Cisplatin eligibility in the neoadjuvant setting of patients with muscle-invasive bladder cancer undergoing radical cystectomy.

BACKGROUND: To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFR < 60 mL/minute per 1.73 m2. RESULTS: Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (P = .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (n = 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60 mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59 mL/minute exhibited a measured CrCI ≥ 60 mL/minute. CONCLUSIONS: Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59 mL/minute.

Female non-obstetric urogenital fistula repair: long-term patient-reported outcomes and a scoping literature review.

OBJECTIVE: To investigate long-term and patient-reported outcomes, including sexual function, in women undergoing urogenital fistula (UGF) repair, addressing the lack of such data in Western countries, where fistulas often result from iatrogenic causes. PATIENTS AND METHODS: We conducted a retrospective analysis at a tertiary referral centre (2010-2023), classifying fistulas based on World Health Organisation criteria and evaluating surgical approaches, aetiology, and characteristics. Both objective (fistula closure, reintervention rates) and subjective outcomes (validated questionnaires) were assessed. A scoping review of patient-reported outcome measures in UGF repair was also performed. RESULTS: The study included 50 patients: 17 (34%) underwent transvaginal and 33 (66%) transabdominal surgery. History of hysterectomy was present in 36 patients (72%). The median (interquartile range [IQR]) operating time was 130 (88-148) min. Fistula closure was achieved in 94% of cases at a median (IQR) follow-up of 50 (16-91) months and reached 100% after three redo fistula repairs. Seven patients (14%) underwent reinterventions for stress urinary incontinence after transvaginal repair (autologous fascial slings). Patient-reported outcomes showed median (IQR) scores on the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules (ICIQ-FLUTS) of 5 (3-7) for filling symptoms, 1 (0-2) for voiding symptoms and 4.5 (1-9) for incontinence symptoms. The median (IQR) score on the ICIQ Female Sexual Matters Associated with Lower Urinary Tract Symptoms Module (ICIQ-FLUTSsex) was 3 (1-5). The median (IQR) ICIQ Satisfaction (ICIQ-S) outcome score and overall satisfaction with surgery item score was 22 (18.5-23.5) and 10 (8.5-10), respectively. Higher scores indicate higher symptom burden and treatment satisfaction, respectively. Our scoping review included 1784 women, revealing mixed aetiology and methodological and aetiological heterogeneity, thus complicating cross-study comparisons. CONCLUSIONS: Urogenital fistula repair at a specialised centre leads to excellent outcomes and high satisfaction. Patients with urethrovaginal fistulas are at increased risk of stress urinary incontinence, possibly due to the original trauma site of the fistula.

Urinary function in female patients after traditional, organ-sparing and nerve-sparing radical cystectomy for bladder cancer: a systematic review and pooled analysis.

OBJECTIVES: To determine and summarize the available data on urinary, sexual, and health-related quality-of-life (HRQOL) outcomes after traditional radical cystectomy (RC), reproductive organ-preserving RC (ROPRC) and nerve-sparing RC (NSRC) for bladder cancer (BCa) in female patients. METHODS: The PubMed, SCOPUS and Web of Science databases were searched to identify studies reporting functional outcomes in female patients undergoing RC and urinary diversion for the treatment of BCa. The outcomes of interest were voiding function (for orthotopic neobladder [ONB]), sexual function and HRQOL. The following independent variables were derived and included in the meta-analysis: pooled rate of daytime and nighttime continence/incontinence, and intermittent self-catheterization (ISC) rates. Analyses were performed separately for traditional, organ- and/or nerve-sparing surgical approaches. RESULTS: Fifty-three studies comprising 2740 female patients (1201 traditional RC and 1539 organ-/nerve-sparing RC, and 264 nerve-sparing-alone RC) were eligible for qualitative synthesis; 44 studies comprising 2418 female patients were included in the quantitative synthesis. In women with ONB diversion, the pooled rates of daytime continence after traditional RC, ROPRC and NSRC were 75.2%, 79.3% and 71.2%, respectively. The pooled rate of nighttime continence after traditional RC was 59.5%; this rate increased to 70.7% and 71.7% in women who underwent ROPRC and NSRC, respectively. The pooled rate of ISC after traditional RC with ONB diversion in female patients was 27.6% and decreased to 20.6% and 16.8% in patients undergoing ROPRC and NSRC, respectively. The use of different definitions and questionnaires in the assessment of postoperative sexual and HRQOL outcomes did not allow a systematic comparison. CONCLUSIONS: Female organ- and nerve-sparing surgical approaches during RC seem to result in improved voiding function. There is a significant need for well-designed studies exploring sexual and HRQOL outcomes to establish evidence-based management strategies to support a shared decision-making process tailored towards patient expectations and satisfaction. Understanding expected functional, sexual and quality-of-life outcomes is necessary to allow individualized pre- and postoperative counselling and care delivery in female patients planned to undergo RC.

Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

The optimal number of induction chemotherapy cycles in clinically lymph node-positive bladder cancer.

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.

PD-L1 expression in tumor and inflammatory cells is associated with favorable tumor features and favorable prognosis in muscle-invasive urothelial carcinoma of the bladder not treated by immune checkpoint inhibitors.

BACKGROUND: A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse. METHODS: To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era. RESULTS: Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers. PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p = 0.0255) and was even higher in muscle-invasive (pT2-4) carcinomas (29.3%; p < 0.0001). However, within pT2-4 carcinomas, PD-L1 positivity was linked to low pT stage (p = 0.0028), pN0 (p < 0.0001), L0 status (p = 0.0005), and a better prognosis within 512 patients with cystectomy who never received CPIs (p = 0.0073 for tumor cells and p = 0.0086 for inflammatory cells). PD-L1 staining in inflammatory cells was significantly linked to PD-L1 staining in tumor cells (p < 0.0001) and both were linked to a positive p53 immunostaining (p < 0.0001). CONCLUSION: It cannot be fully excluded that the strong statistical link between PD-L1 status and favorable histological tumor features as well as better prognosis could influence the outcome of studies evaluating CPIs in muscle-invasive urothelial carcinoma.

Advancing Intraoperative Assessment of Urethral Stricture Anatomic Variation: A Prospective Proof-of-Concept Study.

INTRODUCTION: Urethral strictures, particularly those refractory to endoscopic interventions, are commonly treated through open urethroplasty. However, predicting recurrence in homogeneous patient populations remains challenging. METHODS: To address this, we developed an intraoperative urethral stricture assessment tool aiming to identify comprehensive risk predictors. The assessment includes detailed parameters on stricture location, length, urethral bed width, spongiosum thickness, obliteration grade, and spongiofibrosis extension. The tool was prospectively implemented in 106 men with anterior one-stage augmentation urethroplasty from April 2020 to October 2021. RESULTS: An intraoperative granular assessment of intricate stricture characteristics is feasible. Comparative analyses revealed significant differences between bulbar and penile strictures. Bulbar strictures exhibited wider urethral beds and thicker spongiosum compared to penile strictures (all p < 0.001). The assessment showed marked variations in the degree of obliteration and spongiofibrosis extension. CONCLUSION: Our tool aligns with efforts to standardize urethral surgery, providing insights into subtle disease intricacies and enabling comparisons between institutions. Notably, intraoperative assessment may surpass the limitations of preoperative imaging, emphasizing the necessity of intraoperative evaluation. While limitations include a single-institution study and limited sample size, future research aims to refine this tool and determine its impact on treatment strategies, potentially improving long-term outcomes for urethral strictures.

Mucomucosal anastomotic non-transecting augmentation (MANTA) urethroplasty: a ventral modification for obliterative strictures.

OBJECTIVES: To present a surgical modification for the repair of bulbar urethral strictures containing short, highly obliterative segments and report on long-term objective and patient-reported outcomes. PATIENTS AND METHODS: We considered patients undergoing bulbar buccal mucosal graft urethroplasty (BMGU) between July 2016 and December 2019. Eligibility criteria for mucomucosal anastomotic non-transecting augmentation (MANTA) urethroplasty were strictures of ≥2 cm with an obliterative segment of ≤1.5 cm. The stricture is approached ventrally to avoid extensive dissection and mobilisation. Dorsally, the scar is superficially excised and the spongiosum is left intact. Dorsal mucomucosal anastomosis is complemented by ventral onlay graft. Perioperative characteristics were prospectively collected including uroflowmetry data and validated patient-reported outcome measures on voiding, erectile, and continence function. We evaluated functional follow-up, incorporating patient-reported (lower urinary tract symptoms [LUTS] score) and functional success. Recurrence was defined as need of re-treatment. RESULTS: Of 641 men treated with anterior BMGU, 54 (8.4%) underwent MANTA urethroplasty. Overall, 26 (48%) and 45 (83%) had a history of dilatation and urethrotomy, respectively, and 14 (26%) were redo cases. Location was bulbar in 38 (70%) and penobulbar in 16 patients (30%), and the mean (SD) graft length was 4.5 (1.4) cm. At a median (interquartile range) follow-up of 41 (27-53) months, the functional success rate was 93%. Whereas the median LUTS score significantly improved from baseline to postoperatively (13 vs 3.5; P < 0.001), there was no change in erectile function (median International Index of Erectile Function - erectile function domain score 27 vs 24) or urinary continence (median International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form sum score 0 vs 0; all P ≥ 0.4). All patients were 'satisfied' (27%) or 'very satisfied' (73%) with the outcome of their operation. CONCLUSION: With excellent long-term objective and patient-reported outcomes, MANTA urethroplasty adds to the armamentarium for long bulbar strictures with a short obliterative segment.

Oncological validation and discriminative ability of pentafecta criteria after open radical cystectomy.

OBJECTIVES: To validate the pentafecta criteria (PC) proposed by the PROMETRICS group for outcome reporting after radical cystectomy in an open radical cystectomy (ORC) cohort with long-term follow-up and to assess the discriminative ability of PC attainment for oncological endpoints. PATIENTS AND METHODS: Between January 2009 and December 2017, 420 patients underwent ORC with pelvic lymph node dissection and urinary diversion for non-metastatic bladder cancer. The PC were defined as reported by the PROMETRICS group. The primary endpoint was PC attainment, and oncological outcomes comprised further endpoints. We used uni- and multivariable logistic regression analysis to assess predictors of PC attainment. The discriminative ability of PC for overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM) was compared using Kaplan-Meier curves and cumulative incidence functions. After stratification by the number of PC attained, the association between PC attainment and the survival endpoints was tested on multivariable Cox regression and competing-risks models. RESULTS: A total of 108 patients (26%) fulfilled all PC, while 195 (46%), 77 (18%), 35 (8.3%) and five (1.2%) attained 4/5, 3/5, 2/5 and ≤1/5 PC, respectively. Increasing age-adjusted Charlson comorbidity index (odds ratio [OR] 0.80, P = 0.015) and incontinent diversion (OR 0.38, P = 0.005) were independent predictors of PC non-attainment. The median follow-up was 73 months. PC attainment (≥4/5 vs 3/5 vs ≤2/5 PC attained) was used to stratify patients into groups at significantly different risk of death (P < 0.001). A decreasing number of PC attained (<4/5) was associated with unfavourable survival estimates for both OM and CSM (all P ≤ 0.005) but not for OCM (all P ≥ 0.2). CONCLUSIONS: The PC proposed by the PROMETRICS group represent accurate quality indicators for oncological outcome reporting after ORC for non-metastatic bladder cancer and have a distinct discriminative ability to predict long-term OM and CSM.

(De-)centralized health care delivery, surgical outcome, and psychosocial health of transgender and gender-diverse people undergoing vaginoplasty: results of a retrospective, single-center study.

PURPOSE: Previous research on genital gender-affirming surgery lacked to build a framework that took various surrounding factors into account. E.g., transgender health care services are delivered in both centralized (by one interdisciplinary institution) and decentralized settings (by different medical institutions spread over several locations). The present study investigated the effects of different structural and clinical aspects of gender-affirming genital surgery on psychosocial outcomes. METHODS: We surveyed former transgender and gender-diverse people who completed a vaginoplasty between 2014 and 2018. 45 participants were included in the study. We calculated hierarchical linear regression analyses to assess the relationship between psychosocial outcome measures (gender congruence, mental health, quality of life) and different aspects of gender-affirming genital surgery (e.g., setting of service delivery). To address shortcomings regarding the small sample size, we applied a rigorous statistical approach (e.g., Bonferroni correction) to ensure that we only identify predictors that are actually related to the outcomes. RESULTS: A non-responder analysis revealed no systematic bias in the recruitment procedure. Treatment satisfaction was a significant predictor for gender congruence. Moreover, we found the setting of service delivery (centralized, decentralized) to predict psychological health and the physical health dimension of quality of life. The effect sizes of our models were moderate to high, and models explained up to 26% of the total variance with a power up to 0.83. CONCLUSION: The present study is an exploratory attempt into the manifold relationships between treatment-related factors (e.g., aesthetic outcome), the setting of service delivery, and their effects on gender-affirming genital surgery.

Outcome of patients with epithelialized cavity formation after excessive vesicourethral anastomotic leak post radical prostatectomy.

PURPOSE: Excessive vesicourethral anastomotic leak (EVAL) is a rare but severe complication after radical prostatectomy (RP). Epithelialized vesicourethral cavity formation (EVCF) usually develops during prolonged catheterization. To our knowledge, there is no description of postoperative outcomes, complications, or functional assessment of these patients who received conservative therapy after EVAL. METHODS: We identified 70 patients (0.56%) with radiographic evidence of EVCF out of 12,434 patients who received RP in 2016-2020 at our tertiary care center. Postoperative radiographic cystograms (CG) were retrospectively re-examined by two urologists individually. We assessed urinary continence (UC), the need for intervention due to anastomotic stricture formation, urinary tract infection (UTI), and symphysitis during the first year of follow-up post-RP. RESULTS: The median age was 66 years [interquartile range (IQR) 61-70 years], the median body mass index was 27.8 kg/m2 (IQR 25.5-30.3 kg/m2), and the median prostate specific antigen before RP was 7.1 ng/ml (IQR 4.7-11.8 ng/ml). The median catheter insertion time was 44.5 days (IQR 35.2-54 days). One-year continence follow-up was available for 27 patients (38.6%), of which 22 (81.5%) reported the use of ≤ one pad, two patients reported the use of two (7.4%) pads/24 h, and three (11.1%) patients reported use > two pads/24 h. Overall, four (5.7%) patients needed surgical reintervention for anastomotic stricture, eight (11.5%) patients presented with symphysitis, and 55 (77.1%) presented with UTI. CONCLUSION: UC in 81.5% 1-year post-RP suggests that conservative treatment in EVAL is a treatment option with an acceptable outcome on UC and should be considered before reintervention for anastomotic insufficiency.

Clinical value of cholinesterase in patients treated with radical nephroureterectomy for upper urinary tract carcinoma.

PURPOSE: To evaluate the prognostic value and the clinical impact of preoperative serum cholinesterase (ChoE) levels on decision-making in patients treated with radical nephroureterectomy (RNU) for clinically non-metastatic upper tract urothelial cancer (UTUC). METHODS: A retrospective review of an established multi-institutional UTUC database was performed. We evaluated preoperative ChoE as a continuous and dichotomized variable using a visual assessment of the functional form of the association of ChoE with cancer-specific survival (CSS). We used univariable and multivariable Cox regression models to establish its association with recurrence-free survival (RFS), CSS, and overall survival (OS). Discrimination was evaluated using Harrell's concordance index. Decision curve analysis (DCA) was used to assess the impact on clinical decision-making of preoperative ChoE. RESULTS: A total of 748 patients were available for analysis. Within a median follow-up of 34 months (IQR 15-64), 191 patients experienced disease recurrence, and 257 died, with 165 dying of UTUC. The optimal ChoE cutoff identified was 5.8 U/l. ChoE as continuous variable was significantly associated with RFS (p < 0.001), OS (p < 0.001), and CSS (p < 0.001) on univariable and multivariable analyses. The concordance index improved by 8%, 4.4%, and 7% for RFS, OS, and CSS, respectively. On DCA, including ChoE did not improve the net benefit of standard prognostic models. CONCLUSION: Despite its independent association with RFS, OS, and CSS, preoperative serum ChoE has no impact on clinical decision-making. In future studies, ChoE should be investigated as part of the tumor microenvironment and assessed as part of predictive and prognostic models, specifically in the setting of immune checkpoint-inhibitor therapy.

Cytokeratin 20 expression is linked to stage progression and to poor prognosis in advanced (pT4) urothelial carcinoma of the bladder.

Cytokeratin 20 (CK20) expression is limited to umbrella cells in the normal urothelium. Since CK20 is often upregulated in neoplastic urothelial cells including dysplasia and carcinoma in situ, immunohistochemical CK20 analysis is often used for the assessment of bladder biopsies. CK20 expression is a feature of luminal bladder cancer subtype, but its prognostic relevance is disputed. In this study, we investigated CK20 on >2700 urothelial bladder carcinomas in a tissue microarray format by immunohistochemistry. Cytoplasmic and membranous CK20 staining was seen in 1319 (51.8%) cancers. The fraction of CK20 positive and especially strongly positive cases increased from pTaG2 low grade (44.5% strongly positive) and pTaG2 high grade (57.7%) to pTaG3 high grade (62.3%; p = 0.0006) but was lower in muscle-invasive (pT2-4) carcinomas (51.1% in all pTa vs. 29.6% in pT2-4; p < 0.0001). Within pT2-4 carcinomas, CK20 positivity was linked to nodal metastasis and lymphatic vessel invasion (p < 0.0001 each) and to venous invasion (p = 0.0177). CK20 staining was unrelated to overall patient survival if all 605 pT2-4 carcinomas were jointly analyzed but subgroup analyses revealed a significant association of CK20 positivity with favorable prognosis in 129 pT4 carcinomas (p = 0.0005). CK20 positivity was strongly linked to the expression of GATA3 (p < 0.0001), another feature of luminal bladder cancer. The combined analysis of both parameters showed best prognosis for luminal A (CK20+/GATA3+, CK20+/GATA3-) and worst outcome for luminal B (CK20-/GATA3+) and basal/squamous (CK20-/GATA3-) in pT4 urothelial carcinomas (p = 0.0005). In summary, the results of our study demonstrate a complex role of CK20 expression in urothelial neoplasms including neoexpression in pTa tumors, a subsequent loss of CK20 expression in a subset of tumors progressing to muscle-invasion, and a stage dependent prognostic role in muscle-invasive cancers.

Altered p53/p16 expression is linked to urothelial carcinoma progression but largely unrelated to prognosis in muscle-invasive tumors.

BACKGROUND: Most inactivating p53 mutations result in a nuclear p53 accumulation - detectable by immunohistochemistry (IHC). p53 alterations leading to a complete lack of p53 protein and absence of immunostaining do also occur - not easily detectable by IHC. p16 is upregulated in p53 inactivated cells. We hypothesized that a positive p16 IHC may help to distinguish p53 inactivation in IHC negative cases. MATERIAL AND METHODS: We investigated p53 and p16 immunostaining on 2710 urothelial bladder carcinomas in a tissue microarray format to understand their impact in relation to clinicopathological parameters of disease progression and patient outcome. RESULTS: p16 immunostaining was absent in normal urothelium but occurred in 63.5% (30.4% strong) of cancers. p16 strongly positive cases increased from pTaG2 low-grade (9.6%) to pTaG3 high-grade tumors (46.5%, p < .0001) but decreased from pTaG3 to pT4 (33.3%; p = .0030). Among pT2-4 carcinomas, p16 positivity was linked to high-grade (p = .0005) but unrelated to overall survival. p53 staining was negative in 8.4%, very weak in 15.4%, weak in 55.3%, strong in 4.7%, and very strong in 16.2% cancers. p53 negative (potentially p53 null phenotype), strong, and very strong p53 positivity increased from pTaG2 low-grade to pTaG3 high-grade tumors (p < .0001) and from pTaG3 to pT2-4 cancers (p = .0007). p53 staining was largely unrelated to histopathological parameters or patient prognosis among pT2-4 carcinomas, except of p53 strong/very strong immunostaining. p16 expression predominated in tumors with very strong, strong, and negative p53 staining and the combination of p53 negative/p16 strongly positive cancers was linked to features of tumor aggressiveness. CONCLUSION: Aberrant p53 and p16 immunostaining increases during grade and stage progression although p53 negative and p16 positive immunostaining lack prognostic significance in pT2-4 carcinomas. Potential diagnostic features are that high level p16 expression is limited to neoplastic urothelium and p53 null phenotype to aggressive cancers (grade 3 and invasive).

Anesthetic Technique (Spinal vs. General Anesthesia) in Holmium Laser Enucleation of the Prostate: Retrospective Analysis of Procedural and Functional Outcomes among 1,159 Patients.

OBJECTIVE: The aim of the study was to compare procedural efficacy, early and late functional outcomes in holmium laser enucleation of the prostate (HoLEP) under spinal anesthesia (SA) versus general anesthesia (GA). METHODS: We retrospectively reviewed patients undergoing HoLEP at our institution between 2012 and 2017. Standard pre-, peri-, and postoperative characteristics were compared according to anesthetic technique. Multivariable logistic regression analyses (MVAs) were employed to study the impact of SA on procedural efficacy and postoperative complications. RESULTS: Our study cohort consisted of 1,159 patients, of whom 374 (32%) underwent HoLEP under SA. While a medical history of any anticoagulation/antiplatelet therapy except low-dose acetylsalicylic acid was significantly more common among patients undergoing GA (16% vs. 10%, p = 0.001), no other significant differences in preoperative characteristics were noted including age, body mass index, American Society of Anesthesiologists Classification (ASA), prostate size, or International Prostate Symptom Score (IPSS), and quality of life scores. Patients under SA exhibited shorter times of enucleation 42 min (interquartile range [IQR]:27-59 vs. 45 min [IQR: 31-68], p = 0.002), and combined time of enucleation/morcellation/coagulation (57 min [IQR: 38-85] vs. 64 min [IQR: 43-93], p = 0.002), as well as fewer complications (Clavien-Dindo ≥3) (12 [3.2%] vs. 55 [7%], p = 0.013). These associations were confirmed in MVA. Patients did not differ significantly with regard to early micturition including post-void residual volume and maximum flow-rate improvement. At a median follow-up of 33 months (IQR: 32-44), patients with SA had a lower IPSS score (median 3 [IQR: 1-6] vs. 4 [IQR: 2-7], p = 0.039). However, no significant differences were observed with respect to any urinary incontinence, urge symptoms, and postoperative pain. CONCLUSION: In this large retrospective series, HoLEP under SA was a safe and efficacious procedure with comparable early and long-term functional outcomes.

Reporting and grading of complications for intracorporeal robot-assisted radical cystectomy: an in-depth short-term morbidity assessment using the novel Comprehensive Complication Index®.

OBJECTIVE: To assess suitability of Comprehensive Complication Index (CCI®) vs. Clavien-Dindo classification (CDC) to capture 30-day morbidity after robot-assisted radical cystectomy (RARC). MATERIALS AND METHODS: A total of 128 patients with bladder cancer (BCa) undergoing intracorporeal RARC with pelvic lymph node dissection between 2015 and 2021 were included in a retrospective bi-institutional study, which adhered to standardized reporting criteria. Thirty-day complications were captured according to a procedure-specific catalog. Each complication was graded by the CDC and the CCI®. Multivariable linear regression (MVA) was used to identify predictors of higher morbidity. RESULTS: 381 complications were identified in 118 patients (92%). 55 (43%), 43 (34%), and 20 (16%) suffered from CDC grade I-II, IIIa, and ≥ IIIb complications, respectively. 16 (13%), 27 (21%), and 2 patients (1.6%) were reoperated, readmitted, and died within 30 days, respectively. 31 patients (24%) were upgraded to most severe complication (CCI® ≥ 33.7) when calculating morbidity burden compared to corresponding CDC grade accounting only for the highest complication. In MVA, only age was a positive estimate (0.44; 95% CI = 0.03-0.86; p = 0.04) for increased cumulative morbidity. CONCLUSION: The CCI® estimates of 30-day morbidity after RARC were substantially higher compared to CDC alone. These measurements are a prerequisite to tailor patient counseling regarding surgical approach, urinary diversion, and comparability of results between institutions.

Oncologic impact of concomitant prostate cancer characteristics at the time of radical cystoprostatectomy for bladder cancer: a population-based analysis.

OBJECTIVE: The aim of this study was to evaluate the prognostic impact of concomitant prostate cancer (PCa) of the cancer-specific mortality (CSM) in the aging patient's papulation with bladder cancer (BCa) treated with radical cystoprostatectomy (RCP). MATERIALS AND METHODS: Within the SEER database (2004-2015), 1468 patients were treated with RCP for BCa harboring histopathological PCa findings. To account for other cause mortality (OCM), multivariable competing risk regression (CRR) tested for potential BCa-CSM differences according to PCa characteristics risk factors predicting CSM. RESULTS: CRR analysis revealed that only following BCa characteristics, as high pathological tumor stages(Ta/Tis/T1 [REF.] vs. T2; HR 2.03, 95% CI: 1.16-3.57, p = 0.014 vs. T3; HR 4.32, 95% CI: 2.45-7.61, p < 0.001 vs. T4; HR 5.06, 95% CI: 2.77-9.22, p < 0.001), as well unfavorable BCa grade IV (Grade I-II [REF.] vs. Grade IV; HR 0.58, 95% CI: 0.35-0.98, p < 0.041) achieved independent predictor status of CSM. With regard to PCa characteristics, none of the covariates yielded independent predictor status of CSM. CONCLUSIONS: Our study, based on the largest population cohort, demonstrates that even in organ-confined BCa patients, concomitant PCa as second malignancy does not represent a risk factor for survival.

Learning benefits of live surgery and semi-live surgery in urology-informing the debate with results from the International Meeting of Reconstructive Urology (IMORU) VIII.

PURPOSE: To analyze the perceived learning opportunities of participants of the International Meeting on Reconstructive Urology (IMORU) VIII for both live surgery demonstrations (LSD) and semi-live surgery demonstrations (SLSD). Safety and educational efficacy of LSD and SLSD at live surgery events (LSE) have been debated extensively, however, objective data comparing learning benefits are missing. METHODS: We conducted a detailed survey, which employed the Kirkpatrick model, a well-established assessment method of training models, to investigate participants preferences as well as the learning benefit of LSE. Furthermore, we employed an audience response system and the Objective Structured Assessment of Technical Skills (OSATS), a well-established assessment method of surgery skills, to let our participants rate the perceived learning opportunity of LSD and SLSD. RESULTS: Of 229 participants at the IMORU VIII, 39.7% returned our questionnaires. 90% stated that they prefer LSD. On all levels of Kirkpatrick's training evaluation model, the IMORU received high ratings, suggesting a high learning benefit. For the assessment of OSATS, a total of 23 surgical cases were evaluable. For all six utilized items, LSD scored significantly better ratings than SLSD. CONCLUSION: Our study suggests that there is still a rationale for LSD, as participants attributed a statistically significant higher learning benefit to LSD over SLDS. Evaluation of the survey showed that for LSE such as the IMORU VIII, a high learning benefit can be expected. Considering that most of our participants are active surgeons with high caseloads, their opinion on the educational value of LSE is of high relevance.

Combined systematic versus stand-alone multiparametric MRI-guided targeted fusion biopsy: nomogram prediction of non-organ-confined prostate cancer.

OBJECTIVE: Based on unfavorable oncological and functional outcomes of non-organ-confined (NOC) prostate cancer (PCa), defined as ≥ pT3, pN1 or both, we aimed to develop a NOC prediction tool based on multiparametric MRI-guided targeted fusion biopsy (TBx). MATERIALS AND METHODS: Analyses were restricted to 594 patients with simultaneous PCa detection at systematic biopsy (SBx), TBx and subsequent radical prostatectomy (RP) at our institution. Development (n = 396; cohort 1) and validation cohorts (n = 198; cohort 2) were used to develop and validate the NOC nomogram. A head-to-head comparison was performed between stand-alone TBx model and combined TBx/SBx model. Second validation was performed in patients with positive TBx, but negative SBx (n = 193; cohort 3). RESULTS: The most parsimonious TBx model included three independent predictors of NOC: pretreatment PSA (OR 1.05 95% CI: 1.01-1.08), highest TBx-detected Gleason pattern (3 + 3 [REF] vs. ≥ 4 + 5; OR 9.3 95% CI 3.8-22) and presence of TBx-detected perineural invasion (OR 2.2 95% CI: 1.3-3.6). The combined TBx/SBx model had the same predictors. For the stand-alone TBx and combined TBx/SBx model, external validation yielded accuracy of 76.5% (95% CI: 69.3-83.1) and 76.6% (95% CI: 69.4-83.6) within cohort 2. The external validation of the stand-alone TBx model yielded 72.4% (95% CI: 65.0-79.6) accuracy within cohort 3. CONCLUSION: Our stand-alone TBx-based nomogram can identify PCa patients at the risk of NOC, using three simple variables, with the similar accuracy as the TBx/SBx-based model. It is non-inferior to combined TBx/SBx-based model and performs with sufficient accuracy in specific patients with positive TBx, but negative SBx.

Exploring the intersection of functional recurrence, patient-reported sexual function, and treatment satisfaction after anterior buccal mucosal graft urethroplasty.

PURPOSE: To evaluate the interplay of stricture recurrence, sexual function, and treatment satisfaction after substitution urethroplasty. METHODS: Observational study of men undergoing 1-stage buccal mucosal graft urethroplasty for anterior urethral stricture between 2009 and 2016. Patients were dichotomized by self-reported treatment satisfaction. Sexual function was assessed by validated and non-validated patient-reported outcome measures. Functional recurrence was defined as symptomatic need of re-intervention. Bivariate analyses, Kaplan-Meier estimates, qualitative and quantitative analyses by uni- and multivariable regression were employed to evaluate the interplay of sexual function, functional recurrence, and treatment satisfaction. RESULTS: Of 534 men with bulbar (82%), penobulbar (11%), and penile strictures (7.3%), 451 (84%) were satisfied with the surgery. There were no differences in stricture location, previous treatment, graft length, or surgical technique between satisfied and unsatisfied patients (all p ≥ 0.2). Recurrence-free survival was 85% at a median follow-up of 33 mo and decreased significantly with each Likert item towards increasing dissatisfaction (p < 0.001). Dissatisfied patients more often reported postoperative loss of rigidity, tumescence, reduced ejaculatory volume, ejaculatory pain, and reduced penile length (all p ≤ 0.042). In 83 dissatisfied men, functional recurrence (28%) and oral morbidity (20%) were the main drivers of dissatisfaction in qualitative analysis. Multivariable analyses revealed functional recurrence and impaired postoperative ejaculatory function as independent predictors of treatment dissatisfaction (all p ≤ 0.029) after adjusting for confounders. CONCLUSION: We found an association of both functional success and sexual function with patient-reported treatment satisfaction after substitution urethroplasty. Such findings validate the clinical significance of defining the symptomatic need for re-intervention as an endpoint and underline the importance of further research evaluating sexual function before and after open urethral reconstruction.