Contemporary Trends and Predictors Associated with Adverse Pathological Upstaging Among Non-Metastatic Localized Clinical T2 Muscle-Invasive Bladder Cancers Undergoing Radical Cystectomy: Outcomes from a Single Tertiary Centre in the United Kingdom

<b>Introduction</b>: Radical cystectomy (RC) is the gold standard for urothelial cT2-4a, N0, M0 muscle-invasive bladder cancer (MIBC). However, bladder-sparing strategies (BSS) such as Trimodality Therapy (TMT) have emerged as alternative treatments for a select group of localized muscle-confined (cT2) urothelial bladder cancers. Accordingly, reliable preoperative staging and a reliable risk factor assessment linked to pathological upstaging play a key role in adequate counselling and patient selection for BSS. <b>Patients and Methods</b>: cT2 MIBC patients undergoing RC at our institution from 2014 to 2024 were reviewed. Preoperative staging modalities, demographics, and tumour and patient characteristics were assessed. Multivariable logistic regression was applied to explore the relative effect of confounders on any pathological upstaging from robot-assisted or open RC specimens. Subgroup analysis according to the local upstaging (>pT2) or nodal dissemination (pN+) was also performed. <b>Results</b>: <i>N</i> = 275 RCs were included (73.5% males, 26.5% females). Upstaging was documented in <i>n</i> = 141 (51%) cases. Of these, <i>n</i> = 125 (45.5%) were upstaged locally (>pT2) and <i>n</i> = 35 (23%) yielded pN+ disease. Preoperative parameters like gender, the number of TURBTs, previous BCG exposure, and concomitant CIS did not significantly influence the risk of any kind of upstaging (<i>p</i> > 0.05). At multivariable analysis, neoadjuvant chemotherapy (NAC) and multi-disciplinary team (MDT) discussion were found protective (odds ratio [OR]: 0.4, 95%CI 0.2-0.7, <i>p</i> = 0.001 and OR: 0.51, 95%CI 0.2-0.9, <i>p</i> = 0.01). Preoperative FDG-PET assessment yielded higher risk for later pN upstaging (OR: 1.8, 95%CI 1-3, <i>p</i> = 0.05). HG/G3 features at TURBT along with mixed/pure histology variants in RC specimens were the most relevant independent predictors for both any and pT upstaging (OR: 4.3, 95%CI 1-34, <i>p</i> = 0.04 and OR: 2.3, 95%CI 1.1-4.6, <i>p</i> = 0.02 for any upstaging and OR: 5.6, 95%CI 1.3-36, <i>p</i> = 0.02 and OR: 2.5, 95%CI 1.3-5, <i>p</i> = 0.01 for pT upstaging, respectively). <b>Conclusions</b>: In this study, over half of the patients undergoing RC for cT2 were upstaged at the final pathology. Therefore, adequate counselling and examining the non-conventional criteria for prognosis is mandatory in the contemporary era of bladder-preservation strategies.