Clinical genitourinary cancer最新文献

{"title":"The 4-cm Rule in Partial Nephrectomy: Analysis of Surgical Selection and Safety Using Japan's National Clinical Database.","authors":"Hiroki Ito, Hiroyuki Yamamoto, Tomomi Kamba, Takashi Kobayashi, Ryuichi Mizuno, Eiji Kikuchi","doi":"10.1016/j.clgc.2026.102687","DOIUrl":"https://doi.org/10.1016/j.clgc.2026.102687","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor size is a crucial prognostic factor in renal cell carcinoma (RCC). The traditional 4-cm cutoff in the tumor-node-metastasis classification was established for oncological prognosis rather than technical feasibility or perioperative safety. This study examined the relationship between tumor size, surgical selection, and perioperative outcomes to reassess the role of this threshold in contemporary practice.</p><p><strong>Patients and methods: </strong>We conducted a retrospective cohort study using Japan's National Clinical Database, including patients undergoing partial nephrectomy (PN) or radical nephrectomy for T1 RCC during 2018 to 2021. Complete-case multivariable logistic regression with generalized estimating equations assessed factors associated with PN selection and 30-day outcomes free from complications or death after PN. Restricted cubic splines were used to examine nonlinear associations with tumor size.</p><p><strong>Results: </strong>Among 36,015 patients in 941 hospitals, including 22,860 undergoing PN, tumor size showed a continuous, near-linear inverse association with the odds of PN selection, without a distinct threshold at 4 cm. Among PN cases, the adjusted odds of remaining free from complications or death decreased with increasing tumor size up to approximately 5 cm, with an apparent plateau thereafter.</p><p><strong>Conclusion: </strong>Tumor size remains important for technical assessment and oncological risk stratification, but the 4-cm cutoff alone is insufficient to guide PN selection. Tumor size was continuously associated with surgical choice, while the apparent safety plateau beyond approximately 5 cm among selected PN cases warrants cautious interpretation. Individualized decision-making should integrate tumor size with anatomical complexity, patient factors, and surgical expertise.</p>","PeriodicalId":93941,"journal":{"name":"Clinical genitourinary cancer","volume":" ","pages":"102687"},"PeriodicalIF":2.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Surgical Enablement in Renal Cell Carcinoma: Systematic Review and Meta-analysis.","authors":"Yucong Chai, Erhao Bao, Bohao Zhong, Chuan Zhang, Liming Zhang, Yuqi Jiang, Jing Wang, Jing Liu","doi":"10.1016/j.clgc.2026.102688","DOIUrl":"https://doi.org/10.1016/j.clgc.2026.102688","url":null,"abstract":"<p><p>Neoadjuvant systemic therapy is increasingly considered for selected patients with localized or locally advanced renal cell carcinoma (RCC) when the intended value is not merely tumor shrinkage but surgical enablement, including partial nephrectomy achievement, venous tumor thrombus downstaging, or simplification of the planned operation. We synthesized the evidence on neoadjuvant or preoperative systemic therapy as a surgical-enabling strategy in RCC. PubMed/MEDLINE, Web of Science Core Collection, the Cochrane Library, and Embase were searched from inception to 1 May 2026. Eligible reports included adults with localized or locally advanced RCC treated with neoadjuvant or preoperative systemic therapy before surgery or surgical reassessment and reporting extractable surgical, radiographic, pathologic, or safety outcomes. Random-effects single-arm meta-analyses used non-overlapping outcome-level denominators. Thirty-four eligible study records were included. Pooled rates were 0.80 for partial nephrectomy achievement, 0.32 for objective response, 0.44 for venous tumor thrombus or Mayo-level downstaging, 0.42 for surgical strategy simplification, and 0.11 for pathologic complete response or ypT0. Grade ≥ 3 treatment-related adverse events occurred at a pooled rate of 0.28; among operated patients, Clavien-Dindo grade ≥ III postoperative complications occurred at a pooled rate of 0.13. Certainty was low or very low. Neoadjuvant systemic therapy may support individualized surgical enablement in selected RCC patients, but current evidence does not justify routine use outside carefully defined multidisciplinary decision-making or prospective trials.</p>","PeriodicalId":93941,"journal":{"name":"Clinical genitourinary cancer","volume":"24 8","pages":"102688"},"PeriodicalIF":2.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth-Differentiation-Factor 15 (GDF15) and Hepcidin as Prognostic Biomarkers for Abiraterone-Treated Metastatic Castration-Resistant Prostate Cancer.","authors":"Till Geisendörfer, Andrea Ulrike Steinbicker, Konstantin Egon Seifert, Lisa Schrader, Dorothée Helène Tiedje, Katrin Schlack, Martin Bögemann","doi":"10.1016/j.clgc.2026.102683","DOIUrl":"https://doi.org/10.1016/j.clgc.2026.102683","url":null,"abstract":"<p><strong>Background: </strong>Since 2004, several agents prolonging OS in mCRPC have expanded the therapeutic spectrum. Abiraterone is part of the standard of care. Nevertheless, CRPC remains fatal, highlighting the need for new biomarkers to customize the constantly growing treatment choices and sequences to individual patients.</p><p><strong>Methods: </strong>We retrospectively analyzed serum and demographic data of 28 consecutive patients with mCRPC treated with abiraterone. Baseline serum GDF15 and hepcidin were measured prior to treatment initiation. Because both biomarkers showed right-skewed distributions, they were analyzed as continuous, natural log-transformed variables in Cox regression analyses. Kaplan-Meier analyses using median splits were performed to visualize survival differences. Associations with PFS and OS were examined using univariate and multivariate Cox regression analyses. Multivariate analysis included GDF15, prostate specific antigen-decline by 50% (PSA50) and visceral metastases.</p><p><strong>Results: </strong>Higher baseline ln-transformed GDF15 levels were associated with shorter PFS (HR 1.6; P = .04) and OS (HR 1.8; P < .01) in univariate analysis. Median split Kaplan-Meier analysis showed shorter PFS (8 vs. 13 months, P < .01) and OS (12 vs. 42 months, P < .01) in patients with higher GDF15. In multivariate analyses GDF15 remained independently associated with OS (HR 1.8; P = .01) after adjustment for PSA50 and visceral metastases, whereas the association with PFS was no longer statistically significant. No significant associations between baseline hepcidin and PFS or OS were found.</p><p><strong>Conclusion: </strong>Higher baseline serum GDF15 was associated with poor outcomes in patients with mCRPC treated with abiraterone. Further validation as a candidate prognostic biomarker in prospective studies involving larger, independent patient cohorts is recommended.</p>","PeriodicalId":93941,"journal":{"name":"Clinical genitourinary cancer","volume":" ","pages":"102683"},"PeriodicalIF":2.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Log Odds of Positive Lymph Nodes as a Novel Prognostic Predictor for Bladder Cancer: A Systematic Review and Meta-Analysis.","authors":"Ali Vaezi, Shervin Mossavarali, Maedeh Raznahan, Mojtaba Haddad, Abolfazl Salari, Mohammad Reza Nowroozi, Erfan Amini","doi":"10.1016/j.clgc.2026.102664","DOIUrl":"https://doi.org/10.1016/j.clgc.2026.102664","url":null,"abstract":"<p><p>Accurate lymph node staging is vital for bladder cancer (BC) prognostication. The log odds of positive lymph nodes (LODDS) is a promising prognostic indicator, but its utility in BC has not been systematically reviewed. This meta-analysis evaluated LODDS prognostic value for survival outcomes in BC patients undergoing radical cystectomy (RC). We searched PubMed, Web of Science, Scopus, and Embase from inception to July 31, 2025 for observational studies assessing LODDS and survival in BC patients post-RC. Two reviewers independently performed study selection, extraction, and quality assessment using Strengthening the Reporting of Observational studies in Epidemiology checklist and Newcastle-Ottawa Scale. Hazard ratios (HR) and 95% confidence intervals (CI) were pooled using random-effects models. The study protocol was registered in International Prospective Register of Systematic Reviews (CRD42023438247). Five retrospective studies (24,978 patients) were included. Continuous LODDS was significantly associated with improved overall survival (OS) (univariable HR = 2.11 [95% CI, 2.02-2.21]; multivariable HR = 1.65 [95% CI, 1.57-1.73]) and cancer-specific survival risk (univariable HR = 2.36 [95% CI, 2.25-2.48]; multivariable HR = 1.65 [95% CI, 1.57-1.73]). Categorical LODDS showed progressively worse OS in the univariable analysis (HR = 3.49 [95% CI, 1.11-10.92]) but no statistical significance in the multivariable analysis (HR = 2.07 [95% CI, 0.88-4.92]), with substantial heterogeneity (I² > 93%). Categorical LODDS application faces challenges due to lack of standardized cutoffs and high heterogeneity across studies. Continuous LODDS is a robust prognostic factor for BC survival post-RC, outperforming traditional metrics. Clinicians may consider incorporating continuous LODDS into risk stratification to identify high-risk patients for intensified surveillance or adjuvant therapy. Categorical LODDS should be used with caution until standardized thresholds are established.</p>","PeriodicalId":93941,"journal":{"name":"Clinical genitourinary cancer","volume":" ","pages":"102664"},"PeriodicalIF":2.7,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged Surgical Waiting Time for Radical Nephroureterectomy Is Associated With Worse Survival Outcomes in Patients With Upper Tract Urothelial Carcinoma.","authors":"Yusuke Motoki, Takeshi Sano, Takashi Yoshida, Takahiro Nakamoto, Junichi Ikeda, Ryuichi Yoshida, Makoto Taguchi, Takao Mishima, Hisanori Taniguchi, Masaaki Yanishi, Hidefumi Kinoshita","doi":"10.1016/j.clgc.2026.102670","DOIUrl":"https://doi.org/10.1016/j.clgc.2026.102670","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to identify a candidate cutoff for surgical waiting time from diagnosis of upper tract urothelial carcinoma to radical nephroureterectomy and compare survival outcomes between early and delayed surgery groups.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed 435 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy without neoadjuvant chemotherapy (June 2004-December 2022). A time-dependent receiver operating characteristic approach was used to identify a candidate cutoff of surgical waiting time, and the patients were categorized into early and delayed surgery groups. Between-group imbalances were adjusted using inverse probability of treatment weighting, and we compared overall survival, cancer-specific survival, and recurrence-free survival. Sensitivity analyses treated waiting time as a continuous variable.</p><p><strong>Results: </strong>By the receiver operating characteristic analysis, 435 patients were classified into early (<43 days) and delayed (≥43 days) surgery groups, comprising 217 and 218 patients, respectively. After inverse probability of treatment weighting adjustment, overall survival was significantly worse in the delayed surgery group than in the early surgery group (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.02-2.00, P = .039) whereas no significant differences were observed in cancer-specific survival (HR 1.39, 95% CI 0.89-2.17, P = .144) or recurrence-free survival (HR 1.44, 95% CI 0.98-2.12, P = .061). Upstaging from clinical <T3 to pathological ≥T3 occurred more frequently in the delayed surgery group than in the early surgery group, but was not statistically significant (26.9% vs. 21.1%, P = .172).</p><p><strong>Conclusion: </strong>A surgical waiting time of ≥43 days from upper tract urothelial carcinoma diagnosis to radical nephroureterectomy was associated with worse overall survival in the primary dichotomized analysis. However, continuous analyses did not show a consistent linear association. Thus, approximately 6 weeks should be regarded as a hypothesis-generating benchmark rather than a universal threshold.</p>","PeriodicalId":93941,"journal":{"name":"Clinical genitourinary cancer","volume":" ","pages":"102670"},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Risk-Adapted Framework for Adjuvant Pembrolizumab Plus Belzutifan in Resected Clear Cell Renal Cell Carcinoma.","authors":"Arighno Das, Brittney H Cotta, Pavlos Msaouel, Surena F Matin, Jose A Karam, Daniel D Shapiro","doi":"10.1016/j.clgc.2026.102679","DOIUrl":"https://doi.org/10.1016/j.clgc.2026.102679","url":null,"abstract":"<p><p>The active-control design of LITESPARK-022 demonstrated improved disease-free survival (DFS) with adjuvant pembrolizumab plus belzutifan compared with pembrolizumab alone but did not directly address the post-nephrectomy comparison of combination therapy versus surveillance. Our objective was to estimate the potential absolute benefit of pembrolizumab and pembrolizumab plus belzutifan against surveillance across baseline recurrence-risk scenarios and to clarify when treatment intensification may be clinically meaningful. Given similar trial designs, we used pembrolizumab as the common anchor between KEYNOTE-564 and LITESPARK-022 and performed an anchored indirect comparison under proportional-hazards and cross-trial transportability assumptions. The estimated DFS hazard ratio for pembrolizumab plus belzutifan versus surveillance was 0.52 (indirect 95% confidence interval, 0.39-0.68). We then translated the relative treatment effects into estimated 24-month DFS probabilities across a range of baseline surveillance risks. Absolute benefit increased substantially as baseline recurrence risk increased. Within LITESPARK-022, combination therapy more than doubled grade ≥ 3 treatment-related adverse events (42.2% vs. 17.9%), an excess incurred independently of baseline risk. These additional events were predominantly anemia and hypoxia, whereas immune-mediated events were not increased. These findings provide a risk-adapted, 2-step framework that first considers whether recurrence risk is sufficiently high to justify adjuvant systemic therapy and then whether the additional efficacy of adding belzutifan justifies additional toxicity. For lower-risk patients, surveillance may remain reasonable and the incremental benefit of adding belzutifan to pembrolizumab may be modest, whereas patients at higher recurrence risk may derive a meaningfully greater absolute DFS benefit from combination therapy.</p>","PeriodicalId":93941,"journal":{"name":"Clinical genitourinary cancer","volume":" ","pages":"102679"},"PeriodicalIF":2.7,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Impact of Diagnostic Delay in Testicular Cancer: A Single-center Mexican Cohort Study With Machine Learning Risk Prediction.","authors":"Mauricio Cantellano-Orozco, Alec Anceno, César A Silva-Mendoza, Victor H Garzón-Ortega, Hirad Hosseini, José R Angulo-Sánchez, Daniel R Magdaleno-Rodríguez, Ricardo Cervantes-Zorrilla, Carlos Martínez-Arroyo, Gerardo Fernández-Noyola, Gustavo Morales-Montor, Mario Ortega-González, Carlos Pacheco-Gahbler","doi":"10.1016/j.clgc.2026.102666","DOIUrl":"https://doi.org/10.1016/j.clgc.2026.102666","url":null,"abstract":"<p><strong>Introduction: </strong>Testicular cancer (TC), though highly curable, can carry significant morbidity and mortality when diagnosis is delayed. Herein, we characterize the distribution and prognostic impact of diagnostic delay on stage at presentation, disease progression, and mortality in a Mexican TC cohort.</p><p><strong>Patients: </strong>We retrospectively analyzed 223 men with histologically confirmed TC treated at a single tertiary referral center in Mexico City between January 2017 and January 2025. The analyzable cohort was defined after excluding patients with incomplete clinical data or fewer than 1 month of post-orchiectomy follow-up.</p><p><strong>Methods: </strong>The primary analysis evaluated associations between diagnostic delay and clinical outcomes, using penalized regression for mortality because of complete separation. Secondarily, 5 machine-learning models were cross-validated to assess whether routine clinical variables improved prediction beyond established prognostic factors.</p><p><strong>Results: </strong>Median age was 26 years; 53.4% had non-seminomatous histology and 25.6% had diagnostic delay > 6 months. All 13 deaths occurred in stage IIIC disease, while 56/57 delayed patients progressed. Mortality was associated with delay > 6 months (OR 10.3), poor-risk IGCCCG disease (OR 17.2), and AFP > 10,000 ng/mL (OR 5.3). Cross-validated AUCs ranged from 0.830 to 0.863, with no consistently superior model.</p><p><strong>Conclusion: </strong>Diagnostic delay > 6 months was strongly associated with advanced disease, progression, and mortality, although this association was largely mediated by stage at presentation. Machine learning models did not identify prognostic information beyond established clinical factors.</p>","PeriodicalId":93941,"journal":{"name":"Clinical genitourinary cancer","volume":" ","pages":"102666"},"PeriodicalIF":2.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative and Clinicopathologic Outcomes of Patients with Young-Onset Renal Cell Carcinoma.","authors":"Salvador Jaime-Casas, Ahmad Imam, Anjaney Kothari, Daniel Jiang, Oluwatimilehin Okunowo, Clayton S Lau, Kevin G Chan, Ali Zhumkhawala, Jonathan Yamzon, Bertram Yuh, Wesley Yip","doi":"10.1016/j.clgc.2026.102667","DOIUrl":"https://doi.org/10.1016/j.clgc.2026.102667","url":null,"abstract":"<p><strong>Introduction: </strong>Young-onset renal cell carcinoma (RCC) exhibits distinct clinicopathologic features. We retrospectively compared outcomes and survival dynamics between young- and older-onset RCC cohorts.</p><p><strong>Patients and methods: </strong>We included RCC patients undergoing partial or radical nephrectomy (2015-2024), categorized as young-(≤ 46 years) or older-onset (> 46 years) based on age at surgery. Outcomes included recurrence-free survival (RFS), overall survival (OS), metastasis-free survival (MFS), and cumulative incidence of RCC-related deaths. Chi-squared/Fisher's and Wilcoxon rank sum test were used for intergroup comparisons, Kaplan-Meier and log-rank tests for estimating oncologic outcomes, and multivariable Cox proportional hazards models for identifying predictors of OS/RFS.</p><p><strong>Results: </strong>Of 812 patients, 109 (13%) had young-onset and 703 (87%) older-onset RCC. Young-onset patients showed higher 5-year OS (92.4% vs. 80.9%). Clinical T2 stage showed worse OS (HR 2.46 [95% CI, 1.53, 3.97]) and RFS (HR 2.81 [95% CI, 1.64, 4.83]). Obesity (HR 0.50 [95% CI, 0.32, 0.79] showed improved OS (all P < .05). Non-RCC mortality was significantly higher in older-onset patients at 1 and 5 years (3.6% vs. 14% and 0.97% vs. 6.3%) compared to young-onset patients. Among older-onset patients, obesity (BMI ≥ 30) demonstrated higher OS at 1 and 5 years (95.5% vs. 94.3% and 84.7% vs. 78.1%) (P = .006). Young-onset patients had a significantly higher frequency of germline alterations in FANCI, POLD1, PTCH1, and RINT1 genes (all P < .05).</p><p><strong>Conclusions: </strong>Young-onset RCC patients demonstrated higher OS and comparable RFS and MFS to patients with older-onset RCC. Obesity was associated with improved OS, suggesting a potential role of metabolic reserve in this group.</p>","PeriodicalId":93941,"journal":{"name":"Clinical genitourinary cancer","volume":" ","pages":"102667"},"PeriodicalIF":2.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dosing, Safety, and Pharmacokinetics of Combination Therapy With Darolutamide, Androgen Deprivation Therapy, and Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer in the ARASENS Study.","authors":"Arash Rezazadeh Kalebasty, Ji Sun, Bertrand Tombal, Maha Hussain, Fred Saad, Karim Fizazi, Cora N Sternberg, E David Crawford, Natasha Littleton, Frank Verholen, Weijiang Zhang, Bart Ploeger, Rui Li, Carsten Zieschang, Matthew R Smith","doi":"10.1016/j.clgc.2026.102663","DOIUrl":"https://doi.org/10.1016/j.clgc.2026.102663","url":null,"abstract":"<p><strong>Introduction: </strong>Darolutamide is a highly potent androgen receptor inhibitor, that is structurally different by design. Darolutamide is approved for treatment of metastatic hormone-sensitive prostate cancer in combination with or without docetaxel. We present dosing, safety, and pharmacokinetic analyses of potential drug-drug interactions in patients in the ARASENS study.</p><p><strong>Patients and methods: </strong>ARASENS was an international, randomized, double-blind, phase 3 study in which patients were randomized 1:1 to receive darolutamide 600 mg or placebo in combination with androgen deprivation therapy (ADT) plus docetaxel.</p><p><strong>Results: </strong>In the 1302 treated patients, median treatment duration was longer with darolutamide versus placebo (41.0 vs. 16.7 months), and most patients completed 6 cycles of docetaxel (darolutamide 87.6%; placebo 85.5%). Treatment-emergent adverse events (TEAEs) led to docetaxel dose reduction in 19.9% and 19.5% and discontinuation in 8.0% and 10.3% of darolutamide and placebo recipients, respectively. The most common TEAE leading to docetaxel dose reduction was decreased neutrophil count (darolutamide 5.4%; placebo 6.0%). Granulocyte colony-stimulating factor use was similar in both groups (darolutamide 42.4%; placebo 44.6%) and was mostly administered after the first dose of docetaxel (41.9%; 44.3%). Docetaxel plasma concentration profiles with and without darolutamide were generally overlapping, indicating that darolutamide had no clinically relevant effect on docetaxel pharmacokinetics. Darolutamide exposure was 10% lower with docetaxel than without docetaxel, which is not considered clinically relevant.</p><p><strong>Conclusion: </strong>Darolutamide can be administered with docetaxel and ADT without clinically relevant drug-drug interactions between darolutamide and docetaxel. Known docetaxel TEAEs were the most common reason for docetaxel dose modification.</p><p><strong>Trial registration number: </strong>NCT02799602 (ARASENS).</p>","PeriodicalId":93941,"journal":{"name":"Clinical genitourinary cancer","volume":" ","pages":"102663"},"PeriodicalIF":2.7,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical Quality and Survival After Radical Cystectomy: Clinical Determinants and Prognostic Value of Tetrafecta Achievement.","authors":"Francesco Ditonno, Alessandro Veccia, Greta Pettenuzzo, Lorenzo De Bon, Alberto Bianchi, Maria Angela Cerruto, Riccardo Bertolo, Alessandro Antonelli","doi":"10.1016/j.clgc.2026.102661","DOIUrl":"https://doi.org/10.1016/j.clgc.2026.102661","url":null,"abstract":"<p><strong>Introduction: </strong>To identify independent predictors of tetrafecta achievement after radical cystectomy (RC) and to assess its prognostic value for survival outcomes.</p><p><strong>Patients and methods: </strong>We queried a prospectively maintained single-center database of consecutive patients undergoing RC for nonmetastatic bladder cancer (2014-2025). Tetrafecta achievement was defined as: lymph node yield ≥16, negative soft tissue surgical margins, no intraoperative blood transfusion, and no 90-day major (Clavien-Dindo ≥III) complications. Predictors of tetrafecta achievement were analyzed using multivariable logistic regression. Time-to-event outcomes (overall survival [OS], cancer-specific survival [CSS], disease-free survival [DFS], local DFS [LDFS], metastasis-free survival [MFS]) were evaluated with Kaplan-Meier estimates and multivariable Cox regression adjusting for age, delayed RC (>90 days), locally advanced disease (≥pT3), nodal involvement, and neoadjuvant chemotherapy.</p><p><strong>Results: </strong>Of 330 eligible patients, 144 (43.6%) achieved tetrafecta. Compared with nonachievers, tetrafecta achievers were younger (median 67 vs. 72 years; P < .001), had lower age-adjusted Charlson Comorbidity Index (5 vs. 6; P = .02), more often had Eastern Cooperative Oncology Group 0 (70.8% vs. 59.1%; P = .028), and less frequently had preoperative hydronephrosis (23.6% vs. 38.7%; P = .004). They more commonly underwent robot-assisted RC (41.7% vs. 22.0%; P < .001) and orthotopic neobladder diversion (P < .001). On multivariable logistic regression, older age (odds ratio [OR] 0.96 [95% CI, 0.94-0.99]; P = .005), hydronephrosis (OR 0.55 [95% CI, 0.33-0.94]; P = .029), and cutaneous ureterostomy (OR 0.15 [95% CI, 0.04-0.53]; P = .003) independently reduced tetrafecta odds. With median follow-up of 34 months, OS was higher among tetrafecta achievers on Kaplan-Meier analysis (log-rank P = .012), whereas CSS, DFS, LDFS, and MFS did not differ (all P > .05). Tetrafecta achievement was not independently associated with any survival endpoint on multivariable Cox models.</p><p><strong>Conclusion: </strong>Tetrafecta achievement after RC is primarily influenced by patient fitness and perioperative course and does not independently predict oncologic outcomes, which remain driven by pathological stage and nodal status.</p>","PeriodicalId":93941,"journal":{"name":"Clinical genitourinary cancer","volume":" ","pages":"102661"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}