Mari, Andrea

Objective To validate International Bladder Cancer Group (IBCG) definitions of Bacillus Calmette‐Guérin (BCG)‐unresponsive and BCG‐exposed non‐muscle‐invasive bladder cancer (NMIBC) and assess prognostic heterogeneity across various BCG‐failure types. Patients and Methods From a multicentre international cohort of 3806 BCG‐treated patients, 591 who developed high‐grade NMIBC recurrence following BCG between 2003 and 2024 were included. Progression‐free survival (PFS) was the primary endpoint; cancer‐specific (CSM) and overall mortality (OM) were secondary endpoints. Cumulative incidence functions, competing‐risk models and multivariable Cox regression were used. Results Patients with BCG‐unresponsive and BCG‐exposed disease showed similar PFS, CSM, and OM (all P > 0.05). When stratified into five subgroups, prognosis varied: 5‐year progression rates were 29% for BCG‐unresponsive, 32.5% for late relapse (between 6 and 24 months) after adequate BCG, 30% for BCG‐exposed with inadequate BCG (<24 months from induction), 6.2% for BCG‐resistant, and 14% for very late relapse (>24 months since last BCG) ( P < 0.01). In multivariable analysis, BCG‐exposed after inadequate BCG (subdistribution hazard ratio [sHR] 3.42, 95% confidence interval [CI] 1.33–8.84), late relapse (sHR 3.74, 95% CI 1.59–8.78), and BCG‐unresponsive (sHR 2.34, 95% CI 1.00–5.44) were associated with higher progression risks compared to very late relapse. Limitations include retrospective design and treatment heterogeneity. Conclusions Under IBCG definitions, BCG‐unresponsive and BCG‐exposed NMIBC have similarly poor outcomes. A refined classification reveals prognostic heterogeneity, with late relapses after adequate BCG demonstrating outcomes comparable to BCG‐unresponsive, and very late relapses conferring better prognosis.

Objective To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node‐positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. Patients and Methods We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose‐dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1–3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni‐ and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer‐specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. Results Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles ( P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2‐year OS estimates were 63% (95% confidence interval [CI] 0.53–0.74) and 63% (95% CI 0.58–0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni‐ or multivariable Cox regression analyses. Conclusion Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

Objectives: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). Methods: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990–2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien–Dindo > 3) were assessed between groups. Results: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan–Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22–2.28, p = 0.001 and HR 1.73, 95%CI 1.22–2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta −1.1, 95% CI −2.2–0.02, p = 0.047 and beta −6.1, 95% CI −7.2–5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31–0.79, p = 0.003 and OR 0.27, 95% CI 0.16–0.46, p < 0.001, respectively). Conclusions: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.

Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. Results: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. Conclusions: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed.