Update on systemic treatment of upper tract urothelial carcinoma: a narrative review of the literature.
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ABSTRACT:
SUBMITTER: Gust KM
PROVIDER: S-EPMC8575594 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as
| S-EPMC7161362 | biostudies-literature
Project description:Urothelial carcinomas (UC) arise from the urothelium that covers the proximal urethra, urinary bladder, and the upper urinary tract. In daily routine and clinical trials UC originating from different locations are often treated and investigated in the same manner. However, differences between the two locations seem to be apparent and may question in handling them as a single oncologic entity. In this review we discuss similarities and differences between bladder and upper urinary tract UC and consider their potential impact on treatment strategies. Despite similarities of UC in the bladder (BC) and the upper urinary tract (UTUC), clinicopathologic and molecular differences may question to generally assemble both as a single tumor entity. Treatment standards for UTUC are often adopted from BC. However, a specific investigation in the former may still be meaningful as shown by the example of adjuvant cisplatin based chemotherapy. In conclusion, future investigations should prioritize the understanding of the tumor biology of both BC and UTUC. This may reveal which UTUC can be treated according to treatment standards of BC and in which cases, a separate approach may be more appropriate.
| S-EPMC8575564 | biostudies-literature
Project description:Infiltrating urothelial carcinoma sarcomatoid variant is a rare variant of urothelial carcinoma. We report a case of a 68-year-old female with a history of hematuria. CT scan with contrast showed a mass in the 1/3 distal of the right ureter. The biopsy result showed a high-grade infiltrating urothelial carcinoma. A radical nephroureterectomy was performed but at the follow-up after 3 months, there was a recurrent mass and gemcitabine-cisplatin chemotherapy was given. Since a high-grade infiltrating urothelial carcinoma sarcomatoid variant was an aggressive tumor, we need to give more attention to evaluating this tumor.
| S-EPMC10176196 | biostudies-literature
Project description:Upper tract urothelial carcinoma comprises 5-10% of all urothelial carcinoma cases. This disease tends to have a more aggressive course than its lower urinary tract counterpart, with 60% of patients presenting with invasive disease and 30% of patients presenting with metastatic disease at diagnosis. The diagnostic workup of UTUC involves imaging with CT urogram, urine cytology, and direct visualization and biopsy of suspected lesions via ureteroscopy. Standard treatment of high-grade UTUC involves radical nephroureterectomy (RNU) and excision of the ipsilateral bladder cuff. Both the NCCN and EAU Guidelines include neoadjuvant chemotherapy as a treatment option for select patients with UTUC; however, there are no strict guidelines. Much of the rationale for neoadjuvant chemotherapy is based on extrapolation from data from muscle-invasive bladder cancer, which has demonstrated a 5-year OS benefit of 5-8%. Retrospective studies evaluating the use of NACT in urothelial carcinoma have yielded pathologic objective response rates of 48% in UTUC cohorts. The randomized Phase III POUT study noted a DFS advantage with adjuvant platinum-based chemotherapy, compared with surveillance in UTUC, of 70% vs. 51% at 2 years. Though not the standard of care, multiple studies have explored the use of perioperative immunotherapy or chemoimmunotherapy in the management of invasive urothelial carcinoma. The PURE-02 study explored the use of neoadjuvant pembrolizumab in patients with high-risk UTUC. A small study of 10 patients, it showed no significant signals of activity with neoadjuvant pembrolizumab. Another Phase II study of neoadjuvant ipilimumab and nivolumab in cisplatin-ineligible UTUC yielded more promising findings, with 3/9 patients attaining a pathologic CR and the remaining six pathologically downstaged. The ABACUS trial found a 31% pathologic complete response rate amongst cisplatin-ineligible MIBC patients treated with neoadjuvant atezolizumab. The use of adjuvant immunotherapy has been explored over three phase III trials. The CheckMate-274 trial found a DFS benefit with the addition of one year of adjuvant nivolumab in patients with high-risk urothelial carcinoma. The IMvigor-010 study of adjuvant atezolizumab was a negative study. The AMBASSADOR trial of adjuvant pembrolizumab is pending results. With the FDA approval of erdafitinib in metastatic urothelial carcinoma, similar targets have been explored for use in perioperative use in invasive urothelial carcinoma, as with adjuvant infigratinib in the PROOF-302 trial. As the treatment paradigm for urothelial carcinoma evolves, further prospective studies are needed to expand the perioperative treatment landscape of UTUC.
| S-EPMC10571968 | biostudies-literature
Project description:Purpose of reviewUpper 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 findingsURS 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.
| S-EPMC8497313 | biostudies-literature
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.
| S-EPMC6777567 | biostudies-literature
Project description:ObjectiveTo perform a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, investigating the role of lymph node dissection (LND) during nephroureterectomy (NU) for upper tract urothelial carcinoma (UTUC); focussing on survival and complication outcomes.MethodsA comprehensive systematic search was completed using a combination of Medical Subject Headings terms and keywords related to UTUC and LND on multiple databases. Meta-analyses were performed when outcomes were reported under the same definition in two or more studies. Where meta-analysis was not possible, outcomes were reviewed in a narrative manner.ResultsA total of 21 studies were included in the qualitative analysis and 11 cohort studies in the quantitative analysis. Our review did not detect significant improvement in recurrence-free survival (RFS) (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.41-1.92), cancer-specific survival (CSS) (HR 0.89, 95% CI 0.54-1.46) and overall survival (OS) (HR 1.10, 95% CI 0.93-1.30). However, when focussing on studies only including patients with pT2/pT3 UTUC, not performing LND significantly worsened RFS (HR 2.83, 95% CI 1.72-4.66). Reports of removing more than eight lymph nodes may also provide prognostic benefits in pN0 patients. The performance of LND was not associated with a higher rate of postoperative complications (risk ratio 1.06, 95% CI 1.00-1.13).ConclusionOverall, LND did not provide additional benefit in RFS, CSS and OS. However, there was a potential benefit in RFS in patients with muscle-invasive and advanced UTUC. LND was also not associated with increased risks of postoperative complications.Abbreviations: CIS: carcinoma in situ; CSS: cancer-specific survival; HR: hazard ratio; LND: lymph node dissection; NU: nephroureterectomy; OS: overall survival; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RFS: recurrence-free survival; RoB, risk of bias; RR: risk ratio; (UT)UC: (upper tract) urothelial carcinoma.
| S-EPMC7954472 | 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 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.
| S-EPMC8599752 | biostudies-literature
Project description:BackgroundUpper tract urothelial carcinoma (UTUC) is a rare urological cancer that is still an important public health concern in many areas around the world. Although UTUC has been linked to a number of risk factors, to our knowledge no systematic review has been published on the overall incidence and prevalence of de-novo UTUC. This review aimed to examine the global epidemiology of UTUC to provide clinicians and public health specialists a better understanding of UTUC.MethodsA systematic search was conducted on MEDLINE, Embase, and the Web of Science using a detailed search strategy. Observational epidemiological studies describing the incidence and prevalence of de-novo UTUC in adults were included, and the Joanna Briggs Institute checklist was used for critical appraisal and data extraction of the studies selected.ResultsThe systematic search identified 3506 papers, of which 59 papers were included for qualitative synthesis. The studies selected included data ranging from the years 1943 to 2018. A comprehensive qualitative synthesis of the data was performed. UTUC incidence generally varied according to age (higher with increasing age), sex (unclear), race (unclear), calendar time (increased, stable, or decreased according to region), geographical region (higher in Asian countries), occupation (higher in seamen and printers), and other population characteristics. Prevalence was only reported by one study, which showed UTUC to have the highest incidence of the rare urogenital cancers in Europe.ConclusionThis systematic review highlights an increased incidence of UTUC in certain groups, including increasing age and certain occupations such as seamen. The incidence of UTUC also varies between certain geographical regions. The trend of UTUC incidence for sex, race, and calendar time is less clear due to a wide variety of metrics used by the studies identified. More studies are also required on the prevalence of UTUC to understand its disease burden. Trial registration This review was registered on PROSPERO (registration number CRD42019134255).
| S-EPMC8369798 | biostudies-literature