Yasmin Abu-Ghanem

Background and Objectives: Pathological upstaging from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) at radical cystectomy (RC) compromises preoperative risk stratification and may deprive patients of the survival benefit conferred by neoadjuvant chemotherapy. This study aimed to define the frequency and independent predictors of pathological upstaging in a contemporary single-institution cohort, and to characterise its impact on recurrence-free, disease-specific, and overall survival. Materials and Methods: We conducted a retrospective review of a prospectively maintained database of all patients who underwent RC and pelvic lymphadenectomy for urothelial bladder cancer at our institution between January 2009 and December 2023. Upstaging was defined as the final pathological stage ≥ pT2 or pN+ from a clinical stage of p = 0.042), variant histology—predominantly squamous differentiation (p = 0.003)—and urethral involvement (p = 0.003) as independent predictors of upstaging. Upstaged patients had significantly worse 5-year RFS (p < 0.001), DSS (p = 0.01), and OS (p < 0.001) compared with patients who remained NMIBC. No statistically significant difference in survival was observed between patients upstaged at RC and those presenting with primary MIBC. Conclusions: Pathological upstaging occurs in more than a quarter of patients undergoing RC for NMIBC and confers a survival penalty equivalent to that of primary MIBC. Concomitant CIS, variant histology, and urethral involvement identify those at highest risk. These patients warrant aggressive preoperative counselling, expedited surgical planning, and consideration of perioperative systemic therapy.

Introduction: Conservative or upfront radical management for high- and very high-risk non-muscle-invasive bladder cancer continues to be debated, particularly for cases with adverse pathological features. We aimed to compare survival outcomes among NMIBC patients treated with transurethral resection of bladder tumour (TURBT) followed by either Bacillus Calmette–Guérin (BCG), sequential BCG plus electromotive administration of mitomycin C (EMDA-MMC), or upfront radical cystectomy (RC). Materials and Methods: High- and- very high-risk NMIBC cases undergoing TURBT followed by BCG, BCG plus EMDA-MMC, or RC at two international tertiary referral centres between 2009 and 2024 were retrospectively reviewed. Recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier methods. Multivariable Cox regression models were applied to identify factors independently associated with survival outcomes. Results: A total of 1178 patients were included: 852 received BCG, 249 received BCG/EMDA-MMC, and 77 underwent upfront RC. Kaplan–Meier analysis revealed no significant differences in RFS or PFS between the BCG and BCG/EMDA-MMC groups, nor in OS between the three treatment strategies. According to multivariable analysis, concomitant carcinoma in situ (CIS) and increasing T stage at TURBT were independently associated with poorer RFS (HR 1.39; 95% CI 1.05–1.85), PFS (HR 1.95; 95% CI 1.36–2.82), and OS (HR 2.28; 95% CI 1.60–3.25). A second resection conferred a protective effect on PFS (HR 0.72; 95% CI 0.54–0.95). Treatment modality (BCG, BCG/EMDA-MMC, or upfront RC) was not significantly associated with any survival endpoint. Conclusions: In this large multicentre series of patients with high- and very high-risk NMIBC undergoing TURBT, survival outcomes were primarily influenced by clinical–pathological characteristics rather than the adjuvant treatment of choice.

Background: Female patients undergoing radical cystectomy (RC) for bladder cancer have historically presented with more advanced disease and poorer survival outcomes than males. These disparities have been attributed to biological differences, delayed diagnosis, and variations in treatment delivery. Recent data suggest, however, that outcomes may converge when patients are managed in standardized, multidisciplinary, high-volume centers. This study evaluated the influence of gender on perioperative features and oncological outcomes such as disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) at a tertiary uro-oncology center. Methods: We retrospectively reviewed a prospectively maintained database of patients who underwent open or robotic-assisted RC for histologically confirmed urothelial carcinoma between 2014 and 2023 at Guy’s and St. Thomas’ NHS Foundation Trust. Demographic, perioperative, and pathological variables were stratified by gender to assess their association with DFS, DSS, and OS. Results: A total of 887 patients were included: 640 men (72.2%) and 247 women (27.8%), with similar mean age (68.5 vs. 68.1 years) and tumour histology (pure urothelial carcinoma 85% vs. 83%). Men had a higher prevalence of diabetes and chronic kidney disease, but no significant differences were observed in time from referral to surgery (0.93 vs. 1.03 months, p = 0.93), use of neoadjuvant therapy (21.6% vs. 17.3%, p = 0.25), or surgical approach (p = 0.55). Pathological stage distribution was comparable between sexes (pT0–1: 44% vs. 50%; pT2–4: 56% vs. 50%; p = 0.13). Kaplan–Meier analysis revealed no significant gender-related differences in 12-month DFS (77.3% vs. 75.4%, p = 0.20), DSS (85.6% vs. 86.9%, p = 0.56), or OS (81.2% vs. 85.2%, p = 0.70). Conclusion: In this high-volume tertiary center, gender did not independently influence perioperative or survival outcomes following radical cystectomy. These findings suggest that standardized, multidisciplinary management within specialized bladder cancer pathways may mitigate the pathological and survival disparities historically associated with gender.

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.

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.

Objective: Percutaneous nephrolithotomy (PCNL) is the treatment of choice for large renal calculi. The prone position has been considered the preferred position to obtain renal access. However, the supine position has recently gained popularity, which confers several potential advantages. The current study analyses the prognostic factors for successful supine PCNL procedures in a larger tertiary centre. Subjects: Prospective data were collected from all patients undergoing PCNL in the Galdako modified Valdivia position at our institution between February-2007 and September-2020. Surgical outcomes variables collected included: the rate of Endoscopic-combined intra-renal surgery (ECIRS), operative times, surgical effectiveness (no residuals p < 0.001), location (p < 0.001) and Guys-Stone Score (GSS) (p < 0.001) were associated with effectiveness. A Percutaneous nephrostomy tube was sited at the completion of the procedure in 97.3% of patients and a simultaneous double-J stent in 45.3%. Stent insertion was associated with larger stones (p < 0.001), the performance of ECIRS (p < 0.001) and higher GSS (p < 0.001). The overall complication rate was 21.7%. The main type of complication was an infection in 26.2 of the cases followed by the need for repeated nephrostogram in 12.7%. Conclusions: We demonstrate that PCNL in a high-volume centre is safe and efficacious in the Galdalko modified Valdivia position. Patients with smaller stones in the renal pelvis and a low GSS have the highest chance of a successful procedure.

Objective: To review the factors that may influence the ability to achieve the present guidelines’ recommendations in a well-resourced tertiary centre. According to current National Institute for Health and Care Excellence (NICE) guidelines, definitive treatment (primary ureteroscopy (URS) or shock wave lithotripsy (ESWL)) should be offered to patients with symptomatic renal colic that are unlikely to pass the stone within 48 h of diagnosis. Methods: Retrospective review of all patients presenting to the emergency department between January and December 2019 with a ureteric or renal stone diagnosis. The rate of emergency intervention, risk factors for intervention and outcomes were compared between patients who were treated by primary definitive surgery vs. primary symptom relief by urethral stenting alone. Results: A total of 244 patients required surgical management for symptomatic ureteric colic without symptoms of urinary infection. Of those, 92 patients (37.7%) underwent definitive treatment by either primary URS (82 patients) or ESWL (9 patients). The mean time for the procedure was 25.5 h (range: 1–118). Patients who underwent primary definitive treatment were likelier to have smaller and distally located stones than the primary stenting group. Primary ureteroscopy was more likely to be performed in a supervised setting than emergency stenting. Conclusions: Although definitive treatment carries high success rates, in a high-volume tertiary referral centre, it may not be feasible to offer it to all patients, with emergency stenting providing a safe and quick interim measure. Factors determining the ability to provide definitive treatment are stone location, stone size and resident supervision in theatre.

Objectives: To analyze the differences in cost-effectiveness between primary ureteroscopy and ureteric stenting in patients with ureteric calculi in the emergency setting. Patients and Methods: Patients requiring emergency intervention for a ureteric calculus at a tertiary centre were analysed between January and December 2019. The total secondary care cost included the cost of the procedure, inpatient hospital bed days, emergency department (A&E) reattendances, ancillary procedures and any secondary definitive procedure. Results: A total of 244 patients were included. Patients underwent ureteric stenting (62.3%) or primary treatment (37.7%), including primary ureteroscopy (URS) (34%) and shock wave lithotripsy (SWL) (3.6%). The total secondary care cost was more significant in the ureteric stenting group (GBP 4485.42 vs. GBP 3536.83; p = 0.65), though not statistically significant. While mean procedural costs for primary treatment were significantly higher (GBP 2605.27 vs. GBP 1729.00; p < 0.001), costs in addition to the procedure itself were significantly lower (GBP 931.57 vs. GBP 2742.35; p < 0.001) for primary treatment compared to ureteric stenting. Those undergoing ureteric stenting had a significantly higher A&E reattendance rate compared with primary treatment (25.7% vs. 10.9%, p = 0.02) and a significantly greater cost per patient related to revisits to A&E (GBP 61.05 vs. GBP 20.87; p < 0.001). Conclusion: Primary definitive treatment for patients with acute ureteric colic, although associated with higher procedural costs than ureteric stenting, infers a significant reduction in additional expenses, notably related to fewer A&E attendances. This is particularly relevant in the COVID-19 era, where it is crucial to avoid unnecessary attendances to A&E and reduce the backlog of delayed definitive procedures. Primary treatment should be considered concordance with clinical judgement and factors such as patient preference, equipment availability and operator experience.

Objective: To analyse if exposure to sunitinib in the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial, which investigated opposite sequences of cytoreductive nephrectomy (CN) and systemic therapy, is associated with the overall survival (OS) benefit observed in the deferred CN arm. Patients and Methods: A post hoc analysis of SURTIME trial data. Variables analysed included number of patients receiving sunitinib, time from randomisation to start sunitinib, overall response rate by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, and duration of drug exposure and dose in the intention‐to‐treat population of the immediate and deferred arm. Descriptive methods and 95% confidence‐intervals (CI) were used. Results: In the deferred arm, 97.7% (95% CI 89.3–99.6%; n  = 48) received sunitinib vs 80% (95% CI 66.9–88.7%, n  = 40) in the immediate arm. Following immediate CN, 19.6% progressed 4 weeks after CN and the median time to start sunitinib was 39.5 vs 4.5 days in the deferred arm. At week 16, 46.0% had progressed at metastatic sites in the immediate CN arm vs 32.7% in the deferred arm. Sunitinib dose reductions, escalations and interruptions were not statistically significantly different between arms. Among patients who received sunitinib in the immediate or deferred arm the median total sunitinib treatment duration was 172.5 vs 248 days. Reduction of target lesions was more profound in the deferred arm. Conclusions: In comparison to the deferred CN approach, immediate CN impairs administration, onset, and duration of sunitinib. Starting with systemic therapy leads to early and more profound disease control and identification of progression prior to planned CN, which may have contributed to the observed OS benefit.