European urology oncology最新文献

{"title":"A High Decipher Genomic Risk Score Is Associated with Major Pathological Progression in Patients Undergoing Active Surveillance for Prostate Cancer","authors":"Kevin Shee,&nbsp;William A. Pace,&nbsp;Jonathan J. Song,&nbsp;Brendan L. Raizenne,&nbsp;Janet E. Cowan,&nbsp;Lufan Wang,&nbsp;Samuel L. Washington,&nbsp;Katsuto Shinohara,&nbsp;Hao G. Nguyen,&nbsp;Peter R. Carroll,&nbsp;Matthew R. Cooperberg","doi":"10.1016/j.euo.2026.01.006","DOIUrl":"10.1016/j.euo.2026.01.006","url":null,"abstract":"<div><div>Genomic testing has potential to improve clinical decision-making for men with prostate cancer, but is understudied for active surveillance (AS), the standard management option for favorable-risk disease. We investigated whether Decipher scores are associated with AS outcomes in a cohort of patients on AS with at least two biopsies and a Decipher test. Decipher high-risk was defined as a score ≥0.6. Primary outcomes were any upgrading (any increase in grade group [GG]), major upgrading (GG ≥3), and unfavorable histology on subsequent biopsy. Multivariable Cox proportional-hazards regression models were generated for the cohort of 486 patients. On diagnostic biopsy, 78% had low risk and 22% had intermediate risk according to Cancer of the Prostate Risk Assessment (CAPRA) scores, and 12% had high risk according to Decipher. Decipher scores were associated with major upgrading after adjusting for CAPRA scores (hazard ratio [HR] 3.37, 95% confidence interval [CI] 1.17-9.69); high Decipher risk was associated with major upgrading after adjustment for either the CAPRA score (HR 2.00, 95% CI 1.14–3.49) or clinicodemographic variables (HR 2.65, 95% CI 1.36–5.17). The Decipher score was associated with unfavorable histology after adjustment for the CAPRA score (HR 3.68, 95% CI 1.03–13.08); high Decipher risk was associated with unfavorable histology after adjustment for clinicodemographic variables (HR 4.53, 95% CI 2.03–10.15) but not after adjustment for the CAPRA score. No association was observed for any upgrading. Deintensification of surveillance may be warranted for patients with lower Decipher risk.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 772-776"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzalutamide Plus Metformin Versus Enzalutamide Alone in Metastatic Castration-resistant Prostate Cancer: A Randomized Phase 2 Trial (SAKK 08/14)","authors":"S. Gillessen,&nbsp;K. Gobat,&nbsp;R. Cathomas,&nbsp;N. Fischer,&nbsp;R. Pereira Mestre,&nbsp;T. Hermanns,&nbsp;S.I. Rothschild,&nbsp;N. Mach,&nbsp;W. Mingrone,&nbsp;M. Ciriolo,&nbsp;B. Müller,&nbsp;A. Erdmann,&nbsp;C. Schär,&nbsp;C. Mamot,&nbsp;P. Bohanes,&nbsp;A. Omlin,&nbsp;S. Bastian,&nbsp;K. Ribi,&nbsp;L. Mazzucchelli,&nbsp;J. Barizzi,&nbsp;C. Rothermundt","doi":"10.1016/j.euo.2026.03.001","DOIUrl":"10.1016/j.euo.2026.03.001","url":null,"abstract":"<div><h3>Background and objective</h3><div>The aim of our study is to determine whether the addition of metformin to enzalutamide can improve the outcomes of men with metastatic castration-resistant prostate cancer (mCRPC).</div></div><div><h3>Methods</h3><div>From 2016 to 2021, patients with mCRPC were randomized to receive enzalutamide plus metformin or enzalutamide alone, with body mass index (BMI) as a stratification factor. Primary end point was disease-control rate (DCR) at 15 mo. Secondary end points included event-free survival (EFS), time to prostate-specific antigen progression (TTPSAP) or radiologic progression (TTRP), and overall survival (OS). Post hoc analyses include tumor phosphatase and tensin homolog (PTEN)–protein expression.</div></div><div><h3>Key findings and limitations</h3><div>Enzalutamide plus metformin (<em>n =</em> 84) did not increase DCR or secondary end points compared with enzalutamide alone (<em>n =</em> 82; DCR 52% vs 56%, <em>p =</em> 0.64). Post hoc analysis suggests that addition of metformin to enzalutamide may improve TTPSAP (<em>p =</em> 0.0074) in patients with PTEN-expressing tumor (<em>n =</em> 64), but not in patients with PTEN-negative tumor (<em>n =</em> 65, <em>p</em> &gt; 0.6). Patients who were overweight/obese at baseline (BMI ≥25 kg/m²) had better DCR, OS, EFS, TTPSAP, and TTRP than patients with BMI &lt;25 kg/m², independent of treatment arm (<em>p &lt;</em> 0.009).</div></div><div><h3>Conclusions and clinical implications</h3><div>The addition of metformin to enzalutamide did not improve the study end points in the whole study cohort. PTEN status as a potential predictive biomarker and the obesity paradox warrant further investigation.</div></div><div><h3>Patient summary</h3><div>This study found that adding the diabetes drug metformin to standard treatment with enzalutamide did not improve outcomes in men with advanced prostate cancer. However, men whose tumors express PTEN protein seemed to benefit from metformin. Interestingly, overweight/obese men lived longer than those of normal weight.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 822-832"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extended Follow-up from the Stereotactic Body Radiotherapy for High-risk Localized Carcinoma of the Prostate (SHARP) Consortium: Updated Analysis of 440 Patients","authors":"Luca F. Valle,&nbsp;Tahmineh Romero-Kalbasi,&nbsp;Tommy Jiang,&nbsp;Ritchell van Dams,&nbsp;Donald B. Fuller,&nbsp;Andrew Loblaw,&nbsp;Thomas Kennedy,&nbsp;Sean P. Collins,&nbsp;Vaibhav Sharma,&nbsp;Simeng Suy,&nbsp;Vedang Murthy,&nbsp;Indranil Mallick,&nbsp;Nicholas G. Nickols,&nbsp;Neil Desai,&nbsp;Raquibul Hannan,&nbsp;Nima Aghdam,&nbsp;Irving David Kaplan,&nbsp;Kevin Stephans,&nbsp;Rahul Tendulkar,&nbsp;Steven Lau,&nbsp;Amar U. Kishan","doi":"10.1016/j.euo.2026.03.019","DOIUrl":"10.1016/j.euo.2026.03.019","url":null,"abstract":"<div><h3>Background and objective</h3><div>Most patients with high-risk localized prostate cancer (HRLPC) do not undergo stereotactic body radiotherapy (SBRT) in part because of the limited evidence of long-term outcomes. We report long-term efficacy and toxicity outcomes for men treated with SBRT for HRLPC.</div></div><div><h3>Methods</h3><div>Individual patient data from ten prospective clinical studies evaluating SBRT for HRLPC across nine institutions were pooled in the Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate consortium. The Kaplan-Meier method was used to estimate 5-yr biochemical recurrence (BCR) and distant metastasis (DM), stratified by receipt of intensified treatment (≥12 mo of androgen deprivation therapy [ADT] with extremely dose-escalated [≥8 Gy/fraction] prostate-directed SBRT). The impact of intensified treatment on BCR-free survival and DM-free survival was evaluated using multivariable Cox proportional hazards models. Late Common Terminology Criteria for Adverse Events grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity was analyzed using time-to-event models.</div></div><div><h3>Key findings and limitations</h3><div>In 440 patients with a median follow-up time of 60.4 mo, 5-yr BCR and DM rates were 22% (95% confidence interval [CI] = 17–26%] and 9.2% (95% CI = 6.2–12%), respectively. In the 93 patients (21%) who received intensified treatment, 5-yr BCR and DM rates were 7.4% (95% CI = 1.7–13%) and 3.7% (95% CI = 0–7.9%), respectively. Receipt of intensified therapy was associated with a significant reduction in both BCR (hazard ratio [HR] = 0.38 [95% CI = 0.20–0.74], <em>p</em> = 0.005) and DM (HR = 0.43 [95% CI = 0.18–0.99], <em>p</em> = 0.049). For the overall cohort, 5-yr rates of grade ≥2 GU and GI toxicity were 23% (95% CI = 19–27%) and 10% (95% CI = 7–13%), respectively. Limitations include heterogeneous treatment techniques and the nonrandomized nature of the study.</div></div><div><h3>Conclusions and clinical implications</h3><div>The safety and efficacy profile of SBRT for HRLPC remains favorable at long-term follow-up, and SBRT should be integrated into shared decision-making for treatment of HRLPC.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 860-867"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Profiling of Urothelial Bladder Cancer: Bridging Tumor Biology and Clinical Decision-making","authors":"Constance Thibault,&nbsp;Hélène Blons,&nbsp;Yves Allory,&nbsp;Alia Harba,&nbsp;Mathieu Roumiguié,&nbsp;Thomas Seisen,&nbsp;Gautier Marcq,&nbsp;Anne Sophie Bajeot,&nbsp;Priscilla Leon,&nbsp;Alexandra Masson-Lecomte,&nbsp;Benjamin Pradère,&nbsp;Evanguelos Xylinas,&nbsp;Doriane Prost,&nbsp;Pierre-Etienne Gabriel,&nbsp;Pierre Laurent-Puig,&nbsp;Morgan Rouprêt,&nbsp;Francois Audenet,&nbsp;for the Cancer Committee of The French Association of Urology (CC-AFU)","doi":"10.1016/j.euo.2026.06.012","DOIUrl":"10.1016/j.euo.2026.06.012","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Context&lt;/h3&gt;&lt;div&gt;Bladder cancer ranks among the most common malignancies worldwide, with urothelial carcinoma as the predominant histological type. Its development from normal urothelium to non–muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC) is driven by complex molecular events, including chromosomal aberrations, somatic mutations, and epigenetic dysregulation. Advances in next-generation sequencing (NGS) and transcriptomic profiling have transformed the understanding of urothelial tumor biology and opened new perspectives for precision oncology.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To provide an updated synthesis of molecular profiling in urothelial bladder cancer across disease stages and to discuss its diagnostic, prognostic, and therapeutic relevance.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Evidence acquisition&lt;/h3&gt;&lt;div&gt;We conducted a targeted narrative review based on a structured PubMed search of studies published between January 2000 and February 2026 using the keywords “genomic,” “epigenetic,” “transcriptomic,” and “urothelial bladder cancer.” Eligible publications included original research articles, reviews, and meta-analyses in English. Evidence was synthesized across NMIBC, MIBC, and metastatic disease, focusing on molecular alterations and their clinical relevance.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Evidence synthesis&lt;/h3&gt;&lt;div&gt;Both NMIBC and MIBC present frequent &lt;em&gt;TERT&lt;/em&gt; promoter mutations. NMIBC is further characterized by frequent &lt;em&gt;FGFR3&lt;/em&gt; and &lt;em&gt;PIK3CA&lt;/em&gt; mutations, loss of chromosome 9, and widespread chromatin-remodeling gene alterations. MIBC displays high genomic instability, with recurrent mutations in &lt;em&gt;TP53&lt;/em&gt;, &lt;em&gt;RB1&lt;/em&gt;, and chromatin modifiers, as well as frequent alterations in the RTK/RAS/PI3K pathway. Consensus transcriptomic classifications identify reproducible molecular subtypes (luminal, basal/squamous, stroma rich, and neuroendocrine like), each with distinct biological and clinical behaviors. In metastatic disease, NGS and whole-exome analyses reveal strong concordance with localized tumors, with frequent &lt;em&gt;TP53&lt;/em&gt;, &lt;em&gt;ARID1A&lt;/em&gt;, &lt;em&gt;KMT2D&lt;/em&gt;, &lt;em&gt;RB1&lt;/em&gt;, and &lt;em&gt;FGFR3&lt;/em&gt; alterations and APOBEC mutational signatures. Transcriptomic profiling shows subtype heterogeneity and therapy-induced remodeling. Clinically, only &lt;em&gt;FGFR3&lt;/em&gt; alterations currently guide therapy, with erdafitinib approved by the US Food and Drug Administration and the European Medicines Agency for &lt;em&gt;FGFR3&lt;/em&gt;-altered metastatic disease. Beyond tumor testing, circulating tumor DNA assays show promise for molecular residual disease detection and adjuvant treatment stratification.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Molecular profiling has deepened the understanding of bladder cancer biology and identified potential biomarkers for diagnosis, prognosis, and treatment. However, clinical implementation remains limited, and prospective biomarker-driven trials are needed to establish the role of ge","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 986-996"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re: Martino Pedrani, Alberto De Giorgi, Andrea Gallina, et al. When Patients Refuse Radical Cystectomy: Integrating Trimodality Therapy in the Perioperative ICI/ADC Era. Eur Urol Oncol. 2026;9:743–745. http://dx.doi.org/10.1016/j.euo.2026.04.008","authors":"Kelly M. de Ligt,&nbsp;Sarah P. Psutka,&nbsp;Laura S. Mertens","doi":"10.1016/j.euo.2026.06.016","DOIUrl":"10.1016/j.euo.2026.06.016","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 1021-1022"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Cameron E. Alexander, Ashwin Sachdeva, and Noel W. Clarke’s Letter to Editor Re: Develtere D, Devos G. Metformin in prostate cancer: A negative repurposing story across the disease continuum. Urol Oncol 2026. https://doi.org/10.1016/j.euo.2026.04.014.","authors":"Dries Develtere,&nbsp;Gaëtan Devos","doi":"10.1016/j.euo.2026.06.015","DOIUrl":"10.1016/j.euo.2026.06.015","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Page 1020"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of an AI-based Histologic Prognostic Biomarker in Patients with Non–muscle-invasive Bladder Cancer Using the Prospective Swedish National Register of Urinary Bladder Cancer","authors":"Per-Uno Malmström,&nbsp;Anca Dragomir,&nbsp;Truls Gårdmark","doi":"10.1016/j.euo.2026.07.002","DOIUrl":"10.1016/j.euo.2026.07.002","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 1010-1011"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Long Noncoding RNA–based Classifier for Identifying More Aggressive Low-grade Ta Bladder Cancer with Elevated FGFR3 Activity","authors":"Tran Anh Thu Phung,&nbsp;Rachel Weng,&nbsp;Peter C. Black,&nbsp;Lars Dyrskjøt,&nbsp;Joep J. de Jong,&nbsp;Ewan A. Gibb","doi":"10.1016/j.euo.2026.02.020","DOIUrl":"10.1016/j.euo.2026.02.020","url":null,"abstract":"<div><h3>Background and objective</h3><div>Low-grade, stage Ta (TaLG) non–muscle-invasive bladder cancer (NMIBC) is generally nonaggressive; yet, some patients experience recurrence or progression. We previously identified long noncoding RNA cluster 2 (LC2) as an aggressive TaLG subgroup via consensus clustering, which required a cohort-level analysis. We developed a single-sample transcriptome classifier for patient-level LC2 identification.</div></div><div><h3>Methods</h3><div>Using the UROMOL cohort (<em>n</em> = 276) for training/testing and the Hurst (Stage-stratified molecular profiling of non-muscle-invasive bladder cancer enhances biological, clinical, and therapeutic insight. Cell Rep Med 2021;2:100472) cohort (<em>n</em> = 72) for validation, we performed feature selection via median absolute deviation and nested cross-validation. An elastic net regression model (<em>α</em> = 0.5) was trained using ten-fold cross-validation. Performance was evaluated through a pathway analysis, with prognostic significance assessed by Kaplan-Meier and univariable Cox regression.</div></div><div><h3>Key findings and limitations</h3><div>Biological characterization revealed that LC2 tumors exhibited higher proliferation (G2M/E2F signatures), elevated FGFR3 pathway activity, and reduced sonic hedgehog signaling and immune activity (<em>p</em> &lt; 0.001). The classifier identified 7/72 LC2 tumors in the Hurst cohort. LC2-TaLG patients had significantly worse recurrence-free survival (log-rank <em>p</em> &lt; 0.001). On univariable Cox regression analysis, LC2 status was strongly associated with recurrence (hazard ratio 4.52, 95% confidence interval 1.78–11.5; <em>p</em> = 0.001). LC2-predicted tumors in the Hurst cohort showed similar biological patterns.</div></div><div><h3>Conclusions and clinical implications</h3><div>We developed a single-sample transcriptomic classifier identifying aggressive TaLG NMIBC, demonstrating reproducibility across platforms. If validated, this model has the potential to support clinical decision-making.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 814-821"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Intravesical Bacillus Calmette-Guérin Therapy Following Transurethral En Bloc Resection of Bladder Tumour: Post Hoc Analysis of a Randomised, Multicentre, Phase 3 Trial","authors":"Jeremy Yuen-Chun Teoh,&nbsp;Chris Ho-Ming Wong,&nbsp;Cheung-Hing Cheng,&nbsp;Chiu-Fung Tsang,&nbsp;Joseph Kai-Man Li,&nbsp;Bryan Kwun-Chung Cheng,&nbsp;Wilson Hoi-Chak Chan,&nbsp;Wayne Kwun-Wai Chan,&nbsp;Trevor Churk-Fai Li,&nbsp;Yi Chiu,&nbsp;Man-Chung Law,&nbsp;Clarence Lok-Hei Leung,&nbsp;Brian Sze-Ho Ho,&nbsp;Chris Yue-Kit Lee,&nbsp;Ronald Cheong-Kin Chan,&nbsp;Eddie Shu-Yin Chan,&nbsp;Tsz-Yeung Chan,&nbsp;James Hok-Leung Tsu,&nbsp;Ho-Man Tam,&nbsp;Kin-Man Lam,&nbsp;Chi-Fai Ng","doi":"10.1016/j.euo.2025.09.008","DOIUrl":"10.1016/j.euo.2025.09.008","url":null,"abstract":"<div><div>We conducted a post hoc analysis of the EB-StaR study (NCT02993211) to assess the impact of intravesical bacillus Calmette-Guérin (BCG) therapy following en bloc resection of bladder tumour (ERBT) or standard resection (SR) in patients with non–muscle-invasive bladder cancer (NMIBC). The outcome measures were the 1-yr recurrence and progression rates. Among the 276 patients included in the analysis, 1-yr recurrence rates were 33% (95% confidence interval [CI] 21–43%) in the ERBT alone group versus 41% (95% CI 30–50%) in the SR alone group (<em>p</em> = 0.02); and 5% (95% CI 0–14%) in the ERBT + BCG group versus 26% (95% CI 5.8–42%) in the SR + BCG group (<em>p</em> = 0.059). The 1-yr progression rates were 0% in the ERBT alone group versus 2% (95% CI 0–4.6%) in the SR alone group (<em>p</em> = 0.13); and 0% in the ERBT + BCG group versus 5.6% (95% CI 0–16%) in the SR + BCG group (<em>p</em> = 0.4). The combination of ERBT and intravesical BCG therapy appeared to yield excellent oncological control, resulting in a 1-yr recurrence rate of 5% among patients with high-risk NMIBC. Good-quality surgery plus good adjuvant therapy should be considered vital components in optimising long-term oncological outcomes in NMIBC.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 761-765"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Open-label, Phase 1 Dose-finding Study of Single-agent IMU-935, a Novel RORγ/RORγt Inverse Agonist, in Patients with Progressive Metastatic Castration-resistant Prostate Cancer","authors":"Rafael Grochot,&nbsp;Christina Guo,&nbsp;Suzanne Carreira,&nbsp;Mateus Crespo,&nbsp;Jon Welti,&nbsp;Susana Miranda,&nbsp;Ines Figueiredo,&nbsp;Claudia Bertan,&nbsp;Jan Rekowski,&nbsp;Wei Yuan,&nbsp;Nina Tunariu,&nbsp;Katarzyna Abramowicz,&nbsp;Ana Ferreira,&nbsp;Ruth Riisnaes,&nbsp;Antje Neeb,&nbsp;Bora Gurel,&nbsp;Maria de Los Dolores Fenor de la Maza,&nbsp;Khobe Chandran,&nbsp;Juliet Carmichael,&nbsp;Daniel Westaby,&nbsp;Johann de Bono","doi":"10.1016/j.euo.2026.02.014","DOIUrl":"10.1016/j.euo.2026.02.014","url":null,"abstract":"<div><h3>Background and objective</h3><div>Retinoic acid receptor–related orphan receptor gamma (ROR<strong>γ</strong>) is frequently overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and, together with retinoic acid–related orphan receptor gamma t (RORγt), can increase androgen receptor (AR) signalling and promote a proinflammatory tumour microenvironment.</div></div><div><h3>Methods</h3><div>In this phase 1 dose-finding study (NCT05124795), men with mCRPC received the oral RORγ/RORγt inverse agonist IMU-935 across three dose levels (150 mg, 300 mg, or 450 mg twice daily). The primary objective was to determine the recommended phase 2 dose according to a Bayesian optimal interval design. Key secondary endpoints included evaluation of pharmacokinetics and pharmacodynamics, as well as antitumour activity in terms of prostate-specific antigen (PSA), circulating tumour cells (CTCs), and responses according to Response Evaluation Criteria in Solid Tumours.</div></div><div><h3>Key findings and limitations</h3><div>Eighteen men received IMU-935. No dose-limiting toxicities (DLTs) or any grade (G) ≥3 adverse events (AEs) were reported. The most common treatment-related AEs (TRAEs) were G1 nausea (<em>n</em> = 4; 22%) and G1 vomiting (<em>n</em> = 3; 17%). The only G2 TRAEs observed were anaemia (<em>n</em> = 2; 11%) and gastroesophageal reflux disease (<em>n</em> = 1; 6%). Overall, six men (33%) had a decrease in CTC level from ≥5 to &lt;5 cells/7.5 ml, while one participant whose tumour had mismatch repair deficiency (MMRd) experienced a ≥50% decline in PSA and radiologically stable disease for &gt;6 mo. The median time to PSA progression was 8 wk (range 2–36 wk), and median radiological progression-free survival was 11 wk (range 3.4–36 wk).</div></div><div><h3>Conclusions and clinical implications</h3><div>IMU-935 was well tolerated with no DLTs. One participant with MMRd mCRPC experienced a PSA response. Overall, however, robust antitumour activity was not observed in this molecularly unselected cohort.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 804-813"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}