{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:29:17Z","timestamp":1785414557406,"version":"3.56.0"},"reference-count":72,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"crossref","award":["SUBZ.C090.26.080"],"award-info":[{"award-number":["SUBZ.C090.26.080"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"crossref"}]},{"award":["SUBZ.C090.26.080"],"award-info":[{"award-number":["SUBZ.C090.26.080"]}],"id":[{"id":"https:\/\/ror.org\/01qpw1b93","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Upper tract urothelial carcinoma (UTUC) is a rare malignancy representing approximately 5\u201310% of all urothelial cancers. Key risk factors include smoking, chemical exposures, selected metabolic conditions, and hereditary cancer syndromes. This narrative review summarises current knowledge on UTUC molecular pathogenesis, major risk determinants, and contemporary therapeutic strategies. Methods: This study was conducted as a narrative review with a structured literature search. PubMed, Web of Science, Embase, and Scopus were searched using predefined combinations of UTUC-related terms covering molecular pathogenesis, carcinogenic risk factors, and treatment strategies. The review was prepared according to SANRA principles to improve transparency and consistency; however, no formal systematic review methodology or meta-analysis was performed. Results: Available genomic studies indicate that UTUC has a molecular profile distinct from urothelial bladder carcinoma (UBC), with recurrent alterations involving FGFR3, HRAS, KMT2D, CDKN2A, KRAS, MYC, and BRIP1. Smoking, aristolochic acid exposure, Lynch syndrome, and possibly early-onset urolithiasis contribute to carcinogenesis through distinct but incompletely understood mechanisms. Surgical treatment remains the standard of care for high-risk localised disease, whereas perioperative chemotherapy, immunotherapy, and targeted agents are expanding treatment options, particularly in advanced disease. A substantial proportion of the therapeutic evidence, however, is derived from broader urothelial carcinoma populations rather than UTUC-specific studies. Conclusions: UTUC is biologically heterogeneous and shaped by both molecular alterations and environmental exposures. Although substantial progress has been made, important gaps remain in understanding UTUC-specific carcinogenic mechanisms and in defining evidence-based personalised treatment strategies. Better integration of molecular, environmental, and clinical data is needed to improve risk stratification and treatment selection.<\/jats:p>","DOI":"10.3390\/cancers18152394","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:49:27Z","timestamp":1785131367000},"page":"2394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Upper Tract Urothelial Carcinoma: Molecular Pathogenesis and Current Treatment Strategies\u2014A Narrative Review"],"prefix":"10.3390","volume":"18","author":[{"given":"Dominik","family":"Zawadzki","sequence":"first","affiliation":[{"name":"Department of Minimally Invasive and Robotic Urology, University Centre of Excellence in Urology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6201-6735","authenticated-orcid":false,"given":"Natalia","family":"Libergal","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive and Robotic Urology, University Centre of Excellence in Urology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ja\u015bmina","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive and Robotic Urology, University Centre of Excellence in Urology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Grzanka","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive and Robotic Urology, University Centre of Excellence in Urology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8021-2781","authenticated-orcid":false,"given":"Maksymilian","family":"Miko\u0142ajczyk","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive and Robotic Urology, University Centre of Excellence in Urology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2470-7996","authenticated-orcid":false,"given":"Miko\u0142aj","family":"Kisia\u0142a","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive and Robotic Urology, University Centre of Excellence in Urology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Tulski","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive and Robotic Urology, University Centre of Excellence in Urology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Krajewski","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive and Robotic Urology, University Centre of Excellence in Urology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Szyde\u0142ko","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive and Robotic Urology, University Centre of Excellence in Urology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5933-3753","authenticated-orcid":false,"given":"Bartosz","family":"Ma\u0142kiewicz","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive and Robotic Urology, University Centre of Excellence in Urology, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/MOU.0000000000001242","article-title":"Upper Tract Urothelial Carcinoma: Epidemiology, Presentation, and High-Risk Endemic Populations","volume":"35","author":"Clark","year":"2025","journal-title":"Curr. Opin. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00345-016-1928-x","article-title":"Epide-miology, Diagnosis, Preoperative Evaluation and Prognostic Assessment of Upper-Tract Urothelial Carcinoma (UTUC)","volume":"35","author":"Soria","year":"2017","journal-title":"World J. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.ccell.2021.05.008","article-title":"Molecular Classification and Diagnostics of Upper Urinary Tract Urothelial Carcinoma","volume":"39","author":"Fujii","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e000126","DOI":"10.1136\/esmoopen-2016-000126","article-title":"Upper Tract Urothelial Carcinoma: A Different Disease Entity in Terms of Management","volume":"1","author":"Leow","year":"2016","journal-title":"ESMO Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e240056","DOI":"10.1148\/rg.240056","article-title":"Imaging of Upper Tract Urothelial Carcinoma","volume":"44","author":"Nakai","year":"2024","journal-title":"Radiographics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/PAP.0000000000000421","article-title":"Contemporary Issues in Urothelial Carcinoma of Upper Urinary Tract","volume":"31","author":"Zhao","year":"2024","journal-title":"Adv. Anat. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.taap.2012.11.005","article-title":"The Effect of Cigarette Smoke and Arsenic Exposure on Urothelial Carcinoma Risk Is Modified by Glutathione S-Transferase M1 Gene Null Genotype","volume":"266","author":"Chung","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Huang, J., Pang, W.S., Fung, Y.C., Mak, F.Y., Chan, S.C., Liu, X., Zhang, L., Lucero-Prisno, D.E., Xu, W., and Zheng, Z.J. (2024). Global Burden, Risk Factors, and Temporal Trends of Ureteral Cancer: A Comprehensive Analysis of Cancer Registries. BMC Med., 22.","DOI":"10.1186\/s12916-024-03485-x"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.eururo.2025.02.023","article-title":"European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: Summary of the 2025 Update","volume":"87","author":"Birtle","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ghoreifi, A., Sari Motlagh, R., and Fuchs, G. (2023). Modern Kidney-Sparing Management of Upper Tract Urothelial Carcinoma. Cancers, 15.","DOI":"10.3390\/cancers15184495"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s11912-021-01179-8","article-title":"Management of Upper Tract Urothelial Carcinoma","volume":"24","author":"Shvero","year":"2022","journal-title":"Curr. Oncol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Escobar, D., Wang, C., Suboc, N., D\u2019Souza, A., and Tulpule, V. (2025). Diagnosis and Management of Upper Tract Urothelial Carcinoma: A Review. Cancers, 17.","DOI":"10.3390\/cancers17152467"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Carbunaru, S., Rich, J.M., and Murray, K.S. (2025). Adjuvant Chemotherapy and Immunotherapy in Upper Tract Urothelial Carcinoma: Where Do We Stand?. Cancers, 17.","DOI":"10.3390\/cancers17193226"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kanaan, M.R., Schmitz, J., Braesen, J.H., Kuczyk, M.A., and Tezval, H. (2025). Comparison of Molecular Profiles (Nectin-4 and TROP-2) in Upper Tract Urothelial Carcinoma with a Positive History of Urinary Bladder Cancer vs. UTUC Only in the Era of ADCs. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-15042-7"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4660","DOI":"10.1097\/JS9.0000000000001479","article-title":"Comparative Investigation of Neoadjuvant Immuno-therapy versus Adjuvant Immunotherapy in Perioperative Patients with Cancer: A Global-Scale, Cross-Sectional, and Large-Sample Informatics Study","volume":"110","author":"Guo","year":"2024","journal-title":"Int. J. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41073-019-0064-8","article-title":"SANRA\u2014A Scale for the Quality Assessment of Narrative Review Articles","volume":"4","author":"Baethge","year":"2019","journal-title":"Res. Integr. Peer Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"636","DOI":"10.21037\/tau.2016.03.23","article-title":"Why Are Upper Tract Urothelial Carcinoma Two Different Diseases?","volume":"5","author":"Szarvas","year":"2016","journal-title":"Transl. Androl. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1038\/s41467-019-10873-y","article-title":"Upper Tract Urothelial Carcinoma Has a Luminal-Papillary T-Cell Depleted Contexture and Activated FGFR3 Signaling","volume":"10","author":"Robinson","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4520","DOI":"10.1200\/JCO.2024.42.16_suppl.4520","article-title":"Comparing the Somatic, Germline, and Immune Landscapes of Upper Tract Urothelial Carcinoma (UTUC) and UC of the Bladder (UCB)","volume":"42","author":"Yuen","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1158\/1078-0432.CCR-18-2039","article-title":"Clonal Relatedness and Mutational Differences between Upper Tract and Bladder Urothelial Carcinoma","volume":"25","author":"Audenet","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"697","DOI":"10.7150\/jca.28494","article-title":"Multi-Omics Perspective on the Tumor Microenvironment Based on PD-L1 and CD8 T-Cell Infiltration in Urothelial Cancer","volume":"10","author":"Chen","year":"2019","journal-title":"J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.juro.2011.10.038","article-title":"Genetic Variability in 8q24 Confers Suscep-tibility to Urothelial Carcinoma of the Upper Urinary Tract and Is Linked with Patterns of Disease Aggressiveness at Diagnosis","volume":"187","author":"Drouin","year":"2012","journal-title":"J. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1111\/j.1349-7006.2006.00264.x","article-title":"Development and Progression of Urothelial Carcinoma","volume":"97","author":"Kakizoe","year":"2006","journal-title":"Cancer Sci."},{"key":"ref_24","first-page":"590","article-title":"Synchronous and Metachronous Urothelial Carcinoma of the Upper Urinary Tract and the Bladder: Are They Clonally Related? A Systematic Review","volume":"38","author":"Aben","year":"2020","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1056\/NEJM199203123261104","article-title":"Clonal Origin of Bladder Cancer","volume":"326","author":"Sidransky","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1097\/00005392-200102000-00092","article-title":"Distinct Microsatellite Alterations in Upper Urinary Tract Tumors and Subsequent Bladder Tumors","volume":"165","author":"Takahashi","year":"2001","journal-title":"J. Urol."},{"key":"ref_27","first-page":"428","article-title":"P53 Mutations in Multiple Urothelial Carcinomas: A Molecular Analysis of the Development of Multiple Carcinomas","volume":"10","author":"Goto","year":"1997","journal-title":"Mod. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.mrrev.2004.02.001","article-title":"Genotoxicity of Tobacco Smoke and Tobacco Smoke Condensate: A Review","volume":"567","author":"DeMarini","year":"2004","journal-title":"Mutat. Res. Mutat. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/iju.13376","article-title":"Epidemiology of Urothelial Carcinoma","volume":"24","author":"Miyazaki","year":"2017","journal-title":"Int. J. Urol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/1097-0142(20000801)89:3<630::AID-CNCR19>3.0.CO;2-Q","article-title":"The Impact of Characteristics of Cigarette Smoking on Urinary Tract Cancer Risk: A Meta-Analysis of Epidemiologic Studies","volume":"89","author":"Zeegers","year":"2000","journal-title":"Cancer"},{"key":"ref_31","first-page":"1119","article-title":"Changing Cigarette Habits and Bladder Cancer Risk: A Case-Control Study","volume":"78","author":"Hartge","year":"1987","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.eururo.2017.07.036","article-title":"European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2017 Update","volume":"73","author":"Babjuk","year":"2018","journal-title":"Eur. Urol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/bju.12014","article-title":"Gender-Specific Effect of Smoking on Upper Tract Urothelial Carcinoma Outcomes","volume":"112","author":"Rink","year":"2013","journal-title":"BJU Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.eururo.2012.06.029","article-title":"Impact of Smoking on Oncologic Outcomes of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy","volume":"63","author":"Rink","year":"2013","journal-title":"Eur. Urol."},{"key":"ref_35","first-page":"330.e9","article-title":"Cumulative Smoking Exposure Impacts Oncologic Outcomes of Upper Tract Urothelial Carcinoma","volume":"43","author":"Bhanvadia","year":"2025","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Alouini, S. (2024). Risk Factors Associated with Urothelial Bladder Cancer. Int. J. Environ. Res. Public Health, 21.","DOI":"10.3390\/ijerph21070954"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1096\/fj.12-227074","article-title":"Genotoxicity of Tobacco Smoke-Derived Aromatic Amines and Bladder Cancer: Current State of Knowledge and Future Research Directions","volume":"27","author":"Besaratinia","year":"2013","journal-title":"FASEB J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1111\/j.1464-410X.2009.08341.x","article-title":"Smoking and Urological Disease","volume":"103","author":"Crow","year":"2009","journal-title":"BJU Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/bju.12400","article-title":"Impact of Smoking Status and Cumulative Exposure on Intravesical Recurrence of Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy","volume":"114","author":"Xylinas","year":"2014","journal-title":"BJU Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"287","DOI":"10.3892\/mco.2014.471","article-title":"Smoking-Induced Changes in Cancer-Related Factors in Patients with Upper Tract Urothelial Cancer","volume":"3","author":"Miyata","year":"2015","journal-title":"Mol. Clin. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s00345-023-04406-y","article-title":"Impact of Smoking on Urologic Cancers: A Snapshot of Current Evidence","volume":"41","author":"Kumar","year":"2023","journal-title":"World J. Urol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.mrgentox.2011.11.015","article-title":"Tissue-Specific Mutagenesis by N-Butyl-N-(4-Hydroxybutyl)Nitrosamine as the Basis for Urothelial Carcinogenesis","volume":"742","author":"He","year":"2012","journal-title":"Mutat. Res.-Genet. Toxicol. Environ. Mutagen."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1158\/1557-3265.BLADDER19-B20","article-title":"Characterization of Tumor Mutational Landscape in Smokers and Nonsmokers with Urothelial Carcinoma","volume":"26","author":"Walasek","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1038\/s12276-020-00529-z","article-title":"Small but Mighty: The Causes and Consequences of Micronucleus Rupture","volume":"52","author":"Kwon","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1093\/mutage\/10.4.329","article-title":"The Micronucleus Assay in Human Exfoliated Urothelial Cells: Effect of Smoking","volume":"10","author":"Amara","year":"1995","journal-title":"Mutagenesis"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"17562872251352049","DOI":"10.1177\/17562872251352049","article-title":"de la Impact of Smoking Status at Diagnosis on Oncological Outcomes of Upper-Tract Urothelial Carcinoma","volume":"17","author":"Zhao","year":"2025","journal-title":"Ther. Adv. Urol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.purol.2014.06.012","article-title":"[Epidemiology and risk factors of upper urinary tract tumors: Liter-ature review for the yearly scientific report of the French National Association of Urology]","volume":"24","author":"Ouzzane","year":"2014","journal-title":"Prog. Urol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.1016\/S1569-9056(14)60043-9","article-title":"Genome-Wide Mutational Signatures of Aristolochic Acid in Urothelial Cancer","volume":"13","author":"Poon","year":"2014","journal-title":"Eur. Urol. Suppl."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Chen, I.-H., Luo, H.-L., Su, Y.-L., Huang, C.-C., Chiang, P.-H., Yu, C.-C., Lee, N.-L., Lin, J.-J., and Sung, M.-T. (2019). Aristolochic Acid Affects Upper Tract Urothelial Cancer Behavior through the MAPK Pathway. Molecules, 24.","DOI":"10.3390\/molecules24203707"},{"key":"ref_50","first-page":"e1\u2013e523-523.e7","article-title":"Insights of Stone-Induced Carcinogenesis of the Urinary Tract through Biopsies of Renal Pelvic Lesions during Lithotomy","volume":"43","author":"Wang","year":"2025","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.purol.2009.10.010","article-title":"Tumeurs des voies excr\u00e9trices uri-naires sup\u00e9rieures sporadiques: Identification de l\u2019interaction entre l\u2019exposition aux carcinog\u00e8nes environnementaux et la susceptibilit\u00e9 g\u00e9n\u00e9tique des individus","volume":"20","author":"Colin","year":"2010","journal-title":"Prog. Urol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Chagneau, C.V., Massip, C., Bossuet-Greif, N., Fremez, C., Motta, J.-P., Shima, A., Besson, C., Faouder, P.L., C\u00e9nac, N., and Roth, M.-P. (2021). Uropathogenic E. coli Induces DNA Damage in the Bladder. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009310"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41416-018-0356-7","article-title":"Kidney Stones and the Risk of Renal Cell Carcinoma and Upper Tract Urothelial Carcinoma: The Netherlands Cohort Study","volume":"120","author":"Schouten","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_54","first-page":"353","article-title":"Universal Lynch Syndrome Screening Should Be Performed in Upper Tract Urothelial Carcinomas","volume":"98","author":"Ju","year":"2018","journal-title":"Lab. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/MOU.0000000000000340","article-title":"Lynch Syndrome in Upper Tract Urothelial Carcinoma: Significance, Screening, and Sur-veillance","volume":"27","author":"Pradere","year":"2017","journal-title":"Curr. Opin. Urol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"467","DOI":"10.2147\/CMAR.S445529","article-title":"Upper Tract Urothelial Carcinoma (UTUC): Prevalence, Impact and Management Challenge","volume":"16","author":"Nally","year":"2024","journal-title":"Cancer Manag. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Head, D.J., and Raman, J.D. (2024). Kidney-Sparing Surgery for Upper Tract Urothelial Carcinoma\u2014Modalities, Outcomes, and Limita-tions. J. Clin. Med., 13.","DOI":"10.3390\/jcm13216593"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/OTT.S225301","article-title":"Optimal Management of Upper Tract Urothelial Carcinoma: Current Perspectives","volume":"13","author":"Leow","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Yang, H.-Y., Yang, C.-C., Wu, C.-Y., Wang, L.-J., and Lu, K.-L. (2019). Aristolochic Acid and Immunotherapy for Urothelial Carcinoma: Directions for Unmet Needs. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133162"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.21037\/tau-22-457","article-title":"Comparison of Molecular Profiles of Upper Tract Urothelial Carcinoma vs. Urinary Bladder Cancer in the Era of Targeted Therapy: A Narrative Review","volume":"11","author":"Tomiyama","year":"2022","journal-title":"Transl. Androl. Urol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"687","DOI":"10.3390\/curroncol29020060","article-title":"Current Advances in Immune Checkpoint Inhibition and Clinical Genomics in Upper Tract Urothelial Carcinoma: State of the Art","volume":"29","author":"Califano","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1056\/NEJMoa2034442","article-title":"Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma","volume":"384","author":"Bajorin","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1056\/NEJMoa2035807","article-title":"Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma","volume":"384","author":"Powles","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Thouvenin, J., Mart\u00ednez Chanz\u00e1, N., Alhalabi, O., Lang, H., Tannir, N.M., Barth\u00e9l\u00e9my, P., and Malouf, G.G. (2021). Efficacy of Immune Checkpoint Inhibitors in Upper Tract Urothelial Carcinomas: Current Knowledge and Future Directions. Cancers, 13.","DOI":"10.3390\/cancers13174341"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.21037\/tau-21-47","article-title":"Update on Systemic Treatment of Upper Tract Urothelial Carcinoma: A Narrative Review of the Literature","volume":"10","author":"Gust","year":"2021","journal-title":"Transl. Androl. Urol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Albers Acosta, E., Subiela, J.D., Pelari-Mici, L., Saavedra Centeno, M., L\u00f3pez-Fando Lavalle, L., Toquero Diez, P., Romero-Laorden, N., Pichler, R., Scilipoti, P., and San-Jos\u00e9 Manso, L. (2026). Perioperative Management of Upper Tract Urothelial Car-cinoma: Current Evidence and Future Directions. Urol. Int., 1\u201323.","DOI":"10.1159\/000551611"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Padull\u00e9s, B., Carrasco, R., Ingelmo-Torres, M., Rold\u00e1n, F.L., G\u00f3mez, A., V\u00e9lez, E., Alfambra, H., Figueras, M., Carrion, A., and Gil-Vernet, J. (2024). Prognostic Value of Liquid-Biopsy-Based Biomarkers in Upper Tract Urothelial Carcinoma. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073695"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.2217\/fon-2021-1629","article-title":"Targeting FGFR3 Alterations with Adjuvant Infigratinib in Invasive Urothelial Carcinoma: The Phase III PROOF 302 Trial","volume":"18","author":"Pal","year":"2022","journal-title":"Future Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.7150\/thno.94788","article-title":"Theranostics and Artificial Intelligence: New Frontiers in Personalized Medicine","volume":"14","author":"Bilgin","year":"2024","journal-title":"Theranostics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"497","DOI":"10.21037\/tau-22-641","article-title":"The Utility of Clinical Registries for Guiding Clinical Practice in Upper Tract Urothelial Cancer: A Narrative Review","volume":"12","author":"Kealey","year":"2023","journal-title":"Transl. Androl. Urol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.eururo.2024.10.024","article-title":"Molecular Heterogeneity and Immune Infiltration Drive Clinical Outcomes in Upper Tract Urothelial Carcinoma","volume":"87","author":"Kim","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.csbj.2021.01.009","article-title":"Multi-Omics Approaches in Cancer Research with Applications in Tumor Subtyping, Prognosis, and Diagnosis","volume":"19","year":"2021","journal-title":"Comput. Struct. Biotechnol. 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