade on the clinical outcomes of 409 patients with non-metastatic UTUC who underwent radical nephroureterectomy. We found that a high ACE-27 grade was an independent risk factor for UTUC progression, UTUC-specific death, and all-cause mortality in multivariate analyses. A prognostic model combining ACE-27 grade, tumor stage, and tumor grade showed good predictive performance and accuracy. Integrating the ACE-27 grade with standard pathological features can help physicians in clinical decision-making and risk stratification.Patients with upper tract urothelial carcinoma (UTUC) have a high prevalence of comorbidities. However, the prognostic impact of comorbidities in these patients is not well studied. We aimed to outline the comorbidity burden in UTUC patients and investigate its relationship with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We retrospectively reviewed the clinicopathological data of 409 non-metastatic UTUC patients who received radical nephroureterectomy between 2000 and 2015. The comorbidity burden was evaluated using the Adult Comorbidity Evaluation-27 (ACE-27). Kaplan-Meier survival analysis showed that high ACE-27 grade was significantly associated with worse PFS, CSS, and OS. In multivariate Cox regression and competing risk analyses, we found that ACE-27 grade, tumor stage, and tumor grade were independent prognosticators of OS, CSS, and PFS. We combined these three significant factors to construct a prognostic model for predicting clinical outcomes. A receiver operating characteristic curve revealed that our prognostic model had high predictive performance. The Harrel’s concordance indices of this model for predicting OS, CSS, and PFS were 0.81, 0.85, and 0.85, respectively. The results suggest that the UTUC patient comorbidity burden (ACE-27) provides information on the risk for meaningful clinical outcomes of OS, CSS, and PFS.

A0306 - Impact of node count on survival outcomes of lymph node dissection in non-metastatic upper tract urothelial carcinoma: Analysis of the robuust registry

A0306 - Impact of node count on survival outcomes of lymph node dissection in non-metastatic upper tract urothelial carcinoma: Analysis of the robuust registry

The hemoglobin, albumin, lymphocyte, and platelet (HALP) score as a prognostic marker for patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy: a retrospective study from two centers

The HALP score, which is the combination of hemoglobin, albumin, lymphocyte, and platelets has been confirmed as an important risk biomarker in several cancers. We aimed at evaluating the prognostic value of the HALP score in patients with non-metastatic upper tract urothelial carcinoma (UTUC). In this study, we retrospectively enrolled 533 of the 640 patients from two centers (315 and 325 patients, respectively) who underwent radical nephroureterectomy (RNU) for UTUC. The cutoff value of HALP was determined using the Youden index by performing receiver operating characteristic curve analysis. The relationship between post-operative survival outcomes and pre-operative HALP level was assessed using Kaplan-Meier and Cox regression analyses. As a result, the cutoff value of HALP was 28.67 and patients were then divided into HALP <28.67 group and HALP ≥28.67 group. Kaplan–Meier analysis and log-rank test revealed that HALP was significantly associated with overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001). Multivariate analysis demonstrated that a lower HALP score was an independent risk factor for OS (HR = 1.54, 95% CI, 1.14-2.01, p = 0.006) and PFS (HR = 1.44, 95% CI, 1.07-1.93, p = 0.020). Nomograms of OS and PFS incorporated with HALP score were more accurate in predicting prognosis than without it. The HALP score could also stratify patients for survival under different pathologic T stages in the subgroup analysis. Therefore, pretreatment HALP score was an independent prognostic factor of OS and PFS in UTUC patients undergoing RNU.

Perineural Invasion is a Powerful Prognostic Factor for Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy.

Taiwan has the highest incidence of upper tract urothelial carcinoma (UTUC) worldwide. Although many pathological factors can predict the prognosis of UTUC, previous studies have rarely discussed perineural invasion (PNI). Therefore, we aimed to investigate the effect of PNI on a well-established cohort of patients with UTUC. This retrospective study included 803 patients with non-metastatic UTUC who underwent radical nephroureterectomy between June 2000 and August 2019. Demographic and clinicopathological parameters, including PNI, were collected for analysis. Using the Kaplan-Meier method and Cox proportional hazards model, we evaluated the significance of PNI with respect to progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). The median follow-up was 30.9 months, and there were 83 cases of PNI (10.3%). PNI-positive patients had unfavorable pathological features, including high pT stage, positive lymph node involvement, high tumor grade, and more lymphovascular invasion (all p<0.001). Kaplan-Meier analysis showed that PNI was significantly associated with PFS, CSS, and OS (all p<0.00001), and when combined with lymphovascular invasion, patients could be divided into groups with distinct survival rates (all p<0.00001). In multivariate analysis, PNI was an independent factor leading to worse PFS (hazard ratio [HR] 1.72, 95% confidence interval [CI] 1.19-2.50; p=0.004), CSS (HR 2.54, 95% CI 1.58-4.10; p=0.0001), and OS (HR 1.78, 95% CI 1.19-2.65; p=0.005). We demonstrated an association between PNI and the prognosis of UTUC. Routine assessment of PNI in UTUC with standardized protocols may help achieve better risk stratification and subject selection for perioperative treatment.

Preoperative models incorporating the systemic immune-inflammation index for predicting prognosis and muscle invasion in patients with non-metastatic upper tract urothelial carcinoma.

To develop preoperative models as a guide to indications for neoadjuvant chemotherapy (NAC) and regional lymph node dissection (LND) before and at radical nephroureterectomy (RNU), respectively, in patients with non-metastatic upper tract urothelial carcinoma (UTUC) by incorporating the systemic immune-inflammation index (SII). This retrospective study enrolled 103 consecutive patients with UTUC undergoing RNU. The SII was calculated as neutrophils × platelets / lymphocytes. Multivariable Cox proportional hazard model was used to develop preoperative models for cancer-specific survival (CSS) and overall survival (OS). A model for predicting muscle invasion was developed using logistic regression analysis. Harrell's concordance-index (c-index) or the area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of the models. During follow-up (median: 41months), 26 and three patients died of UTUC and other causes, respectively. Performance status > 0, clinical tumor (cT) stage ≥ 3, and SII > 520 were independent adverse prognosticators for CSS, and one point was assigned to each prognosticator. Risk score models comprising the sum of the points stratified patients into three risk groups (0, 1, and 2-3; P < 0.001 for CSS and OS) with respective c-indices of 0.843 and 0.820. SII > 677 and ≥ cT3 were independently associated with muscle invasion. A model based on these variables predicted muscle invasion with AUC of 0.804. Preoperative SII is significantly associated with worse survival outcomes and muscle invasion in patients with non-metastatic UTUC. Our preoperative predictive models may serve as a guide to indications for NAC and LND.

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

BackgroundOne 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.MethodsClinicopathological 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.ResultsDuring 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).ConclusionsIn 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.