Clinical registries in upper tract urothelial carcinoma: commitment to collaboration.
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ABSTRACT:
SUBMITTER: Zeng J
PROVIDER: S-EPMC10406535 | biostudies-literature | 2023 Jul
REPOSITORIES: biostudies-literature
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Clinical registries in upper tract urothelial carcinoma: commitment to collaboration.
Zeng Jiping J Chipollini Juan J
Translational andrology and urology 20230619 7
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Project description:The clinical efficacy of adjuvant chemotherapy in upper tract urothelial carcinoma (UTUC) is unclear. We aimed to assess the therapeutic outcomes of adjuvant chemotherapy in patients with advanced UTUC (pT3-T4) after radical nephroureterectomy (RNU). We retrospectively reviewed the data of 2108 patients from the Taiwan UTUC Collaboration Group between 1988 and 2018. Comprehensive clinical features, pathological characteristics, and survival outcomes were recorded. Univariate and multivariate Cox proportional hazards models were used to evaluate overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Of the 533 patients with advanced UTUC included, 161 (30.2%) received adjuvant chemotherapy. In the multivariate analysis, adjuvant chemotherapy was significantly associated with a reduced risk of overall death (hazard ratio (HR), 0.599; 95% confidence interval (CI), 0.419-0.857; p = 0.005), cancer-specific mortality (HR, 0.598; 95% CI, 0.391-0.914; p = 0.018), and cancer recurrence (HR, 0.456; 95% CI, 0.310-0.673; p < 0.001). The Kaplan-Meier survival analysis revealed that patients receiving adjuvant chemotherapy had significantly better five-year OS (64% vs. 50%, p = 0.002), CSS (70% vs. 62%, p = 0.043), and DFS (60% vs. 48%, p = 0.002) rates compared to those who did not receive adjuvant chemotherapy. In conclusion, adjuvant chemotherapy after RNU had significant therapeutic benefits on OS, CSS, and DFS in advanced UTUC.
| S-EPMC8877034 | biostudies-literature
Project description:Background and objectiveUpper tract urothelial cancer (UTUC) lacks high-quality evidence to appraise current patterns of presentation, diagnosis, treatment and outcomes as a result of disease rarity and patient heterogeneity. Registries may overcome many of the challenges making clinical trials challenging in UTUC and provide answers to many of the clinical questions that afflict UTUC management. In this narrative review we aim to summarise the design of registries that have contributed to the UTUC literature, discuss their strengths and limitations and the future directions of registries in UTUC.MethodsTwo independent reviewers conducted a search of the OVID MEDLINE database from July 2002-July 2022. Included articles were required to be published in peer reviewed journals and use registry-based methodology to report on UTUC. Search was limited by MeSH and key words and was limited to the English language.Key content and findingsOne hundred and forty-four articles were identified and included as reporting on UTUC from a registry-based methodology. Articles utilising registry-based data have substantially increased over the study period with the majority of articles arising from large generalised cancer databases in North America. There has been an increase in UTUC-specific registries in the previous five years that have offered the most granular, complete analysis and these will continue to report in the coming years. The majority of published data assessed epidemiological factors and compared outcomes of treatment modalities with a small proportion of articles focusing on prognostic nomograms and quality of life. Larger cancer registries that contribute the majority of the published analysis are likely subject to significant selection bias when comparing cohorts for treatment analysis and the need for prospective UTUC specific registries is apparent. Future directions include the potential for registry-based randomised controlled trials (RCTs) and clinical quality registries (CQR) that have the ability to change practice and improve care.ConclusionsThe utilisation of registry-based methodology for analysis in UTUC has increased substantially over the last 20 years. In addition to the utilisation of large cancer registries, the creation of UTUC specific registries is likely to contribute the most granular, translatable data in diagnosis and management.
| S-EPMC10080345 | biostudies-literature
Project description:An overview of epidemiological pattern of upper tract urothelial carcinoma (UTUC), including outcome of UTUC over past decades as well as factors responsible for observed epidemiological changes was performed. Gender and racial disparities influencing incidence of UTUC were reviewed. The incidence of multifocal urothelial carcinoma and relation of UTUC to urothelial carcinoma of bladder were examined.
| S-EPMC7475674 | biostudies-literature
Project description:Tumor staging of upper tract urothelial carcinomas (UTUCs) is relatively difficult to assert accurately before surgery. Here, we used copy number (CN) signatures as a tool to explore their clinical significance of molecular stratification in UTUC. CN signatures were extracted by non-negative matrix factorization from the whole-genome sequencing (WGS) data of 90 Chinese UTUC primary tumor samples. A validation UTUC cohort (n = 56) and a cohort from urinary cell-free DNA (cfDNA) of urothelial cancer patients (n = 94) and matched primary tumors were also examined. Survival analyses were measured using the Kaplan-Meier, and Cox regression was used for multivariate analysis. Here, we identified six CN signatures (Sig1-6). Patients with a high contribution of Sig6 (Sig6high) were associated with higher microsatellite instability level and papillary architecture and had a favorable outcome. Patients with a low weighted genome integrity index were associated with positive lymph node and showed the worst outcome. Sig6high was identified to be an independently prognostic factor. The predictive significance of CN signature was identified by a validation UTUC cohort. CN signatures retained great concordance between primary tumor and urinary cfDNA. In conclusion, our results reveal that CN signature assessment for risk stratification is feasible and provides a basis for clinical studies that evaluate therapeutic interventions and prognosis.
| S-EPMC8427613 | biostudies-literature
Project description:BackgroundDespite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) tumors have distinct epidemiologic and clinicopathologic differences.ObjectiveTo investigate whether the differences between UTUC and UCB result from intrinsic biological diversity.Design, setting, and participantsTumor and germline DNA from patients with UTUC (n=83) and UCB (n=102) were analyzed using a custom next-generation sequencing assay to identify somatic mutations and copy number alterations in 300 cancer-associated genes.Outcome measurements and statistical analysisWe described co-mutation patterns and copy number alterations in UTUC. We also compared mutation frequencies in high-grade UTUC (n=59) and high-grade UCB (n=102).Results and limitationsComparison of high-grade UTUC and UCB revealed significant differences in the prevalence of somatic alterations. Genes altered more commonly in high-grade UTUC included FGFR3 (35.6% vs 21.6%; p=0.065), HRAS (13.6% vs 1.0%; p=0.001), and CDKN2B (15.3% vs 3.9%; p=0.016). Genes less frequently mutated in high-grade UTUC included TP53 (25.4% vs 57.8%; p<0.001), RB1 (0.0% vs 18.6%; p<0.001), and ARID1A (13.6% vs 27.5%; p=0.050). Because our assay was restricted to genomic alterations in a targeted panel, rare mutations and epigenetic changes were not analyzed.ConclusionsHigh-grade UTUC tumors display a spectrum of genetic alterations similar to high-grade UCB. However, there were significant differences in the prevalence of several recurrently mutated genes including HRAS, TP53, and RB1. As relevant targeted inhibitors are being developed and tested, these results may have important implications for the site-specific management of patients with urothelial carcinoma.Patient summaryComparison of next-generation sequencing of upper tract urothelial carcinoma (UTUC) with urothelial bladder cancer identified that similar mutations were present in both cancer types but at different frequencies, indicating a potential need for unique management strategies. UTUC tumors were found to have a high rate of mutations that could be targeted with novel therapies.
| S-EPMC4675454 | biostudies-literature
Project description:Trophoblast cell surface antigen 2 (Trop-2, encoded by TACSTD2) is the target protein of sacituzumab govitecan, a novel antibody-drug conjugate for locally advanced or metastatic urothelial carcinoma. However, the expression status of Trop-2 in upper tract urothelial carcinoma (UTUC) remains unclear. We performed immunohistochemical analysis of 99 UTUC samples to evaluate the expression status of Trop-2 in patients with UTUC and analyze its association with clinical outcomes. Trop-2 was positive in 94 of the 99 UTUC samples, and high Trop-2 expression was associated with favorable progression-free survival (PFS) and cancer-specific survival (p = 0.0011, 0.0046). Multivariate analysis identified high Trop-2 expression as an independent predictor of favorable PFS (all cases, p = 0.045; high-risk group (pT3≤ or presence of lymphovascular invasion or lymph node metastasis), p = 0.014). Gene expression analysis using RNA sequencing data from 72 UTUC samples demonstrated the association between high TACSTD2 expression and favorable PFS (all cases, p = 0.069; high-risk group, p = 0.029). In conclusion, we demonstrated that Trop-2 is widely expressed in UTUC. Although high Trop-2 expression was a favorable prognostic factor in UTUC, its widespread expression suggests that sacituzumab govitecan may be effective for a wide range of UTUC.
| S-EPMC9222112 | biostudies-literature
Project description:PurposeIn this study, we aimed to determine the clinicopathologic, radiologic, and molecular significance of the tumor invasiveness to further stratify the patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) who can be treated less aggressively.Materials and methodsClinicopathologic and radiologic characteristics of 166 surgically resected HG UTUC (48 noninvasive, and 118 invasive) cases were evaluated. Six noninvasive UTUC cases with intratumoral tumor grade heterogeneity were selected for whole-exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing was done for validation of the target genes from WES data.ResultsPatients with noninvasive UTUC showed no cancer-specific death with better cancer-specific survival (p < 0.001) and recurrence-free survival (p < 0.001) compared to the patients with invasive UTUC. Compared to the invasive UTUC, noninvasive UTUC was correlated to a low grade (LG) on the preoperative abdominal computed tomography (CT) grading system (p < 0.001), histologic intratumoral tumor grade heterogeneity (p=0.018), discrepancy in preoperative urine cytology diagnosis (p=0.018), and absence of urothelial carcinoma in situ (p < 0.001). WES of the heterogeneous components showed mutually shared HRAS and FGFR3 mutations shared between the HG and LG components. HRAS mutation was associated with the lower grade on preoperative abdominal CT and intratumoral tumor grade heterogeneity (p=0.045 and p < 0.001, respectively), whereas FGFR3 mutation was correlated to the absence of carcinoma in situ (p < 0.001).ConclusionAccording to our comprehensive analysis, HG noninvasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Noninvasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.
| S-EPMC11261206 | biostudies-literature
Project description:Upper urinary tract urothelial carcinomas (UTUCs) are often identified and first treated endoscopically. After proper risk stratification, adjuvant treatment may be recommended. Consequently, as adjuvant therapy becomes more common place in the oncological armamentarium, we seek to better characterize its existing and future therapeutic landscape. In this article, we present an overview of the most up-to-date information about intracavitary instillations as an adjuvant therapy in the context of UTUC. We reviewed the current literature on the epidemiology, disease characteristics, treatment, and outcomes of UTUC with a particularly focus on intraluminal adjuvant therapy for UTUC. This review provides a comprehensive overview of the most recent available data regarding adjuvant therapies used for UTUC. Intraluminal therapy plays an increasingly important role in the management of UTUC. Mitomycin C is the most common adjuvant treatment for UTUC with bacillus Calmette-Guerin (BCG) being utilized to a lesser extent. UGN-101 is a novel topical gel-based therapy that has shown promising results and thus recently garnered Food and Drug Administration (FDA) approval for UTUC. Other treatments such as BCG-IFN, gemcitabine, docetaxel, and drug-eluting stents (DES) may play a future role in UTUC treatment given further research. It is important to caveat that current studies on topical adjuvant treatments demonstrate varying degrees of effectiveness. This is largely due to limited research on UTUC, consisting of small sample sizes, and mostly retrospective experiences. Accordingly, further clinical trials are needed to evaluate the true benefit of these treatments.
| S-EPMC10560344 | biostudies-literature
Project description:Urothelial carcinoma is a highly heterogeneous disease that can arise throughout the entire urothelial lining from the renal pelvis to the proximal urethra. Upper tract urothelial carcinoma (UTUC) is rare, and while it shares many similarities with urothelial carcinoma of bladder (UCB), there are also significant differences between UTUC and UCB regarding clinical management and outcomes. No major advances have been made recently in the development of new systemic therapies for urothelial carcinoma, partly due to the lack of understanding of underlying molecular pathogenetic mechanisms. In the past decade, the emergence of next-generation sequencing has greatly enabled genomic characterization of tumor samples. Researchers are currently exploring a personalized approach to augment traditional clinical decision-making based on genetic alterations. In the present review, we summarize current genomic advances in UTUC and discuss the potential implications of these developments for developing prognostic and predictive biomarkers.
| S-EPMC4823991 | biostudies-literature
Project description:While radical nephroureterectomy (RNU) remains the gold-standard treatment for upper tract urothelial carcinoma (UTUC), a growing volume of literature surrounding endoscopic, organ-sparing procedures has developed over the past few decades. Based on this, endoscopic management of UTUC has gained acceptance as a standard of care approach, particularly among those with low-risk disease or with imperative indications for organ preservation. As a rare disease, however, data is mostly restricted to retrospective single institution series with relatively small numbers. Therefore, comparative outcomes of endoscopic management to RNU remain incompletely defined. Furthermore, the comparative utility of endoscopic approaches (ureteroscopy versus percutaneous resection) and topical therapy following resection lacks prospective analysis. In this article we review the available literature on endoscopic management of UTUC.
| S-EPMC7475653 | biostudies-literature