Abstract
Background
Upper tract urothelial carcinomas (UTUCs) arise in the renal pelvis or the ureter,
accounting for approximately 5% of all urothelial carcinomas. Recent years have witnessed
the publication of several studies aimed at assessing the molecular, biologic, and
clinical features of UTUC, reporting that FGFR3 mutations are the most observed genetic aberrations; however, several knowledge gaps
persist in the understanding of the genomic landscape of this genitourinary malignancy
with few treatment options.
Patients and Methods
In the current study, we aimed to comprehensively analyze clinicopathological features
of FGFR3-mutated UTUCs patients in public datasets to increase the current knowledge of the
molecular and biologic profile of UTUC. Data regarding clinical outcomes, mutational
profiles, and copy number alterations in patients affected by UTUC were downloaded
from the cBioPortal for Cancer Genomics Database. UTUC data were available from 4
studies, for a total number of 358 patients; among these, 150 UTUC patients presented
FGFR3 mutations.
Results
The current database analysis of the mutational profile of 150 FGFR3-mutated UTUCs suggested that FGFR3 mutations may represent a prognostic factor in this disease, with a statistically
longer overall survival compared to wild-type patients treated with radical surgery.
In addition, FGFR3 mutations were more frequent in low-grade UTUCs with early-stage disease (pT1, pT2,
and pT3).
Conclusion
Genomic characterization of UTUC is destined to become increasingly important, and
more efforts aimed at implementing UTUC genomics analysis are warranted.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Genitourinary CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- European association of urology guidelines on upper urinary tract urothelial carcinoma: 2017 update.Eur Urol. 2018; 73: 111-122https://doi.org/10.1016/j.eururo.2017.07.036
- European association of urology guidelines on upper urinary tract urothelial carcinoma: 2020 update.Eur Urol. 2021; 79: 62-79https://doi.org/10.1016/j.eururo.2020.05.042
- Therapeutic strategies for upper tract urothelial carcinoma.Expert Rev Anticancer Ther. 2018; 18: 765-774https://doi.org/10.1080/14737140.2018.1481395
- Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC).World J Urol. 2017; 35: 379-387https://doi.org/10.1007/s00345-016-1928-x
- Biological behavior and long-term outcomes of carcinoma in situ in upper urinary tract managed by radical nephroureterectomy.J Urol. 2018; 199: 933-939https://doi.org/10.1016/j.juro.2017.10.019
- Trends of incidence and prognosis of upper tract urothelial carcinoma.Bosn J Basic Med Sci. 2021; 21: 607-619https://doi.org/10.17305/bjbms.2020.5345
- Upper urinary tract tumors: variant histology versus urothelial carcinoma.Clin Genitourin Cancer. 2021; 19: 117-124https://doi.org/10.1016/j.clgc.2020.11.004
- Rates of lymph node invasion and their impact on cancer specific mortality in upper urinary tract urothelial carcinoma.Eur J Surg Oncol. 2019; 45: 1238-1245https://doi.org/10.1016/j.ejso.2018.12.004
- Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial.Lancet. 2020; 395: 1268-1277https://doi.org/10.1016/S0140-6736(20)30415-3
- Genomics in upper tract urothelial carcinoma.Curr Opin Urol. 2017; 27: 35-40https://doi.org/10.1097/MOU.0000000000000341
- Comprehensive genomic profiling of upper-tract and bladder urothelial carcinoma.Eur Urol Focus. 2021; 7: 1339-1346https://doi.org/10.1016/j.euf.2020.08.001
- Comparison of genomic characterization in upper tract urothelial carcinoma and urothelial carcinoma of the bladder.Oncologist. 2021; 26: e1395-e1405https://doi.org/10.1002/onco.13839
- Clonal relatedness and mutational differences between upper tract and bladder urothelial carcinoma.Clin Cancer Res. 2019; 25: 967-976https://doi.org/10.1158/1078-0432.CCR-18-2039
- Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts.Nat Commun. 2020; 11: 1975https://doi.org/10.1038/s41467-020-15885-7
- Comprehensive integrative profiling of upper tract urothelial carcinomas.Genome Biol. 2021; 22: 7https://doi.org/10.1186/s13059-020-02230-w
- Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling.Nat Commun. 2019; 10: 2977https://doi.org/10.1038/s41467-019-10873-y
- Genomic characterization of upper tract urothelial carcinoma.Eur Urol. 2015; 68: 970-977https://doi.org/10.1016/j.eururo.2015.07.039
- Genomic biomarkers for the prediction of stage and prognosis of upper tract urothelial carcinoma.J Urol. 2016; 195: 1684-1689https://doi.org/10.1016/j.juro.2016.01.006
- Comprehensive genomic characterization of upper tract urothelial carcinoma.Eur Urol. 2017; 72: 641-649https://doi.org/10.1016/j.eururo.2017.05.048
- Platinum-based adjuvant chemotherapy for upper tract urothelial carcinoma: a change of paradigm? A meta-analysis of aggregate data.Anticancer Drugs. 2022; 33: e61-e68https://doi.org/10.1097/CAD.0000000000001200
- The challenge of managing bladder cancer and upper tract urothelial carcinoma: a review with treatment recommendations from the spanish oncology genitourinary group (SOGUG).Target Oncol. 2019; 14: 15-32https://doi.org/10.1007/s11523-019-00619-7
Article Info
Publication History
Published online: June 17, 2022
Accepted:
June 13,
2022
Received in revised form:
June 12,
2022
Received:
April 28,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
