AIMS: The European Association of Urology guideline for upper tract urothelial carcinoma (UTUC) relies on two grading system: 1973 World Health Organization (WHO) and 2004/2016 WHO. No consensus has been made which classification should supersede the other and both are recommended in clinical practice. We hypothesized that one may be superior to the other. METHODS: Newly diagnosed non-metastatic UTUC patients treated with radical nephroureterectomy were abstracted from the Surveillance, Epidemiology, and End Results database (2010-2016). Kaplan-Meier plots and multivariable Cox regression models (CRMs) tested cancer-specific mortality (CSM), according to 1973 WHO (G1 vs. G2 vs. G3) or to 2004/2016 WHO (low-grade vs. high-grade) grading systems. Haegerty's C-index quantified accuracy. RESULTS: Of 4271 patients, according to 1973 WHO grading system, 134 (3.1%) were G1, 436 (10.2%) were G2 and 3701 (86.7%) were G3; while according to 2004/2016 WHO grading system, 508 (11.9%) were low grade vs 3763 (88.1%) high grade. In multivariable CRMs, high grade predicted higher CSM (Hazard ratio: 1.70, p < 0.001). Conversely, neither G2 (p = 0.8) nor G3 (p = 0.1) were independent predictors of worse survival. The multivariable models without consideration of either grading system were 74% accurate in predicting 5-year CSM. Accuracy increased to 76% after either addition of the 1973 WHO or 2004/2016 WHO grade. CONCLUSIONS: From a statistical standpoint, either 1973 WHO or 2004/2016 WHO grading system improves the accuracy of CSM prediction to the same extent. In consequence, other considerations such as intra- and interobserver variability may represent additional metrics to consider in deciding which grading system is better.

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montréal Health Center Montreal QC Canada

Department of Urology 2nd Faculty of Medicine Charles University Prag Czech Republic

Department of Urology and Division of Experimental Oncology URI Urological Research Institute IBCAS San Raffaele Scientific Institute Milan Italy

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology University Hospital Frankfurt Frankfurt am Main Germany

Department of Urology University of Texas Southwestern Dallas TX USA

Departments of Urology Weill Cornell Medical College New York NY USA

Division of Urology Department of Special Surgery Jordan University Hospital The University of Jordan Amman Jordan

Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia

Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany

Urology Unit Department of Neurosciences Reproductive Sciences and Odontostomatology University of Naples Federico 2 Naples Italy

Zobrazit více v PubMed

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. doi: 10.3322/caac.21551. PubMed DOI

Rouprêt M, Babjuk M, Compérat E, et al. European association of urology guidelines on upper urinary tract urothelial carcinoma: 2017 update. Eur Urol. 2018;73(1):111–122. doi: 10.1016/j.eururo.2017.07.036. PubMed DOI

Collà Ruvolo C, Nocera L, Stolzenbach LF, et al. Incidence and survival rates of contemporary patients with invasive upper tract urothelial carcinoma. Eur Urol Oncol. 2020 doi: 10.1016/j.euo.2020.11.005. PubMed DOI

Califano G, Xylinas E. Re: Phase II trial of neoadjuvant systemic chemotherapy followed by extirpative surgery in patients with high grade upper tract urothelial carcinoma. Eur Urol. 2020;78(1):113–114. doi: 10.1016/j.eururo.2020.04.008. PubMed DOI

Califano G, Ouzaid I, Verze P, et al. Immune checkpoint inhibition in upper tract urothelial carcinoma. World J Urol. 2020 doi: 10.1007/s00345-020-03502-7. PubMed DOI

Margulis V, Shariat SF, Matin SF, et al. Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. Cancer. 2009;115(6):1224–1233. doi: 10.1002/cncr.24135. PubMed DOI

Lughezzani G, Burger M, Margulis V, et al. Prognostic factors in upper urinary tract urothelial carcinomas: a comprehensive review of the current literature. Eur Urol. 2012;62(1):100–114. doi: 10.1016/j.eururo.2012.02.030. PubMed DOI

Mbeutcha A, Rouprêt M, Kamat AM, et al. Prognostic factors and predictive tools for upper tract urothelial carcinoma: a systematic review. World J Urol. 2017;35(3):337–353. doi: 10.1007/s00345-016-1826-2. PubMed DOI

Petrelli F, Yasser Hussein MI, Vavassori I, et al. Prognostic factors of overall survival in upper urinary tract carcinoma: a systematic review and meta-analysis. Urology. 2017;100:9–15. doi: 10.1016/j.urology.2016.07.036. PubMed DOI

Fojecki G, Magnusson A, Traxer O, et al. Consultation on UTUC, Stockholm 2018 aspects of diagnosis of upper tract urothelial carcinoma. World J Urol. 2019;37(11):2271–2278. doi: 10.1007/s00345-019-02732-8. PubMed DOI PMC

Mostofi FK, Sobin LH, Torloni H et al (1973) Histological typing of urinary bladder tumours. World Health Organization. https://apps.who.int/iris/handle/10665/41533. Accessed Nov 4 2020

Compérat EM, Burger M, Gontero P, et al. Grading of urothelial carcinoma and the new “World Health Organisation classification of tumours of the urinary system and male genital organs 2016”. Eur Urol Focus. 2019;5(3):457–466. doi: 10.1016/j.euf.2018.01.003. PubMed DOI

Humphrey PA, Moch H, Cubilla AL, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs—part B: prostate and bladder tumours. Eur Urol. 2016;70(1):106–119. doi: 10.1016/j.eururo.2016.02.028. PubMed DOI

Miyamoto H, Miller JS, Fajardo DA, et al. Non-invasive papillary urothelial neoplasms: the 2004 WHO/ISUP classification system. Pathol Int. 2010;60(1):1–8. doi: 10.1111/j.1440-1827.2009.02477.x. PubMed DOI

Chen Z, Ding W, Xu K, et al. The 1973 WHO classification is more suitable than the 2004 WHO classification for predicting prognosis in non-muscle-invasive bladder cancer. PLoS ONE. 2012;7(10):e47199. doi: 10.1371/journal.pone.0047199. PubMed DOI PMC

SEER Incidence Database—SEER Data & Software. SEER. https://seer.cancer.gov/data/index.html. Accessed 8 Oct 2020

Rink M, Fajkovic H, Cha EK, et al. Death certificates are valid for the determination of cause of death in patients with upper and lower tract urothelial carcinoma. Eur Urol. 2012;61(4):854–855. doi: 10.1016/j.eururo.2011.12.055. PubMed DOI

Collà Ruvolo C, Nocera L, Stolzenbach LF, et al. Tumor size predicts muscle-invasive and non-organ-confined disease in upper tract urothelial carcinoma at radical nephroureterectomy. Eur Urol Focus. 2021 doi: 10.1016/j.euf.2021.03.003. PubMed DOI

Park J, Ha SH, Min GE, et al. The protective role of renal parenchyma as a barrier to local tumor spread of upper tract transitional cell carcinoma and its impact on patient survival. J Urol. 2009;182(3):894–899. doi: 10.1016/j.juro.2009.05.040. PubMed DOI

Browne BM, Stensland KD, Moynihan MJ, et al. An analysis of staging and treatment trends for upper tract urothelial carcinoma in the national cancer database. Clin Genitourin Cancer. 2018;16(4):e743–e750. doi: 10.1016/j.clgc.2018.01.015. PubMed DOI

Singla N, Fang D, Su X, et al. Preoperative predictors of nonorgan-confined disease in upper-tract urothelial carcinoma differ between China and the United States. Urol Oncol Semin Orig Investig. 2018;36(3):88.e11–88.e18. PubMed

Rouprêt M, Hupertan V, Traxer O, et al. Comparison of open nephroureterectomy and ureteroscopic and percutaneous management of upper urinary tract transitional cell carcinoma. Urology. 2006;67(6):1181–1187. doi: 10.1016/j.urology.2005.12.034. PubMed DOI

Collà Ruvolo C, Würnschimmel C, Wenzel M, et al. Comparison between 1973 and 2004/2016 WHO grading systems in patients with Ta urothelial carcinoma of urinary bladder. J Clin Pathol. 2021 doi: 10.1136/jclinpath-2021-207400. PubMed DOI

Soukup V, Čapoun O, Cohen D, et al. Prognostic performance and reproducibility of the 1973 and 2004/2016 World Health Organization grading classification systems in non-muscle-invasive bladder cancer: a European association of urology non-muscle invasive bladder cancer guidelines panel systematic review. Eur Urol. 2017;72(5):801–813. doi: 10.1016/j.eururo.2017.04.015. PubMed DOI

van Rhijn BWG, van Leenders GJLH, Ooms BCM, et al. The pathologist’s mean grade is constant and individualizes the prognostic value of bladder cancer grading. Eur Urol. 2010;57(6):1052–1057. doi: 10.1016/j.eururo.2009.09.022. PubMed DOI

May M, Brookman-Amissah S, Roigas J, et al. Prognostic accuracy of individual uropathologists in noninvasive urinary bladder carcinoma: a multicentre study comparing the 1973 and 2004 World Health Organisation classifications. Eur Urol. 2010;57(5):850–858. doi: 10.1016/j.eururo.2009.03.052. PubMed DOI

Mariappan P, Fineron P, O’Donnell M, et al. Combining two grading systems: the clinical validity and inter-observer variability of the 1973 and 2004 WHO bladder cancer classification systems assessed in a UK cohort with 15 years of prospective follow-up. World J Urol. 2021;39(2):425–431. doi: 10.1007/s00345-020-03180-5. PubMed DOI PMC

MacLennan GT, Kirkali Z, Cheng L. Histologic grading of noninvasive papillary urothelial neoplasms. Eur Urol. 2007;51(4):889–898. doi: 10.1016/j.eururo.2006.10.037. PubMed DOI

van de Putte EEF, Bosschieter J, van der Kwast TH, et al. The World Health Organization 1973 classification system for grade is an important prognosticator in T1 non-muscle-invasive bladder cancer. BJU Int. 2018;122(6):978–985. doi: 10.1111/bju.14238. PubMed DOI

Guan B, Tang S, Zhan Y, et al. Prognostic performance of the 1973 and 2004 WHO grading classification in upper tract urothelial carcinoma. Urol Oncol Semin Orig Investig. 2019;37(8):529.e19–529.e25. PubMed

Biological and prognostic implications of biopsy upgrading for high-grade upper tract urothelial carcinoma at nephroureterectomy