Search Results (330)

Background and Objectives: Radical cystectomy (RC) is standard treatment for muscle-invasive bladder cancer, but the role of gynecologic organ preservation in women remains uncertain. We primarily evaluated the prevalence and predictors of pathological gynecologic organ involvement and secondarily assessed survival and developed a prediction model. Materials and Methods: This multicenter retrospective study included 232 women undergoing RC at 13 tertiary centers. Of the 232 women, 182 had clinical T2 disease and 50 had BCG-unresponsive or very-high-risk Ta/T1 non-muscle-invasive bladder cancer. Overall survival (OS) was the primary endpoint; CSS and RFS were secondary outcomes. Multivariable logistic regression was used to identify predictors and develop preoperative prediction models. Results: Pathological gynecologic organ involvement was identified in 26 patients (11.2%): uterine in 15 (6.5%), vaginal in 11 (4.7%), ovarian in five (2.2%), and adnexal in 21 (9.1%). The median OS was shorter in patients with involvement than in those without (19.0 vs. 48.0 months; p = 0.048). Vaginal and ovarian involvement were associated with shorter OS (both p < 0.001), whereas uterine and adnexal involvement were not. Pathological T stage was associated with organ involvement (p = 0.001), with the highest frequency in pT4 disease. Model 2 showed an AUC of 0.898 and an optimism-corrected AUC of 0.872. A risk score of 0 classified 31.0% as low risk, with an NPV of 97.2% and a sensitivity of 92.3%. Conclusions: Pathological gynecologic organ involvement was uncommon but associated with poorer survival. These findings may support preoperative risk stratification, although the oncologic safety of organ-preserving surgery cannot be established from pathological involvement data alone. Full article

Bacillus Calmette–Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) is a high-risk disease state for which early radical cystectomy remains the guideline-supported oncologic reference in surgically fit patients. Bladder-sparing therapy is necessary for patients ineligible for or declining cystectomy, but it is a preference-sensitive trade-off rather than an equivalent alternative: failure may permit high-grade recurrence, progression, and loss of a curative window. This targeted narrative review synthesizes the evidence for intravesical gemcitabine monotherapy, sequential gemcitabine–docetaxel, and the sustained-release gemcitabine intravesical system TAR-200/INLEXZO, updated through 4 August 2026. Because the review is not systematic and the evidence is dominated by single-arm and retrospective studies, cross-study comparisons are descriptive and establish neither superiority nor equivalence; many gemcitabine studies enrolled mixed BCG-failure cohorts that do not satisfy the contemporary definition. Gemcitabine monotherapy is active but shows declining disease control over time. Sequential gemcitabine–docetaxel has accumulated substantial multicenter observational experience, yet a 2026 retrospective comparison did not demonstrate improved high-grade recurrence-free survival over gemcitabine alone. TAR-200 achieved a centrally confirmed complete response at any time in 82.4% of patients, with a median duration of response of 25.8 months in the single-arm phase 2b SunRISe-1 study and is approved in the United States as INLEXZO for BCG-unresponsive carcinoma in situ with or without papillary tumors; no approved agent holds a papillary-only indication. Comparative patient-reported outcome evidence remains limited, and molecular markers, urinary tumor DNA and transcriptomic subtypes remain investigational rather than validated selection tools. Bladder-sparing treatment should therefore be phenotype- and label-aware, time-limited, and coupled to intensive surveillance with predefined triggers for cystectomy. Full article

Background: Definitions of BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) have become central to therapeutic decision making and clinical trial eligibility. This perspective synthesizes regulatory frameworks with real-world observations to examine how structural conditions shape the applicability of current definitions. These definitions rely on structural prerequisites—adequate BCG exposure, routine maintenance therapy, standardized surveillance, timely access to early radical cystectomy, and complete tumour-level documentation—that are not consistently achievable across diverse health-care environments. This study examines the structural and operational factors that limit the applicability of current BCG-unresponsive criteria in real-world NMIBC care. Methods: A multilevel analysis was performed and integrated four complementary sources of evidence—regulatory frameworks, national claims datasets, multicenter clinical studies, and real-world practice observation—selected for their ability to capture distinct structural dimensions of NMIBC care. Operational assumptions embedded in contemporary definitions were compared with real-world treatment patterns. Structural barriers were categorized across macro-level system constraints, meso-level institutional practices, and micro-level clinical workflows. Results: As a result, a substantial proportion of patients cannot be classified under existing criteria because the exposure-based and time-dependent conditions required by regulatory definitions are not met in routine practice. Maintenance BCG is infrequently delivered, surveillance intervals vary widely, early radical cystectomy is limited by system-level and institutional factors, and key tumour-level variables required for classification are often missing in large-scale datasets. As a result, many patients cannot be reliably classified using existing criteria—not because of tumour biology or clinician behavior, but because the structural assumptions underlying the definitions are unmet. Conclusions: Current BCG-unresponsive criteria rely on structural conditions that are not universally present in real-world NMIBC care. These findings suggest that context-specific operational definitions, together with complementary strategies such as improving guideline implementation, enhancing data completeness, standardizing surveillance practices, and strengthening healthcare infrastructure, may help align regulatory expectations with real-world practice and support equitable access to bladder-sparing therapies. Full article

Radical cystectomy (RC) with urinary diversion (UD) is the standard treatment for muscle-invasive bladder cancer. Although the ileal conduit (IC) is the most commonly performed diversion, its reliance on bowel reconstruction leads to substantial perioperative morbidity and long-term complications. Cutaneous ureterostomy (CU) has re-emerged as an attractive alternative, particularly for elderly and medically frail patients, due to its technical simplicity and avoidance of intestinal manipulation. Recent single-stoma and tubeless modifications have aimed to overcome historical limitations of CU, including stomal stenosis and long-term stent dependence. Compared with IC, modern refinements of single-stoma CU showed shorter operative times and generally shorter hospital stays, largely reflecting avoidance of bowel reconstruction. Estimated blood loss and overall intraoperative complication rates were broadly comparable between diversion types. Contemporary retrospective data on single-stoma modifications showed lower rates of stomal stenosis and improved catheter-free outcomes compared with historical data, while infectious complications and readmission rates remained similar to those of IC in most series. Renal outcomes generally remained stable, with patient factors such as baseline renal function, hydronephrosis, and stent dependence appearing to be more influential for long-term deterioration than diversion type alone. Quality of life after contemporary single-stoma CU was similar to IC, based on the available retrospective evidence. Overall, contemporary single-stoma CU represents a valuable bowel-sparing urinary diversion that may potentially reduce operative burden while maintaining acceptable functional and quality-of-life outcomes. Current retrospective evidence supports its role as a particularly attractive option for elderly and frail patients, although prospective, multicenter comparative studies with standardized outcome reporting are still needed to better define patient selection and long-term outcomes. Full article

Background and Clinical Significance: Anti–myelin-associated glycoprotein (MAG) antibody polyneuropathy is a rare, chronic IgM-mediated demyelinating peripheral neuropathy predominantly affecting sensory nerves in older adults, commonly in association with monoclonal gammopathy of undetermined significance. Reports describing anesthetic management in patients with this condition remain extremely limited, and no specific guidelines currently exist regarding neuromuscular blocking agent (NMBA) use or neuromuscular monitoring in this population. Case Presentation: A 79-year-old man with anti-MAG antibody polyneuropathy (diagnosed in 2007) and IgM monoclonal gammopathy of undetermined significance developed disproportionate progressive lower-extremity weakness and became wheelchair-dependent following COVID-19 infection in 2020. Preoperative evaluation revealed mildly reduced left ventricular function (ejection fraction 49%), mild chronic kidney disease, and marked intrinsic hand muscle atrophy with absent deep tendon reflexes. He was scheduled for robot-assisted radical cystectomy with ileal conduit diversion under combined general and thoracic epidural anesthesia. Before NMBA administration, neuromuscular monitoring was systematically attempted at the ulnar nerve (electromyography and acceleromyography, up to 60 mA/300 μs) and the corrugator supercilii; despite visible muscle contractions following peripheral nerve stimulation, neither modality produced reliable responses at either site. Given the inability to establish reliable monitoring, the administration of NMBAs was considered to carry an unacceptable risk of a prolonged, undetectable blockade. Anesthesia was maintained with deep sevoflurane (2.0–2.5% end-tidal) and remifentanil infusion without NMBAs, titrated to a bispectral index of 40–60. Tracheal intubation was accomplished via video laryngoscopy without NMBA. The 7 h and 30 min surgery was completed without patient movement or surgical compromise. Postoperatively, the patient developed transient upper airway obstruction attributed to glossoptosis, managed successfully with head elevation and nasopharyngeal airway insertion; supplemental oxygen was required until postoperative day 3, and the patient was discharged from the high-dependency unit on postoperative day 5. Conclusions: No measurable quantitative neuromuscular response could be obtained in this patient with advanced anti-MAG antibody neuropathy, despite appropriate application of electromyography- and acceleromyography-based monitoring and the presence of visible muscle contractions following peripheral nerve stimulation. In such circumstances, avoiding NMBA administration in favor of deep volatile or intravenous anesthesia with opioid supplementation may represent a reasonable, hypothesis-generating approach in carefully selected patients; this observation does not establish the general superiority of an NMBA-free strategy, and caution is warranted before generalizing it to procedures such as robotic surgery, in which profound neuromuscular blockade is often considered desirable. Full article

Introduction: The optimal surgical approach for elderly bladder cancer patients remains controversial. We compared perioperative morbidity and short-term outcomes in patients aged ≥ 75 years undergoing open radical cystectomy (ORC) versus robot-assisted radical cystectomy (RARC). Methods: A retrospective, multicenter cohort study was performed including 179 patients aged ≥ 75 years, of whom 101 underwent RARC between 2021 and 2025, and 78 underwent ORC between 2016 and 2020. After 1:1 propensity score matching, 138 patients were analyzed to assess perioperative complications and short-term postoperative outcomes. Pathological outcomes, including pathological stage, tumor grade, lymph node status, and positive surgical margins, were additionally compared between groups. Propensity score matching was performed based on age, body mass index (BMI), pathological stage, comorbidities, prior chemotherapy, and type of urinary diversion. Results: Following propensity score matching, RARC was associated with longer operative time (332 vs. 247 min; p < 0.001) but resulted in significantly lower blood loss (310 vs. 743 mL; p < 0.001), reduced transfusion rates, shorter length of hospital stay (p < 0.001), and fewer overall intraoperative complications (8.7% vs. 18.8%; p = 0.04). Patients undergoing RARC also experienced lower rates of any complications (43.5% vs. 62.3%; p = 0.02) and major complications (Clavien–Dindo III–V: 11.6% vs. 27.5%; p = 0.03). Postoperative mortality was low in both groups and did not differ significantly between RARC and ORC (1.4% vs. 2.9%; p = 1.00). In multivariate analysis, surgical approach independently predicted major complications, with RARC conferring a significantly lower risk (OR 0.75; 95% CI 0.51–0.88; p = 0.04). Analysis of the learning curve showed a significant reduction in major complications over time for RARC (OR 0.68; 95% CI 0.53–0.93; p = 0.01) but not for ORC. Conclusions: RARC offers superior perioperative outcomes, including reduced blood loss, shorter hospitalization, and lower rates of major complications, without differences in short-term pathological outcomes. These data support RARC as a safe and effective option for elderly patients undergoing radical cystectomy. Full article

T1 high-grade (T1HG) urothelial carcinoma of the bladder presents a persistent clinical challenge: despite uniform high-risk classification under EAU guidelines, BCG failure and disease progression rates range from 10% to 40% across published series. Standard clinicopathological variables do not adequately explain this heterogeneity. Three pathological parameters evaluable from routine TURBT specimens—T1 substaging by lamina propria invasion depth, tumour budding at the invasion front, and E-cadherin (CDH1) immunohistochemistry—share a common mechanistic basis in CDH1-driven partial epithelial-to-mesenchymal transition and may refine escalation-oriented risk stratification without requiring additional tissue or molecular testing. We conducted a narrative critical review of PubMed/MEDLINE (January 2000–February 2026; 28 included studies) to evaluate the quantitative evidence for each parameter, with emphasis on reproducibility and BCG-specific outcome data. T1 substaging carries the strongest evidence: pooled progression HR 3.29 (95% CI 2.39–4.51) across 36 studies (n = 6781), with BCG failure of 41% vs. 21% in a centralised BCG-treated registry cohort of 264 patients on multivariable analysis. Tumour budding shows consistent adverse associations in BCG-treated pT1 NMIBC; zero progression was observed in the low-budding subgroup in the only available BCG-specific full-text cohort. CDH1 IHC is directionally supportive but limited by scoring heterogeneity (I² = 63%). All three parameters are mechanistically coherent and assessable from routine TURBT slides. Prospective validation with pre-specified thresholds and standardised scoring protocols is required before clinical implementation can be recommended. Full article

Background/Objectives: Our objective is to evaluate the long-term effects of radical cystectomy and Bricker ileal conduit urinary diversion on upper urinary tract function and structure, with a specific focus on radiological and laboratory changes in renal function. Methods: A retrospective analysis was conducted of 120 patients who underwent radical cystectomy (RC) and Bricker ileal conduit urinary diversion between 2010 and 2024. Clinical, laboratory, and radiological data were assessed over a 24-month follow-up period. Renal parenchymal thickness, kidney volumes, and hydronephrosis grades were analyzed, and the relationship between interventions and renal outcomes was examined. Results: Postoperative follow-up showed a progressive decrease in renal parenchymal thickness and kidney volume, particularly in the left kidney. Hydronephrosis occurred in both renal units, with higher rates on the left side. Despite these changes, only a subset of patients required intervention, typically due to sepsis, acute renal failure, or pain. No significant deterioration in median estimated glomerular filtration rate values was observed; however, patients with interventions showed higher anteroposterior diameter/parenchymal thickness ratios, suggesting increased parenchymal damage. Conclusions: Following radical cystectomy and Bricker ileal conduit diversion, mild to moderate hydronephrosis is not uncommon and does not always necessitate intervention, especially in patients without clinical symptoms. Radiological parameters like renal parenchymal thickness and kidney volume may be valuable for monitoring renal deterioration. Careful follow-up and selective intervention are crucial in preserving renal function in this patient group. Full article

Bladder preservation has emerged as an established treatment option for selected patients with muscle-invasive bladder cancer (MIBC), offering durable oncologic control with the potential to maintain native bladder function and quality of life. Over the past several decades, prospective trials and large institutional experiences have refined trimodality therapy (TMT)—maximal transurethral resection followed by definitive radiation therapy with concurrent radiosensitizing systemic therapy—and clarified principles of patient selection, treatment delivery, surveillance, and salvage. Randomized evidence supports combined-modality therapy as the backbone of bladder preservation, and contemporary comparative analyses suggest outcomes comparable to radical cystectomy in appropriately selected populations. This review synthesizes the clinical foundations of bladder preservation, including radiobiologic considerations, advances in radiation technique, and patterns of recurrence following TMT. We discuss outcomes in higher-risk populations, including locally advanced and node-positive disease, and examine the evolving integration of systemic therapies. The emergence of immune checkpoint inhibitors and antibody–drug conjugates in urothelial carcinoma has reshaped the systemic treatment landscape and raises important questions regarding patient selection, sequencing, and the potential expansion of organ-preserving strategies. Finally, we outline future directions—including response-adaptive approaches, advances in image-guided and adaptive radiotherapy, and ctDNA-enabled risk stratification—while emphasizing the need for prospective validation and multidisciplinary collaboration to refine and optimize bladder-preserving care. Full article

Background/Objectives: Neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC) is a standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC), yet baseline tools to refine prognostic stratification remain limited. We aimed to develop and internally validate a clinicopathological nomogram integrating the neutrophil-to-lymphocyte ratio (NLR) to estimate event-free survival (EFS) in patients with MIBC treated with NAC. Methods: We retrospectively analyzed 210 patients with cT2–T4aN0–1M0 MIBC treated with cisplatin-based NAC at two Spanish institutions between 2010 and 2021. Candidate predictors included demographic, clinicopathological, and routine laboratory variables. A multivariable Cox model with backward selection based on the Akaike information criterion (AIC) was used to derive the final model, and internal validation was performed using 1000 bootstrap resamples. Results: Sex, age, prior non–muscle-invasive bladder cancer (NMIBC), and NLR were retained in the final nomogram. The model showed moderate discrimination, with a Harrell’s c-index of 0.60 and an optimism-corrected c-index of 0.58. The nomogram stratified patients into low-, intermediate-, and high-risk groups, with median EFS not reached, 47.5 months, and 18.0 months, respectively. High-risk patients also showed lower pathological complete response (pCR) rates. Conclusions: This exploratory nomogram integrates an accessible systemic inflammatory marker with baseline clinical variables to identify patients with poorer outcomes despite NAC. External validation in contemporary cohorts is warranted before clinical implementation. Full article

Background. Accurate prediction of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in muscle-invasive urothelial bladder cancer (MIBC) remains an unmet clinical need. The neutrophil-to-platelet/hemoglobin-to-lymphocyte (NPLH) ratio, a composite hematologic index that reflects both systemic inflammation and nutritional oxygen-carrying capacity, has not been previously evaluated as a predictor of NAC response in this setting. Methods. We retrospectively analyzed 114 consecutive patients with MIBC (cT2–T4, N0–N3) who received accelerated MVAC (aMVAC) NAC followed by radical cystectomy at a single academic center. Pretreatment NPLH (calculated as [neutrophils × platelets]/[hemoglobin × lymphocytes]) was assessed as a predictor of pCR (ypT0N0) and tumor regression grade (TRG). Receiver operating characteristic (ROC) curve analysis, Mann–Whitney U test, and logistic regression were used. NPLH performance was compared to NLR and PLR. Results. pCR was achieved in 35 patients (30.7%). Median NPLH was significantly lower in pCR vs. non-pCR patients (33.9 [IQR 23.1–42.4] vs. 47.6 [IQR 30.7–90.4]; p = 0.0007). NPLH yielded an AUC of 0.700 (bootstrap 95% CI 0.596–0.794) for pCR prediction, numerically superior to NLR (AUC 0.645 [0.542–0.741]) and PLR (AUC 0.643 [0.533–0.747]); DeLong test: NPLH vs. NLR p = 0.079, NPLH vs. PLR p = 0.090. At the optimal cut-off of 44.5, NPLH demonstrated 80.0% sensitivity and 57.0% specificity. pCR rates declined progressively across NPLH quartiles: 48.3% (Q1) to 10.3% (Q4). On multivariate logistic regression, log-transformed NPLH was the only independent predictor of pCR (parsimonious model, OR 0.292, 95% CI 0.131–0.652; p = 0.003; EPV = 17.5). A positive correlation was observed between NPLH and TRG score (Spearman r = 0.284; p = 0.0022), with significant differences between TRG 1 and TRG 3 subgroups (p = 0.0036). Conclusions. Pretreatment NPLH is an independent predictor of pCR to aMVAC in MIBC and is numerically superior to NLR and PLR (DeLong p = 0.079). Consisting exclusively of standard complete blood count parameters, NPLH is readily available and inexpensive. This single-center exploratory study is hypothesis-generating and requires prospective external validation before clinical implementation. Full article

Background/Objectives: To evaluate the feasibility, in-hospital mortality, and perioperative morbidity of open radical cystectomy performed entirely under combined spinal-thoracic epidural anesthesia (CSTEA) in patients with a predominantly high anesthetic risk profile. Methods: This retrospective multicenter cohort study included 145 consecutive adults with histologically confirmed bladder cancer who underwent open radical cystectomy with pelvic lymph node dissection and urinary diversion under planned CSTEA at two institutions between 2008 and 2017. The rationale for CSTEA was to preserve spontaneous breathing and avoid planned intubation and neuromuscular blockade in selected patients. The primary endpoint was in-hospital mortality during the index admission. Results: Most patients were classified as American Society of Anesthesiologists (ASA) III (85.5%) or ASA IV (1.4%). Urinary diversion consisted of transureteroureterocutaneostomy in 97 patients (66.9%), ileal conduit in 24 (16.6%), and orthotopic ileal neobladder in 24 (16.6%). No patient required intraoperative conversion to general anesthesia. In-hospital mortality was 0.7% (1/145), and severe complications occurred in 5.5%. Median length of stay was 15 days, and median postoperative pain score was 1. Conclusions: Open radical cystectomy under CSTEA appeared feasible in selected patients and was associated with low in-hospital mortality, low severe complication rates, and favorable early recovery. These findings support CSTEA as a feasibility-based option in experienced centers, while prospective comparative studies using standardized in-hospital, 30-day, and 90-day endpoints are needed. Full article

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 <T2N0M0. Clinicopathological factors were evaluated for their association with upstaging using chi-squared, Fisher’s exact, and logistic regression analyses. Survival outcomes—recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS)—were estimated by the Kaplan–Meier method and compared using the log-rank test. Multivariable Cox proportional hazards regression identified independent prognostic factors. Results: Of 1002 patients who underwent RC during the study period, complete clinicopathological data were available for 826. Primary clinical stage at presentation was MIBC (≥T2) in 448 (54.2%) and NMIBC (<T2) in 378 (45.8%). Among NMIBC patients, 102 (27.0%) were upstaged to MIBC at final pathology. Multivariable logistic regression identified concomitant carcinoma in situ (CIS) (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. Full article

Background/Objectives: Radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is associated with high morbidity. Frailty is an important determinant of surgical outcomes; however, its association with the composite outcome Days Alive and Out of Hospital (DAOH) has not been examined following RC. We assessed the impact of preoperative frailty on 90-day DAOH in older patients undergoing RC for MIBC. Methods: We conducted a retrospective cohort study including 408 consecutive patients aged ≥65 years undergoing RC at a tertiary referral center between 2018 and 2023. Frailty was assessed using the record-based Multidimensional Prognostic Index (r-MPI), classifying patients as non-frail (MPI1), moderately frail (MPI2), or severely frail (MPI3). The primary outcome was 90-day DAOH; secondary outcomes included length of stay (LOS), postoperative complications, delirium, and mortality. DAOH was dichotomized at the cohort median. Associations with low DAOH were analyzed using modified Poisson regression with robust variance estimation. Results: Median 90-day DAOH decreased progressively with increasing frailty: MPI1: 81 days (IQR 76–83), MPI2: 73 days (IQR 62–80), MPI3: 67 days (IQR 52–76); p < 0.01. In multivariable analysis, frailty was independently associated with low DAOH (MPI2: RR 2.46, 95% CI 1.94–3.11; MPI3: RR 3.37, 95% CI 2.55–4.46), whereas age and comorbidity were not. Increasing frailty was consistently linked to worse postoperative outcomes, including longer LOS, higher complication burden and severity, and more frequent delirium. Ninety-day postoperative complication-related mortality increased markedly with frailty (MPI1: 1.6%, MPI2: 11.9%, MPI3: 12.1%; p < 0.01). Conclusions: Preoperative frailty is a strong independent predictor of low 90-day DAOH and adverse postoperative outcomes following RC in older patients. Full article