{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:15:15Z","timestamp":1792077315619,"version":"4.4.0"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To compare the predictive performance of the World Health Organization (WHO) 1973, WHO 2004\/2022, the three\u2010tier (low grade [LG]\/Grade 1 [G1]\u2013G2, high grade [HG]\/G2, and HG\/G3), and four\u2010tier (LG\/G1, LG\/G2, HG\/G2, and HG\/G3) hybrid grading systems in Ta non\u2010muscle\u2010invasive bladder cancer (NMIBC), by evaluating recurrence\u2010free survival (RFS) and progression\u2010free survival (PFS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>This retrospective multicentre study included 1233 patients with pTa NMIBC treated with transurethral resection of bladder tumour, eventually followed by intravesical instillations as determined by their physicians, between 2010 and 2023, across 18 Italian hospitals. Pathologists graded resected tissues using the WHO 1973, WHO 2004\/2022 classifications, and hybrid three\u2010tier (LG, HG\/G2, HG\/G3) and four\u2010tier (LG\/G1, LG\/G2, HG\/G2, HG\/G3) systems. Kaplan\u2013Meier curves estimated RFS and PFS. Discriminative performance was assessed using Harrell's concordance index (C\u2010index).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 1233 patients with pTa NMIBC, 890 were classified as LG and 343 as HG according to the WHO 2004\/2022 grading system, while 586, 405, and 242 were categorised as G1, G2, and G3, respectively, under the WHO 1973 system. With a median (interquartile range) follow\u2010up of 26\u2009(14\u201348)\u2009months, 418 patients experienced recurrence, including 184 with HG recurrence and 42 who progressed to MIBC. The C\u2010index values for RFS were 0.60, 0.56, 0.57, and 0.61 for the WHO 1973, WHO 2004\/2022, hybrid three\u2010tier, and four\u2010tier grading systems, respectively. For progression, the C\u2010index values were 0.80, 0.74, 0.75, and 0.81 across the same systems, underscoring the superior predictive capacity of the four\u2010tier classification. Nonetheless, the low number of MIBC progression events limits the robustness of these analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings highlight the superior prognostic accuracy of the four\u2010tier hybrid classification in predicting recurrence and progression in patients with stage Ta NMIBC. By combining strengths from the WHO 1973 and 2004\/2022, this hybrid model shows promise as tool for enhancing NMIBC patient management in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bju.16828","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T05:29:11Z","timestamp":1750829351000},"page":"882-890","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Enhanced prognostic value of four\u2010tier hybrid grading system in Ta non\u2010muscle\u2010invasive bladder cancer"],"prefix":"10.1111","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9250-7858","authenticated-orcid":false,"given":"Matteo","family":"Ferro","sequence":"first","affiliation":[{"name":"Unit of Urology, Department of Health Science, ASST Santi Paolo and Carlo University of Milan  Milan 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