Upper tract urothelial carcinoma: a different disease entity in terms of management.
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ABSTRACT:
SUBMITTER: Leow JJ
PROVIDER: S-EPMC5419214 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
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Upper tract urothelial carcinoma: a different disease entity in terms of management.
Leow Jeffrey J JJ Chong Kian Tai KT Chang Steven L SL Bellmunt Joaquim J
ESMO open 20160101 6
Upper tract urothelial carcinomas (UTUCs) consist of 5%-10% of all urothelial carcinomas, the rest being urothelial carcinomas of the bladder (UCB). There is increasing evidence to show that UTUC is a distinct disease entity from UCB based on phenotypical and genotypical (genetic and epigenetic) differences. This may account for why the natural history of UTUC is different from that of UCB, with >60% of UTUCs and only 15%-25% of UCB presenting with invasion at diagnosis. Management of UTUC is th ...[more]
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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
Project description:IntroductionUpper tract urothelial carcinoma (UTUC) is a relatively uncommon urologic malignancy for which there has not been significant improvement in survival over the past few decades, highlighting the need for optimal multi-modality management.MethodsA non-systematic review of the latest literature was performed to include relevant articles up to June 2019. It summarizes the epidemiologic risk factors associated with UTUC, including smoking, carcinogenic aromatic amines, arsenic, aristolochic acid, and Lynch syndrome. Molecular pathways underlying UTUC and potential druggable targets are outlined.ResultsSurgical management for UTUC includes kidney-sparing surgery (KSS) for low-risk disease and radical nephroureterectomy (RNU) for high-risk disease. Endoscopic management of UTUC may include ureteroscopic or percutaneous resection. Topical instillation therapy post-KSS aims to reduce recurrence, progression and to treat carcinoma-in-situ; this may be achieved retrogradely (via ureteric catheterization), antegradely (via percutaneous nephrostomy) or via reflux through double-J stent. RNU, which may be performed via open, laparoscopic or robot-assisted approaches, is the gold standard treatment for high-risk UTUC. The distal cuff may be dealt with extravesical, transvesical or endoscopic techniques. Peri-operative chemotherapy and immunotherapy are increasingly utilized; level 1 evidence exists for adjuvant chemotherapy, but neoadjuvant chemotherapy is favored as kidney function is better prior to RNU. Immunotherapy is primarily reserved for metastatic UTUC but is currently being investigated in the perioperative setting.ConclusionThe optimal management of UTUC includes a firm understanding of the epidemiological factors and molecular pathways. Surgical management includes KSS for low-risk disease and RNU for high-risk disease. Peri-operative immunotherapy and chemotherapy may be considered as evidence mounts.
| S-EPMC6954076 | biostudies-literature
Project description:Despite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) tumors have distinct epidemiologic and clinicopathologic differences.To investigate whether the differences between UTUC and UCB result from intrinsic biological diversity.Tumor 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.We 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).Comparison 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.High-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.Comparison 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:Upper-tract urothelial carcinoma (UTUC) is a rare disease, posing many challenges for the treating physician due to the lack of strong evidence-based recommendations. However, novel molecular discoveries and a better understanding of the clinical behavior of the disease lead to a continuous evolution of therapeutic landscape in UTUC. The aim of the review is to provide a comprehensive update of the current diagnostic modalities and treatment strategies in UTUC with a special focus on recent developments and challenges. A comprehensive literature search including relevant articles up to August 2020 was performed using the MEDLINE/PubMed database. Despite several technological improvements, accurate staging and outcome prediction remain major challenges and hamper appropriate risk stratification. Kidney-sparing surgery can be offered in low risk UTUC; however, physician and patient must be aware of the high rate of recurrence and risk of progression due to tumor biology and understaging. The value and efficacy of intracavitary therapy in patients with UTUC remains unclear due to the lack of high-quality data. In high-risk diseases, radical nephroureterectomy with bladder cuff excision and template lymph node dissection is the standard of care. Perioperative systemic chemotherapy is today accepted as a novel standard for advanced cancers. In metastatic or unresectable disease, the therapeutic landscape is rapidly changing due to several novel agents, such as checkpoint inhibitors. While several diagnostic and treatment challenges remain, progress in endoscopic technology and molecular knowledge have ushered a new age in personalized management of UTUC. Novel accurate molecular and imaging biomarkers are, however, still needed to guide decision making as tissue acquisition remains suboptimal. Next generation sequencing and novel agents are promising to rapidly improve patient outcomes.
| S-EPMC8057353 | 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:PurposeMicropapillary variant upper tract urothelial cancer (MP-UTUC) is a rare malignancy with little known regarding its clinical course and/or optimal treatment. In this case series, we describe patient characteristics, surgical treatment, oncologic outcomes, and response to perioperative chemotherapy.Materials and methodsWe conducted a review to identify patients with MP-UTUC treated at our center between January 1994 and October 2017. Clinicopathologic data was obtained. Descriptive statistics, Kaplan-Meier analysis, Cox proportional hazards, and nearest neighbor matching were used to examine the cohort.ResultsEighteen, (4.3%) of 416 patients were found to have MP-UTUC at our institution over a 23-year period. The majority of patients had ≥pT3 disease at the time of extirpative surgery (13/18, 72%) and one was identified as MP-UTUC prior to surgery. Seven patients received neoadjuvant chemotherapy and six patients received adjuvant chemotherapy. Median overall, cancer specific, and recurrence free survival were 3.29, 3.29, and 1.69 years, respectively for MP-UTUC. There was no survival difference between conventional UTUC and MP-UTUC when matched for age, stage, grade, lymphovascular invasion, and margins (HR 1.18, P = 0.567). No MP-UTUC patients receiving neoadjuvant and adjuvant chemotherapy had apparent pathologic down staging, and of those receiving adjuvant chemotherapy two-thirds died of disease within 2 years.ConclusionsMP-UTUC is a rare, and in most cases aggressive malignancy that commonly presents as locally advanced disease. In this case series, MP-UTUC does not appear to respond to perioperative chemotherapy as neoadjuvant and adjuvant chemotherapy did not result in apparent pathologic down staging and the majority of those receiving adjuvant chemotherapy died from MP-UTUC.
| S-EPMC6511295 | biostudies-literature
Project description:BackgroundDifferent genomic characterization in urothelial carcinoma (UC) by site of origin may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether differences between upper tract UC (UTUC) and UC of the bladder (UCB) result from intrinsic biological diversity.Materials and methodsWe prospectively sequenced 118 tumors and matched blood DNA from Chinese patients with UC using next-generation sequencing techniques, including 45 UTUC and 73 UCB. Two hundred twenty-six patients with UTUC and 350 patients with UCB for The Cancer Genome Atlas were acquired from the cbioportal.ResultsThere were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid was only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared with UCB, UTUC had higher clonal and subclonal mutation numbers. TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. Patients with UTUC had lower PD-L1 than those with UCB. There was no significant difference in the number of DDR mutations, copy number variation counts, and tumor mutational burden between UTUC and UCB.ConclusionUTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may imply the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB.Implications for practiceThis study's findings lay the foundation for a deeper understanding of distinct molecular mechanisms and similar treatment opportunities between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) and had important implications for the site-specific management of patients with urothelial carcinoma. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.
| S-EPMC8342585 | biostudies-literature
Project description:Our aim was to analyze the clinical and survival differences among patients who underwent the two main treatment modalities, endoscopic ablation and radical nephroureterectomy. This study examined all patients who had undergone endoscopic management and RNU between Jul. 1988 and Mar. 2019 from the Taiwan UTUC registry. The inclusion criteria were low stage UTUC in RNU and all cases in endoscopic managed UTUC with a curative intent. The demographic and clinical characteristics were included for analysis. In total, 84 cases in the endoscopic group and 272 cases in the RNU group were enrolled for final analysis. The median follow-up period were 33.5 and 42.0 months in endoscopic and RNU group, respectively (p = 0.082). Comparison of Kaplan-Meier estimated survival curves between groups, the endoscopic group was associated with similar overall survival (OS), cancer specific survival (CSS), and intravesical recurrence free survival (IVRS) but demonstrated inferior disease free survival (DFS) (p = 0.188 for OS, p = 0.493 for CSS and p < 0.001 for DFS). Endoscopic management of UTUC was as safe as RNU in UTUC endemic region.
| S-EPMC7889610 | biostudies-literature
Project description: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.
| S-EPMC8625702 | biostudies-literature
Project description:The aim of this study was to investigate the effect of preoperative anemia on the prognosis of patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).A total of 620 patients with UTUC were retrospectively analyzed. Anemia was decided by preoperatively measured hemoglobin values based on the World Health Organization (WHO) classification. Kaplan-Meier method and Cox proportional hazards regression models were used to analyze the relationship between anemia and survival outcomes. The meta-analysis part was performed according to PRISMA guidelines.The median follow-up was 51 (range: 1-168) months. A total of 246 patients had preoperative anemia in our cohort. Anemia was found to be related to high-grade (P < .001), sessile architecture (P = .001), advanced T stage (P < .001), lymphovascular invasion (LVI) (P = .006), and worse chronic kidney disease (CKD) stage (P = .012). Kaplan-Meier curves revealed that patients with preoperative anemia had worse overall survival (OS), cancer-specific survival (CSS), and disease recurrence-free survival (RFS) (all P < .001). Multivariable Cox analyses found that anemia was an independent predictor of CSS [hazard ratio (HR) 1.719, 95% confidence interval (95% CI): 1.285-2.300], RFS (HR 1.427, 95% CI: 1.114-1.829) and OS (HR 1.756, 95% CI: 1.353-2.279). Among patients without end-stage renal disease (ESRD, n = 614), the anemia was also proved to be associated with worse outcomes in multivariable Cox analysis (OS, HR 1.759, 95% CI: 1.353-2.287; CSS, HR 1.726, 95% CI: 1.289-2.311, and RFS, HR 1.431, 95% CI: 1.117-1.837). Seven studies were included in the meta-analysis, and the pooled results showed that anemia was also related to worse CSS (HR 2.05, 95% CI: 1.73-2.44), RFS (HR 1.57, 95% CI: 1.30-1.90), and OS (HR 1.53, 95% CI: 1.10-2.13), but not related to intravesical recurrence (HR 1.17, 95% CI: 0.75-1.82).Preoperative anemia was proved to be significantly associated with worse oncologic outcomes in patients with UTUC following RNU.
| S-EPMC6155943 | biostudies-literature