Ureteral location is associated with survival outcomes in upper tract urothelial carcinoma: A population‐based analysis

Abstract Because population-based risk estimates for metachronous contralateral UTUC are lacking. In this study, we aimed to evaluate the risk and survival of metachronous contralateral upper tract urothelial carcinoma (UTUC) on a large population-based level. A total of 23,075 patients were identified from the Surveillance, Epidemiology, and End Results database (1973–2015), 144 (0.6%) patients developed metachronous contralateral UTUC (median of 32 months after diagnosis). The cumulative incidence at 10, 20, and 30 years of follow-up was 1.1%, 1.6%, and 2.6%, respectively. We applied Fine and Gray’s competing risk regression model to determine the risk factors of a new contralateral, metachronous UTUC. The competing risk regression model demonstrated that older age (hazard ratio [HR] 0.75; 95% CI 0.67–0.85) and larger tumor size (HR 0.61; 95% CI 0.39–0.97) were associated with a significantly decreased risk of metachronous contralateral UTUC. However, bladder cancer presence was an independent risk factor for the development of contralateral tumors (HR 2.42; 95% CI 1.73–3.37). In addition, we demonstrated developing contralateral UTUC was not associated with poor prognosis by using Kaplan–Meier and multivariable analysis. Our findings suggest that metachronous contralateral UTUC is comparatively rare, and has not impact on survival. Importantly, patients with younger age, small tumours, and the presence of bladder cancer were more likely to develop a contralateral tumor, which may provide a rationale for lifelong surveillance in high-risk patients.

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Contemporary use of lymph node dissection at nephroureterectomy in treating upper tract urothelial carcinoma: A US population-based analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.e15634 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. e15634-e15634

Author(s):

Yu-Wei Chen ◽

Francisco Gelpi-Hammerschmidt ◽

Chao-Ping Wu ◽

Joaquim Bellmunt ◽

Steven L. Chang

Keyword(s):

Lymph Node ◽

Urothelial Carcinoma ◽

Lymph Node Dissection ◽

Population Based ◽

Upper Tract Urothelial Carcinoma ◽

Node Dissection ◽

Upper Tract

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Impact of neoadjuvant chemotherapy on pathologic outcomes in patients with upper tract urothelial carcinoma undergoing extirpative surgery.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.457 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 457-457

Author(s):

Nima Almassi ◽

Tianming Gao ◽

Byron Lee ◽

Robert Stein ◽

Georges-Pascal Haber ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Urothelial Carcinoma ◽

Linear Trend ◽

Clinical Stage ◽

Multivariable Analysis ◽

Population Based ◽

Upper Tract Urothelial Carcinoma ◽

Upper Tract ◽

Pathologic Staging ◽

Selection Of

457 Background: Neoadjuvant chemotherapy (NAC) is infrequently administered to patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy or segmental ureterectomy and its impact on pathologic outcomes unclear. We examine pathologic outcomes in patients with UTUC receiving NAC before extirpative surgery using a population-based cancer registry. Methods: Patients who underwent extirpative surgery for UTUC from 2006-2014 were identified from the National Cancer Database. Among patients with available clinicopathologic data, the incidence of pathologic down-staging, defined as a lesser pathologic compared to clinical stage, was compared between patients who did and did not receive NAC. A multivariable model was developed to identify predictors of pathologic down-staging. Results: 7,244 patients were identified with non-metastatic UTUC who underwent extirpative surgery in the study period. 260 patients (3.6%) received NAC, with the use of NAC increasing over time from 2.0% patients in 2006 to 7.1% of patients in 2014 (linear trend p < 0.001). Clinical and pathologic staging data were available for 119 and 2904 patients who did and did not receive NAC, respectively. Thirty patients (25.2%) who received NAC experienced pathologic down-staging, compared to 52 patients (1.8%) who did not receive NAC (p < 0.0001). On multivariable analysis, NAC was associated with a higher likelihood of pathologic down-staging (OR 10.2, 95% CI 5.4-19.3). Additional predictors of pathologic down-staging include a higher clinical T stage (p = 0.001) and African-American race (OR 2.7, 95% CI 1.1-6.6). Compared to renal pelvis UTUC, ureteral UTUC was associated with a similar likelihood of pathologic down-staging (OR 1.5, 95% CI 0.9-2.5). Conclusions: NAC is infrequently used among patients with UTUC undergoing extirpative surgery. A higher incidence of pathologic down-staging was observed among patients receiving NAC. These findings suggest clinical benefit of NAC with respect to pathologic outcomes in patients with UTUC and may help guide selection of patients for NAC prior to radical surgery until data from prospective studies becomes available.

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Expression Analysis and Mutational Status of Histone Methyltransferase KMT2D at Different Upper Tract Urothelial Carcinoma Locations

Journal of Personalized Medicine ◽

10.3390/jpm11111147 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1147

Author(s):

Ekaterina Laukhtina ◽

Ursula Lemberger ◽

Andreas Bruchbacher ◽

Dafina Ilijazi ◽

Stephan Korn ◽

...

Keyword(s):

Bladder Cancer ◽

Protein Expression ◽

Urothelial Carcinoma ◽

Clinical Decision Making ◽

Histone Methyltransferase ◽

Tumor Location ◽

Upper Tract Urothelial Carcinoma ◽

Survival Outcomes ◽

Upper Tract ◽

Mutational Status

The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate KMT2D expression, mutation patterns, and their utility as prognostic biomarkers in patients with UTUC. A single-center study was conducted on tumor specimens from 51 patients treated with radical nephroureterectomy (RNU). Analysis of KMT2D protein expression was performed using immunohistochemistry (IHC). Customized next-generation sequencing (NGS) was used to assess alterations in KMT2D exons. Cox regression was used to assess the relationship of KMT2D protein expression and mutational status with survival outcomes. KMT2D expression was increased in patients with a previous history of bladder cancer (25% vs. 0%, p = 0.02). The NGS analysis of KMT2D exons in 27 UTUC tumors revealed a significant association between pathogenic KMT2D variants and tumor location (p = 0.02). Pathogenic KMT2D variants were predominantly found in patients with non-pelvic or multifocal tumors (60% vs. 14%), while the majority of patients with a pelvic tumor location (81% vs. 20%) did not harbor pathogenic KMT2D alterations. Both IHC and NGS analyses of KMT2D failed to detect a statistically significant association between KMT2D protein or KMT2D gene alteration status and clinical variables such as stage/grade of the disease or survival outcomes (all p > 0.05). KMT2D alterations and protein expression were associated with UTUC features such as multifocality, ureteral location, and previous bladder cancer. While KMT2D protein expression and KMT2D mutational status do not seem to have prognostic value in UTUC, they appear to add information to improve clinical decision-making regarding the type of therapy.

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