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Objective: To analyze clinical and radiological features and trends in the management pattern of renal angiomyolipomas (AML) in a tertiary care center over a 30-year period., Patients and Methods: We retrospectively reviewed the charts of patients referred to our institutions from 1992 to 2022 with final diagnosis of AML. Demographics, clinical presentation, radiological findings, renal function status, and treatment options were recorded. Clinical presentation and management trends were described over the study period. Moreover, impact of tumor size on presentation and management was studied by considering 4cm as cut-off point., Results: Overall, three hundred and ninety-two patients (mean age 61.7±16.9years) were included in the analysis. An incidental diagnosis occurred in 75.2% of cases. Of all, 277 (70.5%) and 115 (29.5%) patients were respectively managed with active treatment and surveillance. Partial nephrectomy represented the first elected surgical approach (49%). Presenting tumor size continuously decreased over the study period (P<0.001). Treatment options have shifted, with significant trending towards less invasive approaches such as angio-embolization or active surveillance. Overtreatment remains an issue., Conclusion: In the current era AMLs are smaller and more likely to be diagnosed readily because of the widespread utilization of different imaging modalities. Despite a significant shift in the management toward active surveillance, overtreatment is still overused., Competing Interests: Disclosure of interest The authors declare that they have no competing interest., (Copyright © 2025 Elsevier Masson SAS. All rights reserved.)

Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies. This includes 3 phase I studies evaluating the safety and initial tumor activity of TAR-200 and 5 phase II/III studies assessing the efficacy and safety of TAR-200, with or without systemic cetrelimab, as a treatment option for patients with HR NMIBC (bacillus Calmette-Guérin naive [papillary and carcinoma in situ] and MIBC (neoadjuvant and patients ineligible for or refusing radical cystectomy). Pharmacokinetics demonstrate intravesical gemcitabine delivery via TAR-200 over a prolonged period without detectable plasma levels. Phase I studies showed that TAR-200 is well tolerated, with preliminary antitumor activity in intermediate-risk NMIBC and MIBC. Preliminary data from the phase IIb SunRISe-1 study demonstrate that TAR-200 monotherapy is safe and effective in patients with bacillus Calmette-Guérin-unresponsive high-risk NMIBC. TAR-200 represents an innovative approach to the local treatment of bladder cancer., Competing Interests: Declaration of competing interest Siamak Daneshmand has received grants/research funding and travel support from Photocure; consulting/advisory fees from Photocure, Pacific Edge, Ferring, Bristol Myers Squibb, Janssen, Johnson & Johnson, Protara, Urogen, Pfizer, CG Oncology, Vesica Health, and ImmunityBio; and has stock/other ownership interests in Taris. Ashish M. Kamat has served as a consultant for Abbott Molecular, Arquer, ArTara, Asieris, Astra Zeneca, BioClin Therapeutics, Biological Dynamics, Bristol Myers Squibb, Cepheid, Cold Genesys, Eisai, Engene, Ferring, FerGene, Imagin, Incyte DSMB, Janssen, MDxHealth, Medac, Merck, Pfizer, Photocure, ProTara, Roviant, Seattle Genetics, Sessen Bio, Theralase, TMC Innovation, US Biotest, and Urogen; and has contracted research with Adolor, Bristol Myers Squibb, FerGene, FKD Industries, Heat Biologics, Merck, Photocure, and SWOG/NIH and patents with CyPRIT (Cytokine Predictors of Response to Intravesical Therapy) Joint with UT MD Anderson Cancer Center. Neal D. Shore has received grants/research funding from AbbVie, Advantagene, Amgen, Aragon Pharmaceuticals, Astellas, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, CG Oncology, Clovis Oncology, Dendreon, DisperSol, Endocyte, Exact Imaging, Exelixis, Ferring, FKD Therapies, Forma Therapeutics, Foundation Medicine, Genentech, Guardant Health, InVitae, Istari Oncology, Janssen, Jiansu Yahong Meditech, MDxHealth, Medivation, Merck, MT Group, Myovant Sciences, Myriad, Novartis, Nymox, OncoCellMDx, ORIC Pharmaceuticals, Pacific Edge, Palette Life Sciences, Plexxikon, Pfizer, Point Biopharma, Propella Therapeutics, RhoVac, Sanofi, Seattle Genetics, Sesen Bio, Steba Biotech, Theralase, Tolmar, Urogen, Urotronic, US Biotest, Vaxiion, Veru, and Zenflow; consulting/advisory fees from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, CG Oncology, Clarity Pharmaceuticals, Clovis Oncology, Dendreon, Exact Imaging, FerGene, Ferring, Foundation Medicine, Genesis Cancer Care, Genzyme, InVitae, Janssen, Lantheus, Lilly, MDxHealth, Medivation, Myovant Sciences, Myriad Genetics, Nymox, Pacific Edge Biotechnology, Peerview, Pfizer, Phosphorus, Photocure, Propella Therapeutics, Sanofi, Sema4, Sesen Bio, Specialty Networks, Telix Pharmaceuticals, Tempus, Tolmar, Urogen, and Vaxiion; and honoraria/speaker fees from Astellas, AstraZeneca, Bayer, Clovis Oncology, Dendreon, Foundation Medicine, Guardant Health, Janssen, Merck, and Pfizer. Joshua J. Meeks has received honoraria from Astellas Pharma, AstraZeneca, Imvax, Incyte, Janssen, Merck, Pfirzer, Prokarium, Urogen Pharma; research funding from Epizyme and Merck Sharp & Dohme; has patents, royalties, or other intellectual property (institutional) : NMIBC classifier, TCGA classifier; and has a relationship (undefined) with Olympus. Matthew D. Galsky has served as a consultant for Abbvie Inc, Alligator, Astellas Pharma, AstraZeneca, Basilea, Bicycle, Bristol Myers Squibb, Curis, Dracen, Dragonfly, EMD Serono, FujiFilm Holdings America Corporation, Genentech, Gilead Sciences, GlaxoSmithKline, Incyte Corp, Janssen Biotech, Merck, Numab, Pfizer, Rappta Therapeutics, Seattle Genetics, and Veracyte. Joseph M. Jacob has received consulting or advisory fees from Janssen, Photocure, Urogen, and Verity Pharmaceuticals. Michiel S. van der Heijden has served as a consultant (paid to institution) for Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Janssen, MSD Oncology, Pfizer, Roche, and Seagen; and has received institutional research funding from 4SC, AstraZeneca, Bristol Myers Squibb, and Roche. Stephen B. Williams has no disclosures to report. Thomas Powles has received consulting fees from Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Incyte, Ipsen, Johnson & Johnson, Mash Up Ltd, Merck Serono, MSD, Novartis, Pfizer, Roche, and Seattle Genetics; grant support from Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Ipsen, Johnson & Johnson, Merck Serono, MSD, Novartis, Pfizer, Seattle Genetics, and Roche; and support for attending meetings and/or travel from AstraZeneca, Ipsen, MSD, Pfizer, and Roche. Sam S. Chang has served as a consultant for ImmunityBio, Janssen, Merck, Pfizer, and Uro Urogen; Vanderbilt University Medical Center is a trial site for TAR-200. James W. F. Catto has received honoraria from AstraZeneca, Bristol Myers Squibb, and Roche; consultant fees from AstraZeneca, Bristol Myers Squibb, Ferring, Gilead Sciences, Ipsen, Janssen, QED Therapeutics, Photocure, Roche, and Steba Biotech; and institutional grants from Roche; has participated in a data safety monitoring board or advisory board for Bristol Myers Squibb; and is an unpaid trustee for Fight Bladder Cancer UK and Weston Park Cancer Charity. Sarah P. Psutka has had a consulting or advisory role with Janssen, Medtronic, and Merck; and has received honoraria from AstraZeneca. Félix Guerrero-Ramos has received grants/research funding from Combat Medical; consulting/advisory fees from AstraZeneca, Bristol Myers Squibb, Combat Medical, and Janssen; honoraria/speaker fees from Combat Medical, Janssen, and Pfizer; and travel support from Ipsen and Pfizer. Evanguelos Xylinas has received grants/research funding from Ferring; and consulting/advisory fees from Boston Scientific, Ipsen, Janssen Oncology, MSD, Astellas, AstraZeneca, and Bristol Myers Squibb. Makito Miyake has no disclosures to report. Giuseppe Simone has no disclosures to report. Karen Daniel, Hussein Sweiti, and Christopher Cutie are employees of Janssen Research & Development and may have stock/stock options with Johnson & Johnson. Andrea Necchi has served as a consultant or advisor for Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Incyte, Janssen, Merck, Pfizer, and Roche; and has received institutional grant support from Bristol Myers Squibb, Gilead Sciences, and Merck., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the oncological efficacy and safety of sequential intravesical gemcitabine/docetaxel (Gem/Doce) therapy in a European cohort of patients with high-risk and very-high-risk non-muscle-invasive bladder cancer (NMIBC) after previous Bacillus Calmette-Guérin (BCG) treatment., Materials and Methods: Data were retrospectively collected from 95 patients with NMIBC, treated with Gem/Doce at 12 European centres between 2021 and 2024. Patients previously treated with BCG who had completed a full induction course and received at least one follow-up evaluation were included. One-year disease-free survival (DFS), high-grade DFS and progression-free survival (PFS) were estimated using Kaplan-Meier curves. Adverse events (AEs) were recorded through medical interviews., Results: Of 75 patients, 63 (84%) were classified as having high-risk and 12 (16%) as having very-high-risk NMIBC. Over a median (interquartile range) follow-up of 9 (5-14) months, 20 patients (27%) relapsed and five (6.7%) underwent radical cystectomy. The 1-year DFS was 73% (95% confidence interval [CI] 62-86%), 1-year high-grade DFS was 79% (95% CI 68-91%) and 1-year PFS was 95% (95% CI 90-100%). AEs occurred in 34 patients (45%), with six (8.7%) experiencing severe AEs. Limitations of the study include the short follow-up and variability in both treatment dwelling times and dosage across centres., Conclusion: The intravesical Gem/Doce regimen demonstrated promising short-term oncological outcomes and was well tolerated in this cohort of patients with high- and very-high-risk NMIBC previously treated with BCG. Prospective studies and randomised trials are awaited to define the ideal candidates for Gem/Doce therapy and to standardise treatment protocols., (© 2025 BJU International.)

Background and Objective: Given the uncertainty regarding the role of radical nephroureterectomy (RNU) as part of a multimodal treatment strategy for upper tract urothelial carcinoma (UTUC) patients with cN+ disease, we aimed to perform a systematic review and meta-analysis of the corresponding literature., Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 17 observational comparative and noncomparative studies, published between January 2000 and September 2024, evaluating UTUC patients with cTanyN+M0 disease (P) who received RNU as part of a multimodal treatment strategy (I), as compared with any treatment strategy if applicable (C), to assess oncological or postoperative outcomes (O). Meta-analyses were further performed, as appropriate., Key Findings and Limitations: Overall, 15 studies evaluated the effectiveness of adding chemotherapy to RNU in the perioperative setting without specifying the exact timing of delivery (n = 1), in the induction setting (n = 14), or in the adjuvant setting (n = 5), while two studies evaluated the effectiveness of adding RNU to chemotherapy. Meta-analyses showed that the use of induction chemotherapy plus RNU versus RNU alone was associated with greater odds of pathological downstaging (risk ratio [RR] = 3.06; 95% confidence interval [CI] = [2.48-3.77]; p < 0.001; I 2  = 0%; p = 0.44) and pathological complete nodal response (RR = 2.80; 95% CI = [2.03-3.86]; p < 0.001; I 2  = 0%; p = 0.47) as well as prolonged overall survival (HR = 0.52; 95% CI = [0.42-0.64]; p < 0.001; I 2  = 14%; p = 0.33) without any significant impact on the risk of overall (RR = 1.14; 95% CI = [0.79-1.64]; p = 0.48; I 2  = 0%; p = 0.76) and major (RR = 0.48; 95% CI = [0.18-1.24]; p = 0.13; I 2  = 0%; p = 0.87) postoperative complications. In addition, the use of induction chemotherapy plus RNU versus RNU plus adjuvant chemotherapy (HR = 0.58; 95% CI = [0.38-0.89]; p = 0.01) or chemotherapy alone (HR = 0.49; 95% CI = [0.32-0.76]; p = 0.001; I 2  = 46%; p = 0.17) was associated with prolonged overall survival. Limitations include the observational design of all included studies., Conclusions and Clinical Implications: The use of RNU could provide the greatest oncological benefits without any significant harm in selected UTUC patients with fit general condition and resectable cN+ disease responding to induction chemotherapy., Patient Summary: In this report, we looked at the outcomes of radical surgery in combination with systemic chemotherapy for upper tract urothelial carcinoma with clinical evidence of dissemination to the surrounding lymph nodes. We observed that the use of radical surgery was associated with the greatest oncological benefits without any increased risk of postoperative complications in patients with fit general condition and resectable disease responding to induction chemotherapy. We conclude that the use of induction chemotherapy plus radical surgery could be the best multimodal treatment strategy for these patients., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)