Dataset Information

Lymph node dissection for upper tract urothelial carcinoma: A systematic review.

ABSTRACT:

Objective

To 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.

Methods

A 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.

Results

A 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).

Conclusion

Overall, 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.

SUBMITTER: Chan VW

PROVIDER: S-EPMC7954472 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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).

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.