Clinical genitourinary cancer最新文献

{"title":"Comparisons of Pembrolizumab Plus Lenvatinib, Nivolumab Plus Cabozantinib, and Cabozantinib Monotherapy in Advanced Non-Clear Cell Renal Cell Carcinoma Based on Individual Patient Data Reconstruction","authors":"Wei Chen ,&nbsp;Hajime Tanaka ,&nbsp;Soichiro Yoshida ,&nbsp;Shunya Matsumoto ,&nbsp;Masaki Kobayashi ,&nbsp;Shohei Fukuda ,&nbsp;Hiroshi Fukushima ,&nbsp;Yuma Waseda ,&nbsp;Yasuhisa Fujii","doi":"10.1016/j.clgc.2025.102458","DOIUrl":"10.1016/j.clgc.2025.102458","url":null,"abstract":"<div><h3>Introduction</h3><div>The optimal treatment strategy for advanced non-clear cell renal cell carcinoma (nccRCC) remains unclear. This study compares the efficacy of pembrolizumab plus lenvatinib (Pem+Len), nivolumab plus cabozantinib (Nivo+Cabo), and cabozantinib monotherapy (Cabo) for advanced nccRCC.</div></div><div><h3>Patients and Methods</h3><div>A systematic literature search was conducted to identify clinical trials investigating the 3 treatment regimens for advanced nccRCC. Individual patient data (IPD) were reconstructed from Kaplan–Meier curves for progression-free survival (PFS) and overall survival (OS) using the IPDfromKM package. The outcomes were compared across treatment regimens. A subgroup analysis was conducted for papillary RCC (pRCC).</div></div><div><h3>Results</h3><div>Three clinical trials (NCT02761057, NCT03635892, and NCT04704219) were included; 242 patients were analyzed, including 158/40/44 patients receiving Pem+Len/Nivo+Cabo/Cabo, respectively. Patients with pRCC accounted for 59%/80%/100% of each treatment cohort, respectively. Pem+Len yielded significantly superior PFS (HR = 0.52, 95% CI, 0.34-0.81, <em>P</em> &lt; .01) and OS (HR = 0.50, 95% CI, 0.28-0.89, <em>P</em> = .02) compared with Cabo. Nivo+Cabo showed potential superiority over Cabo in PFS (HR = 0.73, 95% CI, 0.44-1.20, <em>P</em> = .21) and OS (HR = 0.64, 95% CI, 0.35-1.16, <em>P</em> = .14), although these differences did not reach statistical significance. Our analysis did not reveal a clear superiority/inferiority between Pem+Len and Nivo+Cabo. The subgroup analysis for pRCC demonstrated significantly better PFS with Pem+Len (HR = 0.48, 95% CI, 0.29-0.77, <em>P</em> &lt; .01) compared with Cabo, while the benefit of Nivo+Cabo was not significant (HR = 0.66, 95% CI, 0.37-1.15, <em>P</em> = .14). Limitations included its retrospective design and inconsistent follow-up periods among the trials.</div></div><div><h3>Conclusions</h3><div>The IPD reconstruction analysis suggested better PFS and OS with Pem+Len and Nivo+Cabo compared with Cabo, supporting the use of these combination therapies for advanced nccRCC. Further comparative studies are needed to validate these findings.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102458"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Impact of Biopsy Gleason 4 + 5, 5 + 4, and 5 + 5 in Grade Group 5 after Radical Prostatectomy","authors":"Yu Ozawa ,&nbsp;Rohan Sharma ,&nbsp;Marcio Covas Moschovas ,&nbsp;Marco Sandri ,&nbsp;Shady Saikali ,&nbsp;Ari Diamond ,&nbsp;Travis Rogers ,&nbsp;Vipul Patel","doi":"10.1016/j.clgc.2025.102441","DOIUrl":"10.1016/j.clgc.2025.102441","url":null,"abstract":"<div><h3>Background</h3><div>Grade Group 5 (GG5) subtypes exhibit prognostic heterogeneity, but evidence remains limited, and mainly derived from population-based studies. We evaluated their impact on oncologic outcomes following radical prostatectomy (RP).</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 892 patients with biopsy-confirmed GG5 prostate cancer who underwent robot-assisted RP by a single surgeon between 2015 and 2024. Oncologic outcomes were compared among GG5 subtypes: Gleason score (GS) 4 + 5 (n = 688), 5 + 4 (n = 149), and 5 + 5 (n = 55). Primary endpoints were PSA persistence and biochemical recurrence (BCR). PSA persistence was assessed using multivariable logistic regression adjusting for potential confounders including age, race, PSA at diagnosis, clinical T stage, positive core rate, neoadjuvant hormonal therapy, and year of surgery. BCR was evaluated using Kaplan–Meier and log-rank analyses, followed by multivariable Cox regression with the same covariates.</div></div><div><h3>Results</h3><div>Despite neoadjuvant hormonal therapy in 614 patients with comparable distribution across subtypes, organ-confined disease was observed in only 24% (211/892) following RP. PSA persistence occurred in 117 patients. During a median follow-up period of 36 months (Interquartile range: 18-60), BCR occurred in 242 patients, while 326 were followed up without PSA persistence or BCR for at least 60 months. Significant differences in BCR were observed among 3 subtypes (<em>P</em> = .028). Both GS 5 + 4 and 5 + 5 were independent predictors of PSA persistence (adjusted ORs: 1.80 [95% CI 1.08–3.01] and 2.33 [95% CI 1.08–5.02], respectively). GS 5 + 5 was significantly associated with BCR (adjusted HR 2.15 [95% CI 1.29–3.58]), whereas GS 5 + 4 was not (adjusted HR 1.30 [95% CI 0.94–1.81]). The main limitation was the relatively short follow-up.</div></div><div><h3>Conclusions</h3><div>Our study highlights the clinical relevance of GG5 subtyping within a cohort treated with a consistent surgical technique. Among these subtypes, GS 5 + 5 confers the highest risk of PSA persistence and BCR following RP. These findings support biopsy interpretation and preoperative counseling, particularly regarding multimodal treatment strategies for the highest-grade prostate cancer.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102441"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Evaluation of Androgen Receptor Pathway Inhibitors in Metastatic Castration-Sensitive Prostate Cancer: A Multicenter Inverse Probability of Treatment Weighting-Based Study","authors":"Keita Kobayashi ,&nbsp;Takanori Tokunaga ,&nbsp;Kazuhiro Nagao ,&nbsp;Koki Fujikawa ,&nbsp;Kazuo Oba ,&nbsp;Kimio Takai ,&nbsp;Hiroaki Matsumoto ,&nbsp;Shigeru Sakano ,&nbsp;Satoshi Shirataki ,&nbsp;Yasuhide Tei ,&nbsp;Masanori Tabara ,&nbsp;Satoru Yoshihiro ,&nbsp;Seiji Yano ,&nbsp;Hideaki Ito ,&nbsp;Seiji Kitahara ,&nbsp;Chietaka Ohmi ,&nbsp;Jumpei Akao ,&nbsp;Koji Shiraishi","doi":"10.1016/j.clgc.2025.102437","DOIUrl":"10.1016/j.clgc.2025.102437","url":null,"abstract":"<div><h3>Introduction</h3><div>Androgen receptor pathway inhibitor (ARPI) plus androgen deprivation therapy (ADT) is a guideline-endorsed standard for metastatic castration-sensitive prostate cancer (mCSPC). Robust comparative data on individual ARPIs and their subsequent management after castration resistance remain limited.</div></div><div><h3>Methods</h3><div>This multicenter retrospective study included consecutive patients who received first-line ARPI for mCSPC between January 2018 and December 2023. Inverse probability of treatment weighting (IPTW) balanced the baseline clinicopathological variables across the abiraterone (<em>n</em> = 136), enzalutamide (<em>n</em> = 80), and apalutamide (<em>n</em> = 58) cohorts. PSA response subgroups were defined as early response (PSA &lt;0.2 ng/mL by 3 months and sustained for 12 months), delayed response (first attainment ≥6 months, sustained for 12 months), early relapse (attainment but rebound ≥0.2 ng/mL within 12 months), and nonresponse (no attainment).</div></div><div><h3>Results</h3><div>Among 274 evaluable male patients, apalutamide yielded more grade ≥2 toxicities and dose modifications, although grade ≥3 events were comparable across arms. After IPTW, time to castration-resistant prostate cancer (CRPC) and overall survival (OS) did not differ among the ARPIs (<em>P</em> = .657, <em>P</em> = .286), and PSA ≤0.2 ng/mL conversion rates at 1, 3, 6, and 12 months were similar. Patients with early and delayed responses showed equivalent times to CRPC, whereas patients with early relapse and nonresponse experienced a significantly shorter time to CRPC and OS (<em>P</em> &lt; 0.001). Eighty-one patients developed CRPC; first-line docetaxel (<em>n</em> = 35) and ARPI (<em>n</em> = 26) achieved comparable OS (<em>P</em> = .849).</div></div><div><h3>Conclusion</h3><div>The efficacies of abiraterone, enzalutamide, and apalutamide were equivalent if the baseline imbalances were mitigated. Sustained PSA suppression &lt;0.2 ng/mL for 12 months predicts favorable outcomes, regardless of the speed of decline, whereas failure to achieve or maintain this threshold is associated with poorer prognosis. The choice between docetaxel and alternative ARPI for first-line treatment of metastatic CRPC showed no survival differences.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102437"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rates of Secondary Bladder and Rectal Cancers After External Beam Radiation for Prostate Cancer According to Age and D’amico Risk Groups in A Contemporary Cohort","authors":"Mario de Angelis ,&nbsp;Carolin Siech ,&nbsp;Letizia Maria Ippolita Jannello ,&nbsp;Francesco Di Bello ,&nbsp;Natali Rodriguez Peñaranda ,&nbsp;Pietro Scilipoti ,&nbsp;Mattia Longoni ,&nbsp;Jordan A. Goyal ,&nbsp;Zhe Tian ,&nbsp;Nicola Longo ,&nbsp;Ottavio de Cobelli ,&nbsp;Gennaro Musi ,&nbsp;Felix K.H. Chun ,&nbsp;Stefano Puliatti ,&nbsp;Fred Saad ,&nbsp;Shahrokh F. Shariat ,&nbsp;Giorgio Gandaglia ,&nbsp;Marco Moschini ,&nbsp;Francesco Montorsi ,&nbsp;Alberto Briganti ,&nbsp;Pierre I. Karakiewicz","doi":"10.1016/j.clgc.2025.102429","DOIUrl":"10.1016/j.clgc.2025.102429","url":null,"abstract":"<div><h3>Background</h3><div>External beam radiation therapy (EBRT) predisposes to radiation-induced bladder (BCa) and/or rectal cancer (RCa). This risk may have declined with modern radiation techniques. Moreover, it remains unclear whether the risk varies by age or D’Amico risk classification.</div></div><div><h3>Materials and Methods</h3><div>Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients who were treated with either EBRT or radical prostatectomy (RP) for prostate cancer. Cumulative incidence plots and competing risks regression (CRR) models were fitted. Subgroup analyses were performed according to year of diagnosis (contemporary: 2012-2020 vs. historical: 2004-2011 cohorts), age (&lt; 65 vs. ≥ 65) and D’Amico risk groups.</div></div><div><h3>Results</h3><div>Of 251,838, 110,239 (44%) underwent EBRT versus 141,599 RP (56%). Relative to RP patients, EBRT was associated with a two-fold higher 10-year incidence of secondary BCa (0.9 versus 1.9%, respectively). In multivariable CRR models, EBRT was associated with higher risk of BCa (HR: 1.5, 95% CI: 1.3-1.6, <em>P</em> &lt; .001). Similarly, relative to RP, EBRT was also associated with two-fold higher 10-year incidence of secondary RCa (0.8 versus 1.5%, respectively). In multivariable CRR models, EBRT was associated with higher risk of RCa (HR: 1.4, 95% CI: 1.2-1.5, <em>P</em> &lt; .001). In subgroup analyses, the 5-year EBRT–RP absolute difference in secondary RCa was lower in the contemporary cohort (0.2%) than in the historical cohort (0.5%), whereas no such reduction was observed for BCa. In subgroup analyses according to D’Amico risk groups and age, no clinically significant differences were recorded.</div></div><div><h3>Conclusion</h3><div>EBRT is associated with higher risk of both BCa and RCa as compared to RP. In contemporary EBRT patients, secondary RCa rate is lower, but not BCa rate. D’Amico risk groups as well as age categories did not affect either secondary BCa or secondary RCa rates.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102429"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Penalized-Survival Nomogram Predicts 5-Year Metastasis-Free Survival After Salvage Radiotherapy for Postprostatectomy Patients: A Multicenter Study","authors":"F. Mastroleo ,&nbsp;R. Villa ,&nbsp;M. Zaffaroni ,&nbsp;M.G. Vincini ,&nbsp;C. Franzese ,&nbsp;L. Nicosia ,&nbsp;F. Matrone ,&nbsp;A. Donofrio ,&nbsp;A. Magli ,&nbsp;L. Triggiani ,&nbsp;S. Barra ,&nbsp;G. Timon ,&nbsp;M. Augugliaro ,&nbsp;V. Burgio ,&nbsp;G. Francolini ,&nbsp;M. Hasterok ,&nbsp;M. Miszczyk ,&nbsp;N. Simoni ,&nbsp;C. Spatola ,&nbsp;F. Alongi ,&nbsp;B.A. Jereczek-Fossa","doi":"10.1016/j.clgc.2025.102415","DOIUrl":"10.1016/j.clgc.2025.102415","url":null,"abstract":"<div><h3>Background/Aim</h3><div>Salvage radiotherapy (SRT) is a key treatment for biochemical recurrence (BCR) after radical prostatectomy (RP), yet a significant proportion of patients progress to distant metastasis. This multicenter retrospective study aimed to analyze a series of patients who underwent SRT and to develop a predictive nomogram for 5-year-distant-metastasis-free survival (DMFS).</div></div><div><h3>Material and Methods</h3><div>Data were collected from 15 European centers from June 1, 2022, to September 30, 2024. We included SRT patients due to BCR, following RP and no evidence of distant metastases on imaging. A penalized-survival nomogram was developed and internally validated; external validation was performed using data from the largest center. Patients were stratified into low-, intermediate-, and high-risk groups based on tertiles of the predicted risk score distribution.</div></div><div><h3>Results</h3><div>Data from 1,720 SRT patients were analyzed. BCR after SRT occurred in 620 (37%) patients, while clinical recurrence in 494 (30%) patients. Distant metastases were diagnosed in 228 patients (13%). The 2- and 5- years DMFS rates were 93% (95% CI, 92%-95%) and 84% (95% CI, 81%-86%), respectively. Multivariate analysis identified pT3/pT4 stage (HR 1.54 [95% CI, 1.13-2.13], <em>P</em> &lt; .01), ISUP grade group 4/5 (HR 1.75 [95% CI, 1.30-2.35], <em>P</em> &lt; .01), and SRT &lt;12 months from surgery (HR 1.49 [95% CI, 1.07-2.09], <em>P</em> = .02) as independent predictors of DM. The nomogram achieved a C-index of 0.70 in external validation. Stratification into risk groups showed significant differences in DMFS (<em>P</em> &lt; .01).</div></div><div><h3>Conclusions</h3><div>This externally validated nomogram provides a practical tool for predicting 5-year DMFS in patients undergoing SRT. It enables personalized risk assessment, guiding intensified surveillance and treatment for high-risk patients.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102415"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CABOSEQ 3—Comparison of Cabozantinib versus Sunitinib Following First-Line Nivolumab- Ipilimumab for Metastatic Renal Cell Carcinoma: A Target Trial Emulation Using Real-World Data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)","authors":"Audreylie Lemelin ,&nbsp;David Maj ,&nbsp;Kosuke Takemura ,&nbsp;Devon J. Boyne ,&nbsp;Matthew T. Warkentin ,&nbsp;Darren R. Brenner ,&nbsp;Winson Y. Cheung ,&nbsp;Connor Wells ,&nbsp;Chris Labaki ,&nbsp;Bradley A. McGregor ,&nbsp;Luis Meza Contreras ,&nbsp;Sumanta K. Pal ,&nbsp;Benoit Beuselinck ,&nbsp;Rana R. McKay ,&nbsp;Bernadett Szabados ,&nbsp;Thomas Powles ,&nbsp;Takeshi Yuasa ,&nbsp;Lisa Ludwig ,&nbsp;Toni K. Choueiri ,&nbsp;Daniel Y.C. Heng","doi":"10.1016/j.clgc.2025.102431","DOIUrl":"10.1016/j.clgc.2025.102431","url":null,"abstract":"<div><h3>Background and Objective</h3><div>While the benefit of cabozantinib in metastatic renal cell carcinoma (mRCC) is well established post-tyrosine kinase inhibitor therapy, its comparative effectiveness versus sunitinib after first-line (1L) nivolumab-ipilimumab is uncertain.</div></div><div><h3>Methods</h3><div>A target trial emulation was designed using data from the IMDC to estimate the effect of second-line (2L) cabozantinib versus sunitinib within 18 months of discontinuing 1L nivolumab-ipilimumab on overall survival (OS). Patients diagnosed after January 1, 2017 were followed from initiation of 2L until death or last known contact. Inverse-probability of treatment weighting was used to adjust for hemoglobin, calcium, platelets, and neutrophils at 2L, Karnofsky performance score (KPS) at 2L, time from diagnosis to initiation of 2L, and response to 1L nivolumab-ipilimumab. Treatments were compared using adjusted Kaplan-Meier curves and adjusted hazard ratios (HR) from a Cox regression model. Missing data were addressed with multiple imputation by chained equations. E-values were used to assess the likelihood findings could be explained by residual confounding.</div></div><div><h3>Key Findings and limitations</h3><div>A total of 120 and 121 patients who received cabozantinib or sunitinib after 1L nivolumab-ipilimumab were included. The proportion with a KPS &lt; 80% at 2L (21% vs. 46% <em>P</em> = .001) and the overall response rate to first line therapy (12.7% vs. 17.9% <em>P</em> = .002) differed significantly between cabozantinib and sunitinib. The objective response was 27% for cabozantinib versus 20% for sunitinib with a median time to treatment failure of 8.5 (95% CI: 6.9-12.9) and 4.5 (95% CI: 3.7-5.8) months. Median OS was 21.4 (95% CI: 17.9-NA) months from initiation of cabozantinib and 10.1 (95% CI: 7.6-17.7) months for sunitinib (Adjusted HR 0.44 (95% CI: 0.22-0.86)). The E-value was 2.92, suggesting a low likelihood of findings being due to residual confounding alone.</div></div><div><h3>Conclusions</h3><div>These data provide real-world evidence supporting cabozantinib as a second-line treatment option in mRCC following 1L nivolumab-ipilimumab.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102431"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Upstaging From cT2a-b to pT3a on Overall Survival Among Patients With Renal Cell Carcinoma","authors":"Taylor Goodstein ,&nbsp;Rajvi Goradia ,&nbsp;Arnav Srivastava ,&nbsp;Akshay Sood ,&nbsp;Shawn Dason ,&nbsp;Viraj A. Master ,&nbsp;Eric A. Singer","doi":"10.1016/j.clgc.2025.102422","DOIUrl":"10.1016/j.clgc.2025.102422","url":null,"abstract":"<div><h3>Introduction and objectives</h3><div>Identifying patients with renal cell carcinoma (RCC) who may benefit from adjuvant systemic therapy has proven difficult. Approximately 40% of patients with cT2 tumors will be upstaged to pT3a disease following surgery. These patients, given their large tumor size, may represent a higher risk cohort as compared to patients with concordant T3a staging. We assessed OS among cT2 patients who were upstaged to pT3a compared to their cT3a counterparts with concordant pathologic staging.</div></div><div><h3>Methods</h3><div>Using the National Cancer Database, we identified N0M0 adult patients with cT2a, cT2b, and cT3a RCC who underwent partial or radical nephrectomy and had pT3a disease on final pathology. We categorized patients into 3 groups: (1) cT2a to pT3a, (2) cT2b to pT3a, and (3) cT3a to pT3a. We compared OS between the groups using Kaplan Meier estimates and multivariable analysis using Cox proportional hazards models. Subgroup analysis of overall survival was performed for histology (clear cell vs. non–clear cell).</div></div><div><h3>Results</h3><div>About 11,241 patients met inclusion criteria (3,067 cT2a, 1,893 cT2b, and 6,281 cT3a). Median pathological tumor size was 8.2, 12.2, and 7.1 cm for cT2a, cT2b and cT3a tumors, respectively. 5-year OS was 37% for both cT2a and cT2b disease upstaged to pT3a and 48% for cT3a disease with concordant pathological staging (<em>P</em> &lt; .0001). This finding persisted on multivariable analysis (cT3a HR 0.81 [0.77–0.85], <em>P</em> &lt; .001).</div></div><div><h3>Conclusions</h3><div>Patients who were pathologically upstaged from cT2 to pT3a disease had worse OS compared to patients with concordant staging. Our findings imply that it is reasonable to include well-selected cT2 tumors in the next iteration of perioperative trials.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102422"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Experience With Lenvatinib Plus Everolimus (LEN+EVE) in Patients With Pretreated Advanced Renal Cell Carcinoma (RELEVANCE): A Retrospective, Multicenter Case Series","authors":"Hendrik Eggers ,&nbsp;Ramona Stelmacher ,&nbsp;Martin Bögemann ,&nbsp;Arne Strauß ,&nbsp;Christian Thomas ,&nbsp;Johannes Landmesser ,&nbsp;Stefanie Zschäbitz ,&nbsp;Philipp Ivanyi","doi":"10.1016/j.clgc.2025.102449","DOIUrl":"10.1016/j.clgc.2025.102449","url":null,"abstract":"<div><h3>Introduction</h3><div>Metastatic renal cell carcinoma (mRCC) has a poor prognosis despite recent changes in systemic treatment options. Lenvatinib plus everolimus (LEN+EVE), a combination of 2 targeted therapies, is approved after failure of one prior tyrosine kinase inhibitor (TKI) therapy. Our objective was to evaluate the effectiveness and safety of LEN+EVE therapy in patients with mRCC in a real-world setting.</div></div><div><h3>Patients and Methods</h3><div>This retrospective case series included patients with mRCC treatment with LEN+EVE between August 2016 and December 2021 at 6 academic centers in Germany. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety; all evaluated by local investigator. Subgroup analyses by risk scores, previous therapies, and initial dosing were performed.</div></div><div><h3>Results</h3><div>Eighty-one patients were assessed: median age was 61 years (range 42-80), 81.5% were men, and 80.2% of patients had an ECOG score of 0 or 1. Synchronous metastases were found in 39.5% of patients at initial diagnosis. The International Metastatic RCC Database Consortium (IMDC) risk status was favorable in 16.0%, intermediate in 48.1%, and poor in 16.0% of patients. The median number of treatment lines prior to LEN+EVE was 3 (range 0-7). Median treatment duration with LEN+EVE was 6.1 months (range 0.2-29.2). The ORR was 28.4%, DCR was 61.7%, median OS was 11.3 months (95% CI, 8.7-13.9), and median PFS was 6.5 months (95% CI, 5.4-7.6). Median PFS, OS and ORR were similar across patients with 0-2 versus ≥ 3 previous therapeutic lines and for patients with or without previous immunotherapy. The safety profile was manageable, with 6.2% of patients discontinuing treatment due to treatment-related adverse events.</div></div><div><h3>Conclusions</h3><div>LEN+EVE combination therapy demonstrated high effectiveness in heavily pre-treated, real-world cohort of patients with mRCC and challenging disease characteristics—regardless of treatment line, IMDC risk group, initial dosing, or previous treatment with immunotherapy.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102449"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage Cell and Diagnostic Biomarkers in BLCA: Integrating Machine Learning With Single-Cell Analysis","authors":"Guangliang Che,&nbsp;Xuejun Zhao,&nbsp;Rongtuan Luo,&nbsp;Quanfeng Yu,&nbsp;Xiaofeng Guo,&nbsp;Ke Gao,&nbsp;Kangyu Chen,&nbsp;Erfeng Zhang","doi":"10.1016/j.clgc.2025.102447","DOIUrl":"10.1016/j.clgc.2025.102447","url":null,"abstract":"<div><h3>Introduction</h3><div>Bladder cancer (BLCA) has a poor prognosis and continues to pose a significant challenge for clinicians. Prior studies have demonstrated a close relationship of BLCA with macrophages. However, the key subpopulations and molecular functions of macrophages in BLCA have not been uncovered. It becomes possible to use single-cell sequencing technology to explore macrophage heterogeneity and identify new biomarkers.</div></div><div><h3>Patients and Methods</h3><div>Single-cell analysis, pseudo-time analysis, and cell-to-cell communication analysis were performed using single-cell sequencing data of PBMC, BLCA, and urothelial-derived cells (UDCs) obtained from the Gene Expression Omnibus (GEO). Scale-free network analysis was performed using hdWGCNA to select feature genes. LASSO regression and random forest analysis were performed based on TCGA_BLCA data. A prognostic model was established, which was then validated using the Gene Expression Omnibus (GEO) dataset. In addition, immune infiltration analysis was performed between high-risk and low-risk groups using the CIBERSORT, ESTIMATE algorithms, and the TIDE database.</div></div><div><h3>Results</h3><div>Nine macrophage subtypes were identified through single-cell analysis. 571 macrophage-associated genes were identified via hdWGCNA. Seven key genes, including MYO5A, KCNK6, DNAJB4, DEDD2, NFKBID, PSMB10, and ITPRID2, were selected by integrating LASSO regression and RF analysis. A prognostic model was constructed based on these genes. The high-risk cohort displayed markedly poorer overall survival (OS). The model’s prediction accuracy was verified in an independent group. Immune analysis revealed enhanced immune evasion in the high-risk cohort, potentially facilitating tumor progression and increasing the metastatic capacity of BLCA cells.</div></div><div><h3>Conclusions</h3><div>The prognostic model built on 7 macrophage-linked genes exhibited robust prediction performance in BLCA. The M2 macrophage phenotype was notably enriched in the high-risk cohort and appeared to cause elevated tumor invasiveness. Immune infiltration analysis suggested that the high-risk population showed a weaker response to immune checkpoint inhibitor (ICI) treatment. Among all identified genes, DEDD2 may serve as a promising prognostic biomarker for BLCA.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102447"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Socioeconomic Disparities in Prostate Cancer Presentation: The Impact of ADI on Prostate Cancer Stage at Diagnosis","authors":"Alessandro Bertini ,&nbsp;Anna Tylecki ,&nbsp;Alex Stephens ,&nbsp;Alessio Finocchiaro ,&nbsp;Silvia Viganò ,&nbsp;Nicholas Cusmano ,&nbsp;Arjun Dinesh ,&nbsp;Elnaz Guivatchian ,&nbsp;Giovanni Lughezzani ,&nbsp;Nicolò Buffi ,&nbsp;Ettore Di Trapani ,&nbsp;Vincenzo Ficarra ,&nbsp;Alberto Briganti ,&nbsp;Andrea Salonia ,&nbsp;Francesco Montorsi ,&nbsp;Akshay Sood ,&nbsp;Craig Rogers ,&nbsp;Firas Abdollah","doi":"10.1016/j.clgc.2025.102418","DOIUrl":"10.1016/j.clgc.2025.102418","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the impact of socioeconomic deprivation, as measured by Area Deprivation Index (ADI), on PCa stage at diagnosis in a North-American statewide cohort.</div></div><div><h3>Methods</h3><div>The Michigan Department of Health and Human Services (MDHHS) was queried to identify men aged ≥30 with a confirmed diagnosis of PCa at prostate biopsy between 2004 and 2022. An ADI score was assigned to each patient based on their residential census block group. Individuals were further categorized into quartiles, where the fourth 1 (ADI 75-100) represented those living in the most deprived areas. Logistic regression analysis tested the impact of ADI on diagnosis with NCCN high-risk PCa (T3-T4 or PSA &gt;20 ng/ml or ISUP GG ≥4) or metastatic PCa (N1 or M1) at presentation.</div></div><div><h3>Results</h3><div>We included 78018 patients, 17% of whom were Non-Hispanic Black (NHB). Median (IQR) age was 66 (59-72) years. Patients in the most disadvantage quartile (Q4) were more likely to be NHB (40.1% vs. 5.4%), had higher proportion with PSA&gt;20 ng/ml (10.6 % vs. 5.1%), GG≥4 (55.4% vs. 53.1%), clinical <em>T</em> ≥ 3 (4% vs. 3%) and metastasis (3.3% vs. 1.8%) at diagnostic presentation, compared to those in the least disadvantaged quartile (Q1) (all <em>P</em> &lt; .0001). At MVA, for each 10-unit increase in ADI percentile, the relative odds of being diagnosed with NCCN high-risk and metastatic PCa increases by 2% (95% CI, 1.01-1.02) and 4% (95% CI, 1.02-1.05), respectively. Moreover, when compared to NHW men, NHB men had a 1.16 (95% CI, 1.12-1.22) and a 1.52-fold (95% CI, 1.38-1.68) higher relative odds of being diagnosed with NCCN high-risk PCa and metastatic PCa, respectively (<em>P</em> &lt; .001).</div></div><div><h3>Conclusions</h3><div>Living in more deprived areas was associated with higher relative odds of newly diagnosed PCa with unfavorable features. Our study underscores the silent barrier that socioeconomic deprivation poses to cancer early diagnosis and echo the call for tailored interventions to bridge this gap.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102418"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}