Introduction: 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. Patients and Methods: 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. Results: N = 275 RCs were included (73.5% males, 26.5% females). Upstaging was documented in n = 141 (51%) cases. Of these, n = 125 (45.5%) were upstaged locally (>pT2) and n = 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 (p > 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, p = 0.001 and OR: 0.51, 95%CI 0.2–0.9, p = 0.01). Preoperative FDG-PET assessment yielded higher risk for later pN upstaging (OR: 1.8, 95%CI 1–3, p = 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, p = 0.04 and OR: 2.3, 95%CI 1.1–4.6, p = 0.02 for any upstaging and OR: 5.6, 95%CI 1.3–36, p = 0.02 and OR: 2.5, 95%CI 1.3–5, p = 0.01 for pT upstaging, respectively). Conclusions: 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.

Introduction: Absence of residual cancer in radical cystectomy (RC) specimens is a well-known positive prognostic factor for non-muscle and muscle-invasive bladder cancer (NMIBC and MIBC) in patients with or without neoadjuvant chemotherapy (NAC). Understanding the clinical and pathological features associated with a final pT0 status can provide valuable prognostic insights, serve as a surrogate marker for survival outcomes, and help identify candidates suitable for bladder-sparing strategies. Methods: Temporal trends and clinical/demographic characteristics across clinically high-/very-high-risk NMIBC or MIBC RC patients from 2009 to 2024 were explored. Subsequently, RC pT0 patients were propensity score-matched (PSM, 1:1 ratio) with the >pT0 population based on age-adjusted CCI and preoperative clinical stage (cTis-T1 vs. cT2). Multivariable regression modelling was applied to explore predictors of pT0 status stratified according to clinical NMIBC or MIBC status. Results: A total of 655 RCs performed with curative intent were included (43% for MIBC, 57% for NMIBC). Of these, 117 were pT0 at final pathological assessment (68 NMIBC and 49 MIBC). Subsequently, 228 PSM patients (114 pT0 vs. 114 >pT0) were extracted from the original cohort and stratified according to preoperative clinical stage (MIBC vs. NMIBC). In multivariable analysis, male gender was associated with an increased likelihood of pT0 status in the NMIBC cohort (adjusted odds ratio [aOR] 2.89, 95% CI 1.13–7.90). Conversely, BCG failure and concomitant CIS independently reduced the chances of achieving pT0 status (aOR: 0.40, 95% CI 0.19–0.99; aOR: 0.16, 95% CI 0.03–0.97). For MIBC patients, as expected, NAC more than doubled the chances of achieving pT0 status (aOR: 2.20, 95% CI 1.01–6.82). On the other hand, the concomitant presence of CIS reduced the likelihood of pT0 achievement (aOR 0.22, 95% CI, 0.06–0.80). In both cohorts, the presence of variant histology (VH) demonstrated a negative association with pT0 achievement; however, the estimated effect did not reach statistical significance (p = 0.09 and p = 0.08). Conclusions: Our findings suggest potentially raising the threshold for RC consideration in high-risk or very-high-risk NMIBC patients with a favourable risk profile. MIBC patients without additional risk factors (CIS and VH) are more likely to achieve a tumour-free status, particularly when adequately receiving NAC.

Introduction: The role of urethrectomy at the time of Robotic-Assisted or Open Radical Cystectomy (RARC, ORC) is controversial. Whether urethrectomy should be performed at the time of RARC/ORC or delayed up to a 3–6 month interval is unclear. We performed a retrospective cohort analysis of perioperative and survival outcomes in patients with high-risk NMIBCs or non-metastatic MIBCs at our institution who underwent either concomitant or deferred urethrectomy after RC. Materials and Methods: cTis-T1 or cT2-T4, N0-1, M0 BC patients who underwent RARC or ORC from 2009 to 2024 were reviewed. Clinical, demographic, tumour, and patient characteristics and perioperative variables were assessed across concomitant and delayed urethrectomy groups. Multivariate logistic analysis was performed to estimate the impact of significant variables on intraoperative and postoperative outcomes. Univariable Kaplan–Meier and multivariable Cox regression modelling was implemented to explore the relative effect of time of urethrectomy on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: A total of n = 58 patients (n = 47 delayed vs. n = 11 concomitant) with similar demographic characteristics were included. The concomitant urethrectomy group experienced longer operative time and greater blood loss (379 ± 65 min and 430 ± 101 mL vs. 342 ± 82 min and 422 ± 125 mL, with p = 0.049 and p = 0.028, respectively). Hospital readmission rates were higher in the concomitant urethrectomy group (36.4% vs. 8.5%, p = 0.016; OR: 17.9; 95% CI 1.2–265; p = 0.036). In Cox regression analysis, the timing of urethrectomy had no influence on PFS, CSS, or OS (all p > 0.05). Conclusions: Our study suggests that urethrectomy can be safely deferred unless urothelial disease is clearly present pre- or intraoperatively without compromising survival outcome and with the advantage of reducing surgical morbidity at the time of RC.