Role of Ureteroscopy in Treatment of Upper Tract Urothelial Carcinoma.
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ABSTRACT: Purpose of review
Upper tract urothelial carcinoma (UTUC) is uncommon accounting for less than 10% of all urothelial tumours. Ureteroscopic management (URS) is the first line treatment for low-risk disease and has been increasingly utilised due to technological advances and increasing surgical experience. This review looks at patient outcomes relating to URS, emerging technologies and the role of adjuvant intracavitary therapy in the management of UTUC.Recent findings
URS has firmly established itself in the management algorithm for UTUC, and a good body of evidence supports its use for low-risk disease, wherein oncological outcomes are comparable to traditional nephroureterectomy (RNU). Larger tumours can now be managed using URS with a lower morbidity than radical surgery, though with higher associated local recurrence rate and risk of progression to RNU, and as a result, patient selection and close surveillance remains key. There is limited evidence for adjuvant intracavitary therapy (Mitomycin C or BCG) in UTUC although the development of novel polymers and biodegradable stents may improve drug delivery to the upper urinary tract. URS has a clearly defined role in low-risk UTUC, and its use in larger tumours appears to be appropriate in a selected cohort of patients. The efficacy of adjuvant intracavitary therapy is as of yet undetermined, though developments in delivery techniques are promising. Likewise further developments of laser technology are anticipated to further expand the role of URS.
SUBMITTER: Ng Chieng Hin J
PROVIDER: S-EPMC8497313 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeTo review the management of metastatic upper tract urothelial carcinoma (UTUC) including recent advances in targeted and immune therapies as an update to the 2014 joint international consultation on UTUC, co-sponsored by the Société Internationale d'Urologie and International Consultation on Urological Diseases.MethodsA PubMed database search was performed between January 2013 and May 2016 related to the treatment of metastatic UTUC, and 54 studies were selected for inclusion.ResultsThe management of patients with metastatic UTUC is primarily an extrapolation from evidence guiding the management of metastatic urothelial carcinoma of the bladder. The first-line therapy for metastatic UTUC is platinum-based combination chemotherapy. Standard second-line therapies are limited and ineffective. Patients with UTUC who progress following platinum-based chemotherapy are encouraged to participate in clinical trials. Recent advances in genomic profiling present exciting opportunities to guide the use of targeted therapy. Immunotherapy with checkpoint inhibitors has demonstrated extremely promising results. Retrospective studies provide support for post-chemotherapy surgery in appropriately selected patients.ConclusionsThe management of metastatic UTUC requires a multi-disciplinary approach. New insights from genomic profiling using targeted therapies, novel immunotherapies, and surgery represent promising avenues for further therapeutic exploration.
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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.
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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.
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Project description:Upper tract urothelial carcinoma (UTUC) is a heterogeneous disease that presents a clinical management challenge for the urologic surgeon. We assessed treatment patterns, costs, and survival outcomes among patients with nonmetastatic UTUC. We identified 4114 patients diagnosed with nonmetastatic UTUC from 2004 to 2013 in the Survival Epidemiology, and End Results-Medicare population-based database. Patients were stratified into low- or high-risk disease groups. Median total costs from 30 days prior to diagnosis through 365 days after diagnosis were compared between groups. Overall and cancer-specific survival were evaluated using Cox proportional hazards regression. All statistical tests were 2-sided. After risk stratification, 1027 (24.9%) and 3087 (75.0%) patients were classified into low- vs high-risk UTUC groups. Most patients underwent at least 1 surgical intervention (95.1%); 68.4% underwent at least 1 endoscopic intervention. Patients diagnosed with high- vs low-risk UTUC were more likely to undergo nephroureterectomy (83.6% vs 72.0%; P < .001); few patients with low-risk disease were exclusively managed endoscopically (16.9%). At 365 days after diagnosis, costs of care for high- vs low-risk UTUC were statistically significantly higher ($108 520 vs $91 233; median difference $16 704, 95% confidence interval [CI] = $11 619 to $21 778; P < .001). Those with high-risk UTUC had worse cancer-specific and overall survival compared with patients with low-risk UTUC (cancer-specific survival hazard ratio [HR] = 4.14, 95% CI = 3.19 to 5.37; overall survival HR = 1.78, 95% CI = 1.62 to 1.96). UTUC continues to be managed primarily with nephroureterectomy, regardless of risk stratification, and patients with high-risk UTUC have worse overall and cancer-specific survival. Substantial costs are associated with management of low- and high-risk UTUC, with the latter being more costly up to 1 year from diagnosis.
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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.
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Project description:This study investigated the applicability of personalized peptide vaccination (PPV) for patients with metastatic upper tract urothelial cancer (mUTUC) after failure of platinum-based chemotherapy. In this single arm, open-label, phase II clinical trial, patients with mUTUC received PPV at a single institution. Personalized peptide vaccination treatment used a maximum of four peptides chosen from 27 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for six s.c. injections weekly as one cycle. The safety of PPV, as well as its influence on host immunity and effect on overall survival were assessed. Forty-eight patients were enrolled in this study. Personalized peptide vaccinations were well tolerated without severe adverse events. Median survival time was 7.3 months (95% confidence interval [CI], 5.3-13.1) with 13.0 months for patients receiving combined salvage chemotherapy (95% CI, 5.7-17.5) and 4.5 months for patients receiving PPV alone (95% CI, 1.7-10.1) (P = 0.080). Patients with positive CTL responses showed a significantly longer survival than patients with negative CTL responses (hazard ratio, 0.37; 95% CI, 0.16-0.85; P = 0.019). Multivariate Cox regression analysis showed that lower numbers of Bellmunt risk factors and lower levels of B-cell activating factor were significantly associated with favorable overall survival for patients under PPV treatment. This study indicated that PPV for patients with mUTUC after failure of platinum-based chemotherapy induced substantial peptide-specific CTL responses without severe adverse events and has the potential to prolong survival when combined with salvage chemotherapy. UMIN Clinical Trials Registry ID: 000001854.
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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.
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Project description:Purpose:To evaluate the impact of diagnostic ureteroscopy performed before radical nephroureterectomy (RNU) on intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC). Materials and Methods:From May 2003 to December 2018, patients who underwent RNU for UTUC were enrolled and divided into two groups according to whether they underwent preoperative ureteroscopy (Pre-U vs. Non-U). We excluded patients who had a history of bladder cancer and did not receive bladder cuff resection during surgery. Perioperative parameters were compared between the two groups by use of t-tests or chi-square tests. Kaplan-Meier and Cox proportional hazards analyses were used to assess the association between Pre-U and IVR. Results:Of the 453 total patients, 226 patients (49.9%, Pre-U group) had received diagnostic ureteroscopy before RNU, and 227 patients (50.1%, Non-U group) had not. IVR occurred in 99 patients (43.8%) in the Pre-U group and 61 patients (26.9%) in the Non-U group (p=0.001). The median time to recurrence was 107 months. The 5-year IVR-free survival rates were 56.2% and 73.1% in the Pre-U and Non-U groups, respectively (log rank test, p<0.001). Multivariate Cox proportional hazards analysis showed that Pre-U was a significant factor (hazard ratio, 1.413; 95% confidence interval, 1.015-1.965; p=0.040) after adjustment for other factors including tumor stage, location, etc. Conclusions:Preoperative diagnostic ureteroscopy before RNU was a significant factor for IVR. Therefore, we should carefully consider Pre-U before RNU for nonobvious ureteral lesions. These results should be validated in a prospective study.
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