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Purpose: There is a paucity of long-term objective and patient-reported outcomes after definitive perineal urethrostomy for complex urethral strictures. Our objective is to determine comprehensive long-term success of perineal urethrostomy with our 15-year experience at a reconstructive referral center., Materials and Methods: Patients who underwent perineal urethrostomy between 2009 and 2023 were identified. A comprehensive long-term follow-up was conducted, evaluating both objective outcomes (retreatment-free survival) and subjective outcomes through the use of validated questionnaires. Additionally, to provide further context for our findings, we conducted a scoping review of all studies reporting outcomes following perineal urethrostomy., Results: Among 76 patients, 55% had iatrogenic strictures, with 82% previously undergoing urethral interventions. At a median follow-up of 55 months, retreatment-free survival was 84%, with 16% of patients experiencing perineal urethrostomy recurrent stenosis. Patient-reported outcomes revealed a generally satisfactory voiding function (Urethral Stricture Surgery Patient-Reported Outcome Measure Lower Urinary Tract Symptoms score) and continence (International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form), with median scores of 4 (range 0-24) and 0 (range 0-21), but with bimodal distributions of sexual function scores (median International Index of Erectile Function-Erectile Function domain: 3.5; median Male Sexual Health Questionnaire-Ejaculation Scale: 21). Treatment satisfaction was very high with a median International Consultation on Incontinence Questionnaire-Satisfaction outcome score of 21 (range 0-24). The scoping review revealed varying success rates ranging from 51% to 95%, highlighting difficulties in comparison due to variable success definitions and patient case mix., Conclusions: Perineal urethrostomy provides effective treatment for complex anterior urethral strictures, with high patient satisfaction, preserved continence function, and favorable voiding outcomes. It presents a viable option for older and comorbid patients, especially after thorough counseling on expected outcomes and potential risks.

Objective: To conduct a population-based study examining cancer-specific mortality (CSM) and other-cause mortality (OCM) differences in patients with radiation-induced secondary bladder cancer (RT-BCa) vs those with primary bladder cancer (pBCa) undergoing radical cystectomy (RC)., Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with T 2-4 N 0-3 M 0 bladder cancer treated with RC, who had previously been treated with external beam radiation therapy (EBRT) or brachytherapy for prostate cancer, as well as patients with T 2-4 N 0-3 M 0 pBCa treated with RC. Cumulative incidence plots and multivariable competing risks regression (CRR) models were used to assess CSM after additional adjustment for OCM. The same methodology was then repeated based on organ-confined (OC: T 2 N 0 M 0 ) and non-organ-confined (NOC: T 3-4 and/or N 1-3 ) disease., Results: Of 9957 RC patients, RT-BCa was identified in 347 (3%) compared with 9610 (97%) who had pBCa. In multivariable CRR models, no CSM differences were recorded in the overall comparison (P = 0.8), nor in sub-groups based on OC and NOC disease (P = 0.8 and 0.7, respectively). Conversely, multivariable CRR models identified RT-BCa as an independent predictor of 1.3-fold higher OCM in the overall cohort and of 1.5-fold higher OCM in those with NOC disease. In a sensitivity analysis of patients with NOC disease, EBRT was associated with higher OCM rates (hazard ratio 1.5). By contrast, OCM rates were not different in those with OC disease (P = 0.8)., Conclusion: Our study showed that RC for RT-BCa was associated with similar CSM rates as RC for pBCa, regardless of disease stage. However, patients who had undergone EBRT exhibited significantly higher OCM in the NOC sub-group., (© 2024 BJU International.)

Background: The Bosniak classification for cystic renal masses has undergone refinements since its inception. The 2019 version provides more objective criteria to enhance interrater agreement but needs validation. This study compares the interrater agreement of the 2005 and 2019 Bosniak classifications for cystic renal masses., Methods: Forty cystic renal masses identified on computed tomography scans were selected, distributed equally among the five classes of the 2005 Bosniak classification. Eight radiology residents participated in 2 consecutive rating sessions using the 2005 and 2019 versions, respectively, with a 1-month wash-out period in between. Interrater reliability was assessed using Fleiss' κ, and changes in cyst classes between the versions were assessed using the Wilcoxon signed-rank test., Results: Fleiss' κ values for interrater reliability were 0.354 (0.286-0.431) for 2005 and 0.373 (0.292-0.487) for 2019, indicating fair to moderate agreement. A significant decrease in cyst grades was noted using the 2019 version (Z = 3.49, r = 0.55, P < 0.001) among all cysts assessed by residents and only in complex cysts assessed by consultants (Z = 1.907, r = 0.275, P = 0.048)., Conclusion: Interrater agreement was similar for both classifications, ranging from fair to moderate. The 2019 version increased the proportion of masses downgraded to lower classes. Comprehensive training may enhance reliability and accuracy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objective: While active surveillance (AS) is an alternative to surgical interventions in patients with small renal masses (SRMs), evidence regarding its oncological efficacy is still debated. We aimed to evaluate oncological outcomes for patients with SRMs who underwent AS in comparison to surgical interventions., Methods: In April 2024, PubMed, Scopus, and Web of Science were queried for comparative studies evaluating AS in patients with SRMs (PROSPERO: CRD42024530299). The primary outcomes were overall (OS) and cancer-specific survival (CSS). A random-effects model was used for quantitative analysis., Key Findings and Limitations: We identified eight eligible studies (three prospective, four retrospective, and one study based on Surveillance, Epidemiology and End Results [SEER] data) involving 4947 patients. Pooling of data with the SEER data set revealed significantly higher OS rates for patients receiving surgical interventions (hazard ratio [HR] 0.73; p = 0.007), especially partial nephrectomy (PN; HR 0.62; p < 0.001). However, in a sensitivity analysis excluding the SEER data set there was no significant difference in OS between AS and surgical interventions overall (HR 0.84; p = 0.3), but the PN subgroup had longer OS than the AS group (HR 0.6; p = 0.002). Only the study based on the SEER data set showed a significant difference in CSS. The main limitations include selection bias in retrospective studies, and classification of interventions in the SEER database study., Conclusions and Clinical Implications: Patients treated with AS had similar OS to those who underwent surgery or ablation, although caution is needed in interpreting the data owing to the potential for selection bias and variability in AS protocols. Our review reinforces the need for personalized shared decision-making to identify patients with SRMs who are most likely to benefit from AS., Patient Summary: For well-selected patients with a small kidney mass suspicious for cancer, active surveillance seems to be a safe alternative to surgery, with similar overall survival. However, the evidence is still limited and more studies are needed to help in identifying the best candidates for active surveillance., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To quantify the differences in 5-year overall survival (OS) between high-grade (Gleason sum 8-10) incidental prostate cancer (IPCa) patients and age-matched male population-based controls, according to treatment type: no active versus active treatment., Materials and Methods: We relied on the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015) to identify not actively treated and actively treated high-grade IPCa patients. For each case, we simulated an age-matched male control (Monte Carlo simulation), relying on Social Security Administration Life Tables (2004-2020) with 5 years of follow-up. Additionally, we relied on Kaplan-Meier plots to display OS for each treatment type. Multivariable Cox regression models were fitted to predict overall mortality (OM)., Results: Of 564 high-grade IPCa patients, 345 (61%) were not actively treated versus 219 (39%) were actively treated, either with radical prostatectomy or radiotherapy. Median OS was 3 years for not actively treated high-grade IPCa patients, with OS difference at 5 years follow-up of 27% relative to their age-matched male population-based controls (37% vs. 64%). Median OS was 8 years for actively treated high-grade IPCa patients, with OS difference at 5 years follow-up of 6% relative to their age-matched male population-based controls (68% vs. 74%). In the multivariable Cox regression model, active treatment independently predicted lower OM (hazard ratio = 0.6; 95% confidence interval = 0.4-0.8; p < 0.001)., Conclusion: Relative to Life Tables' derived age-matched male controls, not actively treated high-grade IPCa patients exhibit drastically worse OS than their actively treated counterparts. These observations may encourage clinicians to consider active treatment in newly diagnosed high-grade IPCa patients., (© 2024 Wiley Periodicals LLC.)

Purpose of Review: Upper tract urothelial carcinoma (UTUC) is a rare malignancy posing significant diagnostic and management challenges. This review provides an overview of the evidence supporting various imaging modalities and offers insights into future innovations in UTUC imaging., Recent Findings: With the growing use of advancements in computed tomography (CT) technologies for both staging and follow-up of UTUC patients, continuous innovations aim to enhance performance and minimize the risk of excessive exposure to ionizing radiation and iodinated contrast medium. In patients unable to undergo CT, magnetic resonance imaging serves as an alternative imaging modality, though its sensitivity is lower than CT. Positron emission tomography, particularly with innovative radiotracers and theranostics, has the potential to significantly advance precision medicine in UTUC. Endoscopic imaging techniques including advanced modalities seem to be promising in improved visualization and diagnostic accuracy, however, evidence remains scarce. Radiomics and radiogenomics present emerging tools for noninvasive tumor characterization and prognosis., Summary: The landscape of imaging for UTUC is rapidly evolving, with significant advancements across various modalities promising improved diagnostic accuracy, patient outcomes, and safety., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Backgrounds: SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity., Methods: Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival., Results: SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis., Conclusions: In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Introduction: Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is guideline-recommended in patients with cT2-T4N0M0 urothelial carcinoma of urinary bladder (UCUB). However, no population-based study validated the survival benefit of NAC recorded in clinical trials in a stage-specific fashion. We addressed this knowledge gap., Methods: Within the Surveillance, Epidemiology, and End Results database (2007-2020), we identified patients with cT2-T4N0M0 UCUB treated with NAC before RC versus RC alone. Cumulative incidence plots and multivariable competing risks regression (CRR) models were fitted. Survival analyses were performed according to organ confined (OC: cT2N0M0) versus nonorgan confined stages (NOC: cT3-T4N0M0)., Results: Of 3,743 assessable patients, 1,020 (27%) underwent NAC versus 2,723 (73%) RC alone. NAC rates increased over time in OC stage (EAPC = 11.9%, P < 0.001) and NOC stage (EAPC = 8.6%, P < 0.001). In OC stage, cumulative incidence plots derived 5-year CSM was 15.6% in NAC and 19.9% in RC alone patients (P = 0.008). In multivariable CRR models, NAC independently predicted lower CSM (hazard ratio (HR): 0.74, P = 0.01). Similarly, in NOC stage, cumulative incidence plots derived 5-year CSM was 36.1% in NAC and 46.0% in RC alone patients (P = 0.01). In multivariable CRR models, NAC independently predicted lower CSM (HR: 0.66, P < 0.001)., Conclusion: NAC is associated with improved CSM compared to RC alone, both in OC and NOC stages. Specifically, the magnitude of the protective NAC effect was greater in NOC than OC patients. Thus, NAC should always be administered in all eligible patients before RC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objective: Although prostate magnetic resonance imaging (MRI) is increasingly used to diagnose and stage prostate cancer (PCa), the biologic and clinical significance of MRI visibility of the disease is unclear. Our aim was to examine the existing knowledge regarding the molecular correlates of MRI visibility of PCa., Methods: The PubMed, Scopus, and Web of Science databases were queried through November 2023. We defined MRI-visible and MRI-invisible lesions based on the Prostate Imaging Reporting and Data System (PI-RADS) score, and compared these based on the genomic, transcriptomic, and proteomic characteristics., Key Findings and Limitations: From 2015 individual records, 25 were selected for qualitative data synthesis. Current evidence supports the polygenic nature of MRI visibility, primarily influenced by genes related to stroma, adhesion, and cellular organization. Several gene signatures related to MRI visibility were associated with oncologic outcomes, which support that tumors appearing as PI-RADS 4-5 lesions harbor lethal disease. Accordingly, MRI-invisible tumors detected by systematic biopsies were, generally, less aggressive and had a more favorable prognosis; however, some MRI-invisible tumors harbored molecular features of biologically aggressive PCa. Among the commercially available prognostic gene panels, only Decipher was strongly associated with MRI visibility., Conclusions and Clinical Implications: High PI-RADS score is associated with biologically and clinically aggressive PCa molecular phenotypes, and could potentially be used as a biomarker. However, MRI-invisible lesions can harbor adverse features, advocating the continued use of systemic biopsies. Further research to refine the integration of imaging data to prognostic assessment is warranted., Patient Summary: Magnetic resonance imaging visibility of prostate cancer is a polygenic trait. Higher Prostate Imaging Reporting and Data System scores are associated with features of biologically and clinically aggressive cancer., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To test the ability of the 2015 modified version of the European Network for the Study of Adrenal Tumors staging system (mENSAT) in predicting cancer-specific mortality (CSM), as well as overall mortality (OM) in adrenocortical carcinoma (ACC) patients of all stages, in a large-scale, and contemporary United States cohort., Methods: We relied on the Surveillance, Epidemiology, and End Results (SEER) database (2004-2020) to test the accuracy and calibration of the mENSAT and subsequently compared it to the 8th edition of the American Joint Committee on Cancer staging system (AJCC)., Results: In 858 ACC patients, mENSAT accuracy was 74.7% for 3-year CSM predictions and 73.8% for 3-year OM predictions. The maximum departures from ideal predictions in mENSAT were +17.2% for CSM and +11.8% for OM. Conversely, AJCC accuracy was 74.5% for 3-year CSM predictions and 73.5% for 3-year OM predictions. The maximum departures from ideal predictions in AJCC were -6.7% for CSM and -7.1% for OM., Conclusion: The accuracy of mENSAT is virtually the same as that of AJCC in predicting CSM (74.7% vs 74.5%) and OM (73.7% vs 73.5%). However, calibration is lower for mENSAT than for AJCC. In consequence, no obvious benefit appears to be associated with the use of mENSAT relative to AJCC in US ACC patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Use of critical care therapies (CCT), that include invasive mechanical ventilation (IMV), total parenteral nutrition (TPN) and other modalities are unknown after radical nephroureterectomy (RNU) for upper urinary tract carcinoma (UUTC). Their relationship with in-hospital mortality is also unknown., Methods: Within the National Inpatient Sample (2008-2019), we identified non-metastatic UUTC patients treated with RNU. Multivariable logistic regression models were used., Results: Of 8,995 patients, 375 (4.2%) received CCT and 82 (0.9%) experienced in-hospital mortality. Of CCT modalities, 215 (2.4%) received IMV and 139 (1.5%) TPN. Temporal CCT, IMV, and TPN trends very closely followed in-hospital mortality trends. Relative to historical UUTC patients (2008-2013), contemporary (2014-2019) patients exhibited lower CCT (Δ = 2.2%, P value < 0.0001), lower IMV (Δ = 1.4%, P < 0.0001), lower TPN (Δ = 2.2%, P < 0.0001), and lower in-hospital mortality (Δ = 0.4%, P = 0.03) rates. Of in-hospital mortalities, 52 out of 82 received CCT but 30 of 82 did not. Median age (> 72 years; odds ratio [OR] 1.4; P = 0.002) and Charlson comorbidity index ≥ 3 (OR 4.1; P < 0.001) and ≥ 1-2 (OR 1.7; P = 0.001) independently predicted overall higher CCT, IMV, TPN, and in-hospital mortality., Conclusion: After RNU, CCT rates parallels in-hospital mortality rates. CCT represents a 5 to 6-fold multiple of in-hospital mortality rate. In RNU patients, CCT rates are higher in older and sicker individuals. Lower CCT rates that are paralleled by lower in-hospital mortality may be interpreted as an indicator of improved quality of care. Ideally all in-hospital mortalities should be predated by CCT exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported .CheckMate 274 is a phase III, randomized, double-blind trial of adjuvant nivolumab versus placebo for muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence after radical resection. The primary end points of disease-free survival (DFS) in intent-to-treat (ITT) and tumor PD-L1 expression ≥1% populations were met. We report results at an extended median follow-up of 36.1 months in the ITT population. In addition, we report interim overall survival (OS) data for the first time and an exploratory analysis among patients with bladder primary tumors (muscle-invasive bladder cancer [MIBC]). Consistent DFS benefit with nivolumab versus placebo was observed in both the ITT (hazard ratio [HR], 0.71 [95% CI, 0.58 to 0.86]) and PD-L1 ≥1% (HR, 0.52 [95% CI, 0.37 to 0.72]) patients. The HR for OS with nivolumab versus placebo was 0.76 (95% CI, 0.61 to 0.96) in the ITT population and 0.56 (95% CI, 0.36 to 0.86) in the PD-L1 ≥1 population. Continuous benefit in nonurothelial tract recurrence-free survival and distant metastasis-free survival was also observed in both patient populations. The exploratory analysis of patients with MIBC also showed continued efficacy benefits, irrespective of PD-L1 status. No new safety signals were reported. Overall, these results further support adjuvant nivolumab as a standard of care for high-risk MIUC after radical resection.

Objective: The aim of this study was to test for the association between paraplegia and perioperative complications as well as in-hospital mortality after radical cystectomy (RC) for non-metastatic bladder cancer., Methods: Perioperative complications and in-hospital mortality were tabulated in RC patients with or without paraplegia in the National Inpatient Sample (2000-2019)., Results: Of 25,527 RC patients, 185 (0.7%) were paraplegic. Paraplegic RC patients were younger (≤70 years of age; 75 vs. 53%), more frequently female (28 vs. 19%), and more frequently harbored Charlson Comorbidity Index ≥3 (56 vs. 18%). Of paraplegic vs. non-paraplegic RC patients, 141 versus 15,112 (76 vs. 60%) experienced overall complications, 38 versus 2794 (21 vs. 11%) pulmonary complications, 36 versus 3525 (19 vs. 14%) genitourinary complications, 33 versus 3087 (18 vs. 12%) intraoperative complications, 21 versus 1035 (11 vs. 4%) infections, and 17 versus 1343 (9 vs. 5%) wound complications, while 62 versus 6267 (34 vs. 25%) received blood transfusions, 47 versus 3044 (25 vs. 12%) received critical care therapy (CCT), and intrahospital mortality was recorded in 13 versus 456 (7.0 vs. 1.8%) patients. In multivariable logistic regression models, paraplegic status independently predicted higher overall CCT use (odds ratio [OR] 2.1, p < 0.001) as well as fourfold higher in-hospital mortality (p < 0.001), higher infection rate (OR 2.5, p < 0.001), higher blood transfusion rate (OR 1.45, p = 0.009), and higher intraoperative (OR 1.56, p = 0.02), wound (OR 1.89, p = 0.01), and pulmonary (OR 1.72, p = 0.004) complication rates., Conclusion: Paraplegic patients contemplating RC should be counseled about fourfold higher risk of in-hospital mortality and higher rates of other untoward effects., (© 2024. The Author(s).)

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a high recurrence rate after surgical therapy with curative intent. Adjuvant radiotherapy (RT) and mitotane therapy have been proposed as options following the adrenalectomy. However, the efficacy of adjuvant RT or mitotane therapy remains controversial. We aimed to evaluate the efficacy of adjuvant therapy in patients who underwent adrenalectomy for localised ACC. The PubMed, Scopus, and Web of Science databases were queried on March 2024 for studies evaluating adjuvant therapies in patients treated with surgery for localized ACC (PROSPERO: CRD42024512849). The endpoints of interest were overall survival (OS) and recurrence-free survival (RFS). Hazard ratios (HR) with 95% confidence intervals (95%CI) were pooled in a random-effects model meta-analysis. One randomized controlled trial (n = 91) and eleven retrospective studies (n = 4,515) were included. Adjuvant mitotane therapy was associated with improved RFS (HR: 0.63, 95%CI: 0.44-0.92, p = 0.016), while adjuvant RT did not reach conventional levels of statistical significance (HR:0.79, 95%CI:0.58-1.06, p = 0.11). Conversely, Adjuvant RT was associated with improved OS (HR:0.69, 95%CI:0.58-0.83, p<0.001), whereas adjuvant mitotane did not (HR: 0.76, 95%CI: 0.57-1.02, p = 0.07). In the subgroup analyses, adjuvant mitotane was associated with better OS (HR:0.46, 95%CI: 0.30-0.69, p < 0.001) and RFS (HR:0.56, 95%CI: 0.32-0.98, p = 0.04) in patients with negative surgical margin. Both adjuvant RT and mitotane were found to be associated with improved oncologic outcomes in patients treated with adrenalectomy for localised ACC. While adjuvant RT significantly improved OS in general population, mitotane appears as an especially promising treatment option in patients with negative surgical margin. These data can support the shared decision-making process, better understanding of the risks, benefits, and effectiveness of these therapies is still needed to guide tailored management of each individual patient., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objective: Trimodal therapy (TMT) provided significant survival advantage relative to external beam radiation therapy (EBRT) alone in prospective trials. However, the magnitude of survival benefit has not been validated in population-based studies. The objective of this study is to determine whether TMT is associated with lower cancer-specific mortality (CSM) rates relative to EBRT., Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with cT2-T4aN0M0 urothelial carcinoma of urinary bladder (UCUB) treated with either TMT or EBRT. Cumulative incidence plots and multivariable competing risk regression (CRR) models addressed CSM after additional adjustment for other-cause mortality and standard covariates. The same methodology was repeated according to stage and age categories., Key Findings and Limitations: Of 4471 patients, 3391 (76%) underwent TMT versus 1080 (24%) EBRT. TMT rates increased over time in the overall cohort (estimated annual percent change [EAPC]: 1.8%, p < 0.001) as well as in organ-confined (OC) stage (EAPC: 1.7%, p < 0.001), but not in non-organ-confined (NOC) stage (p = 0.051). In the overall cohort, 5-yr CSM rates were 43.6% in TMT versus 52.7% in EBRT. In multivariable CRR models, TMT was an independent predictor of lower CSM (hazard ratio [HR]: 0.76, p < 0.001). In OC patients, 5-yr CSM rates were 42.0% in TMT versus 51.9% in EBRT (p < 0.001). In multivariable CRR models, TMT was an independent predictor of lower CSM (HR: 0.74, p < 0.001). Conversely, in NOC patients, TMT did not achieve independent predictor status (p = 0.3)., Conclusions and Clinical Implications: In this population-based study, relative to EBRT, TMT is associated with lower CSM in OC stage, but not in NOC UCUB patients., Patient Summary: In this report, we investigated the survival benefit of administering systemic chemotherapy in addition to radiotherapy in patients who are candidates for bladder-sparing strategies. We found that the combination of systemic chemotherapy and radiotherapy leads to improved cancer-specific survival compared with radiotherapy alone in patients with organ-confined urothelial carcinoma. We conclude that among patients who are candidates for bladder-sparing strategies, following transurethral resection, the combination of radiotherapy and chemotherapy (namely, trimodal therapy) should always be offered in those with organ-confined urothelial carcinoma., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: It is unknown whether 5-year overall survival (OS) differs and to what extent between the American Joint Committee on Cancer stage III non-seminoma testicular germ cell tumor (NS-TGCT) patients and simulated age-matched male population-based controls, according to race/ethnicity groups., Methods: We identified newly diagnosed (2004-2014) stage III NS-TGCT patients within the Surveillance Epidemiology and End Results database 2004-2019. For each case, we simulated an age-matched male control (Monte Carlo simulation), relying on Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS rates between stage III NS-TGCT patients and simulated age-matched male population-based controls, according to race/ethnicity groups (Caucasian, Hispanic, Asian/Pacific Islander and African American). Both, cancer-specific mortality (CSM) and other-cause mortality (OCM) were computed., Results: Of 2054 stage III NS-TGCT patients, 60% were Caucasians versus 33% Hispanics versus 4% Asians/Pacific Islanders versus 3% African Americans. The 5-year OS difference between stage III NS-TGCT patients versus simulated age-matched male population-based controls was highest in Asians/Pacific Islanders (64 vs. 99%, Δ = 35%), followed by African Americans (66 vs. 97%, Δ = 31%), Hispanics (72 vs. 99%, Δ = 27%), and Caucasians (76 vs. 98%, Δ = 22%). The 5-year CSM rate was highest in Asians/Pacific Islanders (32%), followed by African Americans (26%), Hispanics (25%), and Caucasians (20%). The 5-year OCM rate was highest in African Americans (8%), followed by Caucasians (4%), Asians/Pacific Islanders (4%), and Hispanics (2%)., Conclusion: Relative to SSA Life Tables, the highest 5-year OS disadvantage applied to stage III NS-TGCT Asian/Pacific Islander race/ethnicity group, followed by African American, Hispanic and Caucasian, in that order., (© 2024 The Japanese Urological Association.)

Background: The purpose of this study was to test for survival differences according to adjuvant chemotherapy (AC) status in radical nephroureterectomy (RNU) patients with pT2-T4 and/or N1-2 upper tract urothelial carcinoma (UTUC)., Patients and Methods: Within the Surveillance, Epidemiology, and End Results database (SEER, 2007-2020), patients with UTUC treated with AC versus RNU alone were identified. Kaplan-Meier plots and multivariable Cox regression models addressed cancer-specific mortality (CSM)., Results: Of 1995 patients with UTUC, 804 (40%) underwent AC versus 1191 (60%) RNU alone. AC rates increased from 36.1 to 57.0% over time in the overall cohort [estimated annual percentage changes (EAPC) ± 4.5%, p < 0.001]. The increase was from 28.8 to 50.0% in TanyN0 patients (EAPC ± 7.8%, p < 0.001) versus 50.0-70.9% in TanyN1-2 patients (EAPC ± 2.3%, p = 0.002). Within 698 patients harboring TanyN1-2 stage, median CSM was 31 months after AC versus 16 months in RNU alone (Δ = 15 months, p < 0.0001) and AC independently predicted lower CSM [hazard ratio (HR) 0.64; p < 0.001]. Similarly, within subgroup analyses according to stage, relative to RNU alone, AC independently predicted lower CSM in T2N1-2 (HR 0.49; p = 0.04), in T3N1-2 (HR 0.72; p = 0.015), and in T4N1-2 (HR 0.49, p < 0.001) patients. Conversely, in all TanyN0 as well as in all stage-specific subgroup analyses addressing N0 patients, AC did not affect CSM rates (all p > 0.05)., Conclusions: In RNU patients, AC use is associated with significantly lower CSM in lymph-node-positive (N1-2) patients but not in lymph-node-negative patients (N0). The distinction between N1-2 and N0 regarding the effect of AC on CSM applied across all T stages from T2 to T4, inclusively., (© 2024. Society of Surgical Oncology.)

In this review, we revisit the pivotal role of fibroblast growth factor receptor 3 (FGFR3) in bladder cancer (BLCA), underscoring its prevalence in both non-muscle-invasive and muscle-invasive forms of the disease. FGFR3 mutations in up to half of BLCAs play a well-established role in tumorigenesis, shaping distinct tumor initiation patterns and impacting the tumor microenvironment (TME). Emphasizing the importance of considering epithelial-mesenchymal transition profile and TME status, we revisit their relevance in predicting responses to immune checkpoint inhibitors in FGFR3-mutated BLCAs. This writing highlights the initially promising yet transient efficacy of the FGFR inhibitor Erdafitinib on FGFR3-mutated BLCA, stressing the pressing need to unravel resistance mechanisms and identify co-targets for future combinatorial studies. A thorough analysis of recent preclinical and clinical evidence reveals resistance mechanisms, including secondary mutations, epigenetic alterations in pathway effectors, phenotypic heterogeneity, and population-specific variations within FGFR3 mutational status. Lastly, we discuss the potential of combinatorial treatments and concepts like synthetic lethality for discovering more effective targeted therapies against FGFR3-mutated BLCA., (© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of Sun Yat‐sen University Cancer Center.)

Objective: To address cancer-specific mortality free-survival (CSM-FS) differences in patients with urothelial carcinoma of the urinary bladder (UCUB) vs non-UCUB who underwent trimodal therapy (TMT), according to organ confined (OC: T2N0M0) vs non-organ confined (NOC: T3-4NanyM0 or TanyN1-3M0) clinical stages., Patients and Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with cT2-T4N0-N3M0 bladder cancer treated with TMT, defined as the combination of transurethral resection of bladder tumour, chemotherapy, and radiotherapy. Temporal trends described TMT use over time. Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM in UCUB vs non-UCUB according to OC vs NOC stages., Results: Of 5130 assessable TMT-treated patients, 425 (8%) harboured non-UCUB vs 4705 (92%) who had UCUB. The TMT rates increased for patients with OC UCUB from 92.4% to 96.8% (estimated annual percentage change of 0.4%, P < 0.001), but not in the NOC stages (P = 0.3). In the OC stage, the median CSM-FS was 36 months in patients with non-UCUB vs 60 months in those with UCUB, respectively (P = 0.01). Conversely, in the NOC stage, the median CSM-FS was 23 months both in UCUB and non-UCUB (P = 0.9). In the MCR models addressing OC stage, non-UCUB histology independently predicted higher CSM (hazard ratio 1.45, P = 0.004), but not in the NOC stage (P = 0.9)., Conclusion: In OC UCUB, TMT rates have increased over time in a guideline-consistent fashion. Patients with OC non-UCUB treated with TMT showed a CSM disadvantage relative to OC UCUB. In the NOC stage, use of TMT resulted in dismal CSM, regardless of UCUB vs non-UCUB histology., (© 2024 BJU International.)

Background and Objective: Growing evidence supports the use of neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). However, the implications of residual UTUC at radical nephroureterectomy (RNU) after NAC are not well characterized. Our objective was to compare oncologic outcomes for pathologic risk-matched patients who underwent RNU for UTUC who either received NAC or were chemotherapy-naïve., Methods: We retrospectively identified 1993 patients (including 112 NAC recipients) who underwent RNU for nonmetastatic, high-grade UTUC between 1985 and 2022 in a large, international, multicenter cohort. We divided the cohort into low-risk and high-risk groups defined according to pathologic findings of muscle invasion and lymph node involvement at RNU. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) estimates were calculated using the Kaplan-Meier method. Multivariable analyses were performed to determine clinical and demographic factors associated with these outcomes., Key Findings and Limitations: Among patients with low-risk pathology at RNU, RFS, OS, and CSS were similar between the NAC and chemotherapy-naïve groups. Among patients with high-risk pathology at RNU, the NAC group had poorer RFS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 2.10-4.48), OS (HR 2.06, 95% CI 1.33-3.20), and CSS (subdistribution HR 2.54, 95% CI 1.37-4.69) in comparison to the pathologic risk-matched, chemotherapy-naïve group. Limitations include the lack of centralized pathologic review., Conclusions and Clinical Implications: Patients with residual invasive disease at RNU after NAC represent a uniquely high-risk population with respect to oncologic outcomes. There is a critical need to determine an optimal adjuvant approach for these patients., Patient Summary: We studied a large, international group of patients with cancer of the upper urinary tract who underwent surgery either with or without receiving chemotherapy beforehand. We identified a high-risk subgroup of patients with residual aggressive cancer after chemotherapy and surgery who should be prioritized for clinical trials and drug development., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the value of flexible blue-light cystoscopy (BLC) vs flexible white-light cystoscopy (WLC) in the surveillance setting of non-muscle-invasive bladder cancer (NMIBC)., Methods: All major databases were searched for articles published before May 2023 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was the accuracy of flexible BLC vs WLC in detecting bladder cancer recurrence among suspicious bladder lesions., Results: A total of 10 articles, comprising 1634 patients, were deemed eligible for the quantitative synthesis. In the meta-analysis focusing on the detection of disease recurrence, there was no difference between flexible BLC and WLC (odds ratio [OR] 1.08, 95% confidence interval [CI] 0.82-1.41)]; the risk difference (RD) showed 1% of flexible BLC, corresponding to a number needed to treat (NNT) of 100. In the subgroup meta-analysis of detection of carcinoma in situ (CIS) only, there was again no significant difference between flexible BLC and WLC (OR 1.19, 95% CI 0.82-1.69), BLC was associated with a RD of 2% (NNT = 50). The positive predictive values for flexible BLC and WLC in detecting all types of recurrence were 72% and 66%, respectively, and for CIS they were 39% and 29%, respectively., Conclusion: Surveillance of NMIBC with flexible BLC could detect more suspicious lesions and consequently more tumour recurrences compared to flexible WLC, with a increase in the rate of false positives leading to overtreatment. A total of 100 and 50 flexible BLC procedures would need to be performed to find on additional tumor and CIS recurences, respectively. A risk-stratified strategy for patient selection could be considered when using flexible BLC for the surveillance of NMIBC patients., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: To test the association between number as well as locations of organ-specific metastatic sites and overall survival (OS) in systhemic-therapy exposed metastatic urothelial carcinoma of urinary bladder (mUCUB) patients., Methods: Within Surveillance, Epidemiology and End Results database (2010-2020), all systhemic therapy-exposed mUCUB patients were identified. Kaplan-Meier and multivariable Cox regression (CRM) models first addressed OS in patients according to number of metastatic organ-locations: solitary versus 2 versus 3 or more. Subsequently, separate analyses stratified according to location type were completed in patients with solitary metastatic organ-location as well as in patients with 2 metastatic organ-locations., Results: Of 1,310 mUCUB, 1,069 (82%) harbored solitary metastatic organ-location versus 193 (15%) harbored 2 separate metastatic organ-locations versus 48 (3%) harbored 3 or more metastatic organ-locations. Median OS decreased with increasing number of metastatic organ-locations (solitary vs. 2 vs. 3 or more, P < .0001). In multivariable CRM, relative to solitary metastatic organ-location, 2 (HR: 1.57, 95 Confidence interval [CI], 1.33-1.85) as well as 3 or more (HR: 1.69, 95% CI, 1.23-2.31) metastatic organ-locations independently predicted higher overall mortality (OM) (P = .001). In patients with solitary metastatic organ-location, brain metastases independently predicted higher OM (HR 1.67; 95% CI, 1.05-2.67; P = .03) than other locations. In patients with 2 metastatic organ-locations, no differences in OM were recorded according to organ type location., Conclusion: In systemic therapy exposed mUCUB, number of metastatic organ-locations (solitary vs. 2 vs. 3 or more), independently predicted increasingly worse prognosis. In patients with solitary metastatic organ-location, brain purported worse prognosis than others., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Administration of chemotherapy before radical cystectomy (RC) in neoadjuvant setting (NAC) or after RC in adjuvant setting (ADJ) are both associated with a survival benefit relative to RC alone. However, no study directly compared the magnitude of such benefit associated with NAC versus ADJ in locally-advanced UCUB patients (T3-T4N0M0). We addressed this knowledge gap., Methods: Within the Surveillance, Epidemiology, and End Results database (2007-2020), we identified T3-T4N0M0 UCUB patients who underwent NAC+RC or RC+ADJ. Cumulative incidence plots and multivariable competing risks regression (CRR) models were fitted. The same methodology was then re-applied in T3 and then T4 patient subgroups., Results: Of 875 assessable patients, 603 harbored T3 stage (69.0%) and 272 harbored T4 stage (31.0%). Of all 875, 563 (64.0%) underwent RC+ADJ versus 312 (36.0%) NAC+RC. NAC+RC rates increased over time (EAPC=+6.1%, P = .001). Cumulative incidence plots derived five-year CSM rates were 40.3% in NAC+RC versus 36.1% in RC+ADJ patients (P = .2). In multivariable CRR models that also adjusted for OCM, no statistically significant difference in CSM was recorded when NAC+RC was compared to RC+ADJ (HR:0.85, P = .1). Virtually the same observations were made in subgroup analyses where CSM associated with NAC+RC was not different from that recorded in RC+ADJ (HR: 0.89 and P = .4 in T3 stage and HR:0.8 and P = .2 in T4 stage)., Conclusion: In locally-advanced UCUB, NAC rates have sharply increased over time. However, the approach based on neoadjuvant chemotherapy prior to RC have not resulted in a statistically significant CSM benefit relative to RC+ADJ., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: We investigated regional differences in patients with stage III nonseminoma germ cell tumor (NSGCT). Specifically, we investigated differences in baseline patient, tumor characteristics and treatment characteristics, as well as cancer-specific mortality (CSM) across different regions of the United States., Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), patient (age, race/ethnicity), tumor (International Germ Cell Cancer Collaborative Group [IGCCCG] prognostic groups) and treatment (systemic therapy and retroperitoneal lymph dissection [RPLND] status) characteristics were tabulated for stage III NSGCT patients, according to 12 SEER registries representing different geographic regions. Multinomial regression models and multivariable Cox regression models testing for cancer-specific mortality (CSM) were used., Results: In 3,174 stage III NSGCT patients, registry-specific patient counts ranged from 51 (1.5%) to 1630 (51.3%). Differences across registries existed for age (12%-31% for age 40+), race/ethnicity (5%-73% for others than non-Hispanic whites), IGCCCG prognostic groups (24%-43% vs. 14-24% vs. 3%-20%, in respectively poor vs. intermediate vs. good prognosis), systemic therapy (87%-96%) and RPLND status (12%-35%). After adjustment, clinically meaningful inter-registry differences remained for systemic therapy (84%-97%) and RPLND (11%-32%). Unadjusted 5-year CSM rates ranged from 7.1% to 23.3%. Finally in multivariable analyses addressing CSM, 2 registries exhibited more favorable outcomes than SEER registry of reference (SEER Registry 12): SEER Registry 4 (Hazard Ratio (HR): 0.36) and SEER Registry 9 (HR: 0.64; both P = .004)., Conclusion: We identified important regional differences in patient, tumor and treatment characteristics, as well as CSM which may be indicative of regional differences in quality of care or expertise in stage III NGSCT management., Competing Interests: Disclosures The authors declare that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients., Patients and Methods: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models., Results: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001)., Conclusion: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: Systemic therapy is guideline-recommended for metastatic urothelial carcinoma of the urinary bladder (UCUB). Unmarried status represents an important barrier to treatment access in many primaries. The importance of married status is unknown in the context of systemic therapy in metastatic UCUB and was addressed in the current study., Methods: We relied on the Surveillance, Epidemiology, and End Results database (2004-2020) to identify patients with metastatic UCUB. Univariable and multivariable logistic regression models were fitted to address systemic therapy rates. Additionally, temporal trends were plotted., Results: Overall, 6873 patients with stage IV UCUB were identified. Of those, 4853 (71%) were male. Of males, 2993 (62%) were married vs. 797 (39%) of females. The rates of systemic therapy were 55% in both married males and married females. Married males and females differed from their unmarried counterparts regarding age and race/ethnicity. In males, prior to any adjustment, married status was associated with an odds ratio of 1.46 (P < .001). After adjustment for age and race/ethnicity, the odds ratio increased to 1.73 (P < .001). In females, prior to any adjustment, married status was associated with an odds ratio of 1.94 (P < .001). After adjustment for age and race/ethnicity, the odds ratio decreased to 1.57 (P < .001)., Conclusion: Unmarried males and unmarried females are significantly exposed to lower access to systemic therapy compared to their married counterparts. In consequence, both unmarried men and unmarried women should be given very careful consideration when use of systemic therapy in metastatic UCUB is contemplated., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/objectives: Solitary fibrous tumors (SFTs) represent a rare mesenchymal malignancy that can occur anywhere in the body. Due to the low prevalence of the disease, there is a lack of contemporary data regarding patient demographics and cancer-control outcomes., Methods: Within the SEER database (2000-2019), we identified 1134 patients diagnosed with malignant SFTs. The distributions of patient demographics and tumor characteristics were tabulated. Cumulative incidence plots and competing risks analyses were used to estimate cancer-specific mortality (CSM) after adjustment for other-cause mortality., Results: Of 1134 SFT patients, 87% underwent surgical resection. Most of the tumors were in the chest (28%), central nervous system (22%), head and neck (11%), pelvis (11%), extremities (10%), abdomen (10%) and retroperitoneum (6%), in that order. Stage was distributed as follows: localized (42%) vs. locally advanced (35%) vs. metastatic (13%). In multivariable competing risks models, independent predictors of higher CSM were stage (locally advanced HR: 1.6; metastatic HR: 2.9), non-surgical management (HR: 3.6) and tumor size (9-15.9 cm HR: 1.6; ≥16 cm HR: 1.9)., Conclusions: We validated the importance of stage and surgical resection as independent predictors of CSM in malignant SFTs. Moreover, we provide novel observations regarding the independent importance of tumor size, regardless of the site of origin, stage and/or surgical resection status.