European urology oncology最新文献

{"title":"Profiling Fibroblast Growth Factor Receptor 3 Expression Based on the Immune Microenvironment in Upper Tract Urothelial Carcinoma.","authors":"Keisuke Shigeta, Kazuhiro Matsumoto, Sotaro Kitaoka, Minami Omura, Kota Umeda, Yuki Arita, Shuji Mikami, Keishiro Fukumoto, Yota Yasumizu, Nobuyuki Tanaka, Toshikazu Takeda, Shinya Morita, Takeo Kosaka, Ryuichi Mizuno, Satoshi Hara, Mototsugu Oya","doi":"10.1016/j.euo.2024.01.013","DOIUrl":"10.1016/j.euo.2024.01.013","url":null,"abstract":"<p><strong>Background: </strong>Although several studies have shown favorable outcomes in upper tract urothelial carcinoma (UTUC) with fibroblast growth factor receptor 3 (FGFR3) mutations and/or expression, the relationship between immune cell markers and FGFR3 expression remains unknown.</p><p><strong>Objective: </strong>To clarify the FGFR3-based immune microenvironment and investigate biomarkers to predict the treatment response to pembrolizumab (Pem) in patients with UTUC.</p><p><strong>Design, setting, and participants: </strong>We conducted immunohistochemical staining in 214 patients with UTUC. The expression levels of FGFR3, CD4, CD8, CD68, CD163, CD204, and programmed cell death ligand 1 (PD-L1) were examined.</p><p><strong>Intervention: </strong>All UTUC patients underwent radical nephroureterectomy.</p><p><strong>Outcome measurements and statistical analysis: </strong>We assessed the relationship between these immune markers and patient prognosis.</p><p><strong>Results and limitations: </strong>A total of 109 (50.9%) patients showed high FGFR3 expressions and a favorable prognosis compared with the remaining patients. Among the six immune markers, CD8 high expression was an independent favorable factor, whereas CD204 expression was an independent prognostic factor for cancer death. From the FGFR3-based immune clustering, three immune clusters were identified. Cluster A showed low FGFR3 with tumor-associated macrophage-rich components (CD204⁺) followed by a poor prognosis due to a poor response to Pem. Cluster B showed low FGFR3 with an immune hot component (CD8⁺), followed by the most favorable prognosis owing to a good response to Pem. Cluster C showed high FGFR3 expression but an immune cold component, followed by a favorable prognosis due to the high FGFR3 expression, but a poor response was confirmed with Pem.</p><p><strong>Conclusions: </strong>Although most patients exhibit a poor response to Pem, individuals with low FGFR3 expression and immune hot status may benefit clinically from Pem treatment.</p><p><strong>Patient summary: </strong>We conducted immunohistochemical staining to evaluate fibroblast growth factor receptor 3 (FGFR3)-related immune microenvironment by evaluating the expressions of CD4, CD8, CD68, CD163, CD204, and PD-L1 in 214 upper tract urothelial carcinoma patients. We identified three distinct immune clusters based on FGFR3 expressions and found that patients with a low FGFR3 expression but immune hot status received the maximum benefit from an immune checkpoint inhibitor.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":"1338-1349"},"PeriodicalIF":8.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697198","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":"Patient-reported Outcome Measures and Experience Measures After Active Surveillance Versus Radiation Therapy Versus Radical Prostatectomy for Prostate Cancer: A Systematic Review of Prospective Comparative Studies.","authors":"Andrea Alberti, Rossella Nicoletti, Daniele Castellani, Yuhong Yuan, Martina Maggi, Edoardo Dibilio, Giulio Raffaele Resta, Pantelis Makrides, Francesco Sessa, Arcangelo Sebastianelli, Sergio Serni, Mauro Gacci, Cosimo De Nunzio, Jeremy Y C Teoh, Riccardo Campi","doi":"10.1016/j.euo.2024.05.008","DOIUrl":"10.1016/j.euo.2024.05.008","url":null,"abstract":"<p><strong>Background and objective: </strong>Current management options for localized prostate cancer (PCa) include radical prostatectomy (RP), radiotherapy (RT), and active surveillance (AS). Despite comparable oncological outcomes, there is still lack of evidence on their comparative effectiveness in terms of patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). We conducted a systematic review of studies comparing PROMs and PREMs after all recommended management options for localized PCa (RP, RT, AS).</p><p><strong>Methods: </strong>A literature search was performed in the MEDLINE, EMBASE, and Cochrane CENTRAL databases in accordance with recommendations from the European Association of Urology Guidelines Office and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. All prospective clinical trials reporting PROMs and/or PREMs for comparisons of RP versus RT versus AS were included. A narrative synthesis was used to summarize the review findings. No quantitative synthesis was performed because of the heterogeneity and limitations of the studies available.</p><p><strong>Key findings and limitations: </strong>Our findings reveal that RP mostly affects urinary continence and sexual function, with better results for voiding symptoms in comparison to other treatments. RT was associated with greater impairment of bowel function and voiding symptoms. None of the treatments had a significant impact on mental or physical quality of life. Only a few studies reported PREMs, with a high rate of decision regret for all modalities (up to 23%).</p><p><strong>Conclusions and clinical implications: </strong>All recommended treatments for localized PCa have an impact on PROMs and PREMs, but for different domains and with differing severity. We found significant heterogeneity in PROM collection, so standardization in real-world practice and clinical trials is warranted. Only a few studies have reported PREMs, highlighting an unmet need that should be explored in future studies.</p><p><strong>Patient summary: </strong>We reviewed differences in patient reports of their outcomes and experiences after surgical prostate removal, radiotherapy, or active surveillance for prostate cancer. We found differences in the effects on urinary, bowel, and sexual functions among the treatments, but no difference for mental or physical quality of life. Our results can help doctors and prostate cancer patients in shared decision-making.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":"1255-1266"},"PeriodicalIF":8.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179120","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":"Functional Outcomes of Stereotactic Ablative Radiotherapy: There Is Room for Improvement.","authors":"Riccardo Bertolo, Giulio Francolini, Laura Bukavina","doi":"10.1016/j.euo.2024.07.004","DOIUrl":"10.1016/j.euo.2024.07.004","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":"1159-1161"},"PeriodicalIF":8.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859476","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":"Contemporary Diagnosis of Very Low-risk Prostate Cancer in a Multihospital Health Care System.","authors":"Richard Bennett, Eric V Li, Austin Y Ho, Jonathan Aguiar, Ashorne K Mahenthiran, Chalairat Suk-Ouichai, Sai K Kumar, Clayton Neill, Edward M Schaeffer, Anugayathri Jawahar, Hiten D Patel, Ashley E Ross","doi":"10.1016/j.euo.2024.04.015","DOIUrl":"10.1016/j.euo.2024.04.015","url":null,"abstract":"<p><p>The National Comprehensive Cancer Network (NCCN) very low risk (VLR) category for prostate cancer (PCa) represents clinically insignificant disease, and detection of VLR PCa contributes to overdiagnosis. Greater use of magnetic resonance imaging (MRI) and biomarkers before patient selection for prostate biopsy (PBx) reduces unnecessary biopsies and may reduce the diagnosis of clinically insignificant PCa. We tested a hypothesis that the proportion of VLR diagnoses has decreased with greater use of MRI-informed PBx using data from our 11-hospital system. From 2018 to 2023, 351/3197 (11%) men diagnosed with PCa met the NCCN VLR criteria. The proportion of VLR diagnoses did not change from 2018 to 2023 (p = 0.8) despite an increase in the use of MRI-informed PBx (from 49% to 82%; p < 0.001). Of patients who underwent combined systematic and targeted PBx and were diagnosed with VLR disease, cancer was found in systematic PBx regions in 79% of cases and in targeted PBx regions in 31% of cases. When performing both systematic and targeted PBx, prebiopsy MRI-based risk calculators could limit VLR diagnosis by 41% using a risk threshold of >5% for Gleason grade group ≥3 PCa to recommend biopsy; the reduction would be 77% if performing targeted PBx only. These findings suggest that VLR disease continues to account for a significant minority of PCa diagnoses and could be limited by targeted PBx and risk stratification calculators. PATIENT SUMMARY: We looked at recent trends for the diagnosis of very low-risk (VLR) prostate cancer. We found that VLR cancer still seems to be frequently diagnosed despite the use of MRI (magnetic resonance imaging) scans before biopsy. The use of risk calculators to identify men who could avoid biopsy and/or biopsy only for lesions that are visible on MRI could reduce the overdiagnosis of VLR prostate cancer.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":"1179-1182"},"PeriodicalIF":8.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907920","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":"Effect of Radical Prostatectomy on Survival for Men with High-risk Nonmetastatic Prostate Cancer Features Selected According to STAMPEDE Criteria: An EMPaCT Study.","authors":"Daimantas Milonas, Alexander Giesen, Annouschka Laenen, Gaëtan Devos, Alberto Briganti, Paolo Gontero, R Jeffrey Karnes, Piotr Chlosta, Frank Claessens, Gert De Meerleer, Wouter Everaerts, Markus Graefen, Giansilvio Marchioro, Rafael Sanchez-Salas, Bertrand Tombal, Henk Van Der Poel, Hendrik Van Poppel, Martin Spahn, Steven Joniau","doi":"10.1016/j.euo.2024.05.016","DOIUrl":"10.1016/j.euo.2024.05.016","url":null,"abstract":"<p><strong>Background and objective: </strong>A meta-analysis of two randomized STAMPEDE platform trials revealed that 3 yr of abiraterone acetate in addition to androgen deprivation therapy and radiation therapy significantly improved metastasis-free and overall survival (OS) in high-risk nonmetastatic prostate cancer (PCa) and should be considered a new standard of care. The aim of our study was to assess long-term cancer-specific survival (CSS) and OS for surgically treated patients with newly diagnosed nonmetastatic node-negative PCa meeting the STAMPEDE criteria for high risk.</p><p><strong>Methods: </strong>This was a retrospective, multicenter cohort study of patients with European Association of Urology (EAU) high-risk PCa who underwent radical prostatectomy and extended pelvic lymph node dissection. CSS was assessed using cumulative incidence curves and the Kaplan-Meier method was used to evaluate OS. We used a Fine and Gray model to evaluate the prognostic value of STAMPEDE high-risk factors (SHRFs) for CSS, and a Cox proportional-hazards model to assess the association of SHRFs with OS.</p><p><strong>Key findings and limitations: </strong>A total of 2994 patients with EAU high-risk PCa were divided into groups with 0, 1, 2, or 3 SHRFs. The 10-yr survival estimates for patients with 0-1 versus 2-3 SHRFs were 95% versus 82% for CSS and 81% versus 64% for OS (both p < 0.0001). In comparison to patients with 0 SHRFs, hazard ratios were 1.2 (p = 0.5), 3.9 (p < 0.0001), and 5.5 (p < 0.0001) for CSS, and 1.1 (p = 0.4), 2.2 (p < 0.0001), and 2.5 (p = 0.0004) for OS for patients with 1, 2, and 3 SHRFs, respectively.</p><p><strong>Conclusions and clinical implications: </strong>Our results confirm that the STAMPEDE high-risk criteria identify a subgroup of patients with highly aggressive PCa features and adverse long-term oncological outcomes. This population is likely to benefit most from aggressive multimodal treatment. Nevertheless, we have shown for the first time that surgery remains a viable treatment option for patients with STAMPEDE high-risk PCa.</p><p><strong>Patient summary: </strong>Prostate cancer that meets the high-risk definitions from the STAMPEDE trial is an aggressive type of cancer. Our results for long-term cancer control outcomes indicate that surgery is a viable option for the subgroup of patients with this type of prostate cancer.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":"1478-1486"},"PeriodicalIF":8.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598911","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":"Differences in Tumor Gene Expression Profiles Between De Novo Metastatic Castration-sensitive Prostate Cancer and Metastatic Relapse After Prior Localized Therapy.","authors":"Vinay Mathew Thomas, Nicolas Sayegh, Beverly Chigarira, Georges Gebrael, Nishita Tripathi, Roberto Nussenzveig, Yeonjung Jo, Emre Dal, Gliceida Galarza Fortuna, Haoran Li, Kamal Kant Sahu, Ayana Srivastava, Benjamin L Maughan, Neeraj Agarwal, Umang Swami","doi":"10.1016/j.euo.2024.04.013","DOIUrl":"10.1016/j.euo.2024.04.013","url":null,"abstract":"<p><strong>Background and objective: </strong>It has been reported that patients with de novo metastatic castration-sensitive prostate cancer (dn-mCSPC) have worse prognosis and outcomes than those whose cancer relapses after prior local therapy (PLT-mCSPC). Our aim was to interrogate and validate underlying differences in tumor gene expression profiles between dn-mCSPC and PLT-mCSPC.</p><p><strong>Methods: </strong>The inclusion criteria were histologically confirmed prostate adenocarcinoma and the availability of RNA sequencing data for treatment-naïve primary prostate tissue. RNA sequencing was performed by Tempus or Caris Life Sciences, both of which have Clinical Laboratory Improvement Amendments certification. The Tempus cohort was used for interrogation, while the Caris cohort was used for validation. Differential gene expression analysis between the cohorts was conducted using the DEseq2 pipeline. The resulting gene expression profiles were further analyzed using Gene Set Enrichment software to identify pathways with enrichment in each cohort.</p><p><strong>Key findings and limitations: </strong>Overall, 128 patients were eligible, of whom 78 were in the Tempus cohort (dn-mCSPC 37, PLT-mCSPC 41) and 50 were in the Caris cohort (dn-mCSPC 30, PLT-mCSPC 20). Tumor tissues from patients with dn-mCSPC had higher expression of genes associated with inflammation pathways, while tissues from patients with PLT-mCSPC had higher expression of genes involved in oxidative phosphorylation, fatty acid metabolism, and androgen response pathways.</p><p><strong>Conclusions and clinical implications: </strong>Our study revealed upregulation of distinct genomic pathways in dn-mCSPC in comparison to PLT-mCSPC. These hypothesis-generating data could guide personalized therapy for men with prostate cancer and explain different survival outcomes for dn-mCSPC and PLT-mCSPC.</p><p><strong>Patient summary: </strong>We measured gene expression levels in tumors from patients with metastatic castration-sensitive prostate cancer. In patients with metastatic disease at first diagnosis, inflammatory pathways were upregulated. In patients whose metastasis occurred on relapse after treatment, androgen response pathways were upregulated. These findings could help in personalizing therapy for prostate cancer and explaining differences in survival.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":"1462-1468"},"PeriodicalIF":8.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911060","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":"Mortality Risk for Patients with Biopsy Gleason Grade Group 1 Prostate Cancer.","authors":"Derya Tilki, Ming-Hui Chen, Hartwig Huland, Markus Graefen, Anthony V D'Amico","doi":"10.1016/j.euo.2024.06.009","DOIUrl":"10.1016/j.euo.2024.06.009","url":null,"abstract":"<p><strong>Background and objective: </strong>We investigated the association of clinical factors at presentation with the presence of unsampled high-risk prostate cancer (PC) and PC-specific mortality (PCSM) and all-cause mortality (ACM) following radical prostatectomy in patients with biopsy Gleason Grade Group (GGG) 1 PC.</p><p><strong>Methods: </strong>The study population comprised 10228 patients treated for GGG1 PC diagnosed via transrectal ultrasound (TRUS)-guided systematic biopsy (SBx; n = 9248) or combined biopsy (CBx; SBx + TRUS/magnetic resonance image [MRI] fusion biopsy; n = 980) from a cohort study at a university hospital in Hamburg, Germany. We used logistic, Fine and Grays, and Cox multivariable regression methods to calculate the adjusted odds ratio (aOR) of adverse pathology and adjusted hazard ratios (aHRs) for early prostate-specific antigen (PSA) failure (≤18 mo), PCSM, and ACM in relation to each clinical factor.</p><p><strong>Key findings and limitations: </strong>Irrespective of biopsy approach, percent positive biopsies (PPB) >50% and PSA >20 ng/ml were significantly associated with higher risk of adverse pathology (SBx: aOR 1.71 and 3.49; CBx: aOR 1.81 and 2.82, respectively) and early PSA failure (SBx: aHR 1.54 and 4.37; CBx: aHR 2.88 and 7.81, respectively). PPB >50% and PSA >20 ng/ml were also associated with higher risk of PCSM (aHRs 2.56 and 3.71) and ACM (aHRs 1.47 and 2.00) in the SBx group (all p ≤ 0.04). The study is limited by the single-institution cohort design.</p><p><strong>Conclusion and clinical implication: </strong>Maintaining the \"cancer\" classification for patients with GGG1 and either PPB >50% or PSA>20 ng/ml and considering rebiopsy to identify unsampled high-grade disease may minimize the risk of mortality for this subgroup.</p><p><strong>Patient summary: </strong>For patients undergoing non-targeted prostate biopsy, approximately 1 in 12 with a biopsy result of grade group 1 prostate cancer may have more aggressive cancer than the result suggests. A very high PSA (prostate-specific antigen) level (>20 ng/ml) or the presence of grade group 1 cancer in more than 50% of the biopsy samples can identify patients at risk.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":"1520-1526"},"PeriodicalIF":8.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497552","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":"Development and Validation of a Multivariable Nomogram Predictive of Post-Nephroureterectomy Renal Function.","authors":"Patrick J Hensley, Craig Labbate, Andrew Zganjar, Jeffrey Howard, Heather Huelster, Trey Durdin, Jonathan Pham, Lianchun Xiao, Maximilian Pallauf, Kara Lombardo, Ilya Glezerman, Nirmish Singla, Jay D Raman, Jonathan Coleman, Philippe E Spiess, Vitaly Margulis, Aaron M Potretzke, Surena F Matin","doi":"10.1016/j.euo.2024.01.005","DOIUrl":"10.1016/j.euo.2024.01.005","url":null,"abstract":"<p><strong>Background and objective: </strong>The timing of perioperative nephrotoxic chemotherapy for upper tract urothelial carcinoma (UTUC) remains controversial and strongly depends on predicted platinum eligibility after radical nephroureterectomy (RNU). The study objective was to develop and validate a multivariable nomogram to predict estimated glomerular filtration rate (eGFR) following RNU.</p><p><strong>Methods: </strong>This was a multi-institutional retrospective study of patients with UTUC treated with RNU from 2000 to 2020 at seven high-volume referral centers. Use of adjuvant chemotherapy was risk-stratified. Patients were retrospectively randomly allocated 2:1 to discovery and validation cohorts. Discovery data were used to identify independent factors associated with GFR at 1-3 mo after RNU on linear regression, and backward selection was applied for model construction. Accuracy was defined as the percentage of predicted eGFR results within 30% of the corresponding observed eGFR.</p><p><strong>Key findings and limitations: </strong>We included 1100 patients, of whom 733 were in the discovery and 367 were in the validation cohort. Multivariable predictors of postoperative eGFR decline included advanced age (odds ratio [OR] -0.18, 95% confidence interval [CI] -0.28 to -0.08), diabetes (OR -2.38, 95% CI -4.64 to -0.11), and hypertension (OR -2.24, 95% CI -4.16 to -0.32). Factors associated with favorable postoperative eGFR included larger tumor size (OR 10.57, 95% CI 7.4-13.74 for tumors >5 cm vs ≤2 cm) and preoperative eGFR (OR 0.44, 95% CI 0.39-0.49). A composite nomogram predicted postoperative eGFR with good accuracy in both the discovery (80.5%) and validation (78.6%) cohorts. Limitations include exclusion of patients who received neoadjuvant chemotherapy.</p><p><strong>Conclusions: </strong>A nomogram that incorporates ubiquitous preoperative clinical variables can predict post-RNU eGFR and was validated with an independent cohort.</p><p><strong>Patient summary: </strong>We developed a tool that uses patient data to predict eligibility for chemotherapy after surgery to remove the kidney and ureter in patients with cancer in the upper urinary tract.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":"1313-1319"},"PeriodicalIF":8.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671614","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":"Large-scale Prospective Validation Study of a Multiplex RNA Urine Test for Noninvasive Detection of Upper Tract Urothelial Carcinoma.","authors":"Hao Zhang, Yue Xu, Kai Wang, Chaoyue Zheng, Yanfeng Li, Huijie Gong, Changming Liu, Mingxiong Sheng, Qinghua Xu, Yifeng Sun, Jinying Chen, Xiaodong Zhang, Changwen Zhang, Hongxian Zhang, Wei Wang","doi":"10.1016/j.euo.2024.03.005","DOIUrl":"10.1016/j.euo.2024.03.005","url":null,"abstract":"<p><strong>Background: </strong>Current approaches for diagnosis and monitoring of upper tract urothelial carcinoma (UTUC) are often invasive, costly, and not efficient for early-stage and low-grade tumors.</p><p><strong>Objective: </strong>To validate a noninvasive urine-based RNA test for accurate UTUC diagnosis.</p><p><strong>Design, setting, and participants: </strong>Urine samples were prospectively collected from 61 patients with UTUC and 99 controls without urothelial carcinomas, in five clinical centers between October 2022 and August 2023 prior to any invasive test (cystoscope or ureteroscope) or treatment. All samples were analyzed with a urine-based RNA test composed of eight genes (CA9, CCL18, ERBB2, IGF2, MMP12, PPP1R14D, SGK2, and SWINGN). The test results were presented with a risk score for each participant, which was applied to categorize patients into low- or high-risk groups.</p><p><strong>Outcome measurements and statistical analysis: </strong>The diagnosis of UTUC was based mainly on preoperative radiological examination criteria and confirmed by postoperative pathological results. The recursive feature elimination and support vector machine algorithms, χ², and Student t test were used.</p><p><strong>Results and limitations: </strong>The eight-gene urine test accurately detected UTUC patients and controls with an area under the curve (AUC) of 0.901 in a single-center testing cohort (n = 93) and an AUC of 0.926 in a multicenter clinical validation cohort (n = 66). In the merged validation cohort, the eight-gene urine test achieved high sensitivity of 90.16%, specificity of 88.89%, and overall accuracy of 89.38%. Remarkably, excellent performance was achieved in 11 low-grade UTUC patients with accuracy of 100%. However, this study collected the urine of UTUC patients only at a single preoperative time point and did not perform continuous tests during the pathological process of UTUC in the surveillance population.</p><p><strong>Conclusions: </strong>Our results demonstrated that the eight-gene urine test can differentiate accurately between UTUC and other urological diseases with high sensitivity and specificity. In clinical practice, it may be used for identifying UTUC patients effectively, leading to reduced reliance on ureteroscopy and blind surgery.</p><p><strong>Patient summary: </strong>In this study, we investigated a multiplex RNA urine test for noninvasive upper tract urothelial carcinoma (UTUC) diagnosis before treatment. We found that the risk scores derived from the multiplex RNA urine test differed significantly between UTUC patients and corresponding controls.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":"1384-1393"},"PeriodicalIF":8.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206560","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":"Circulating Biomarkers Predictive of Treatment Response in Patients with Hormone-sensitive or Castration-resistant Metastatic Prostate Cancer: A Systematic Review.","authors":"Michael Baboudjian, Arthur Peyrottes, Charles Dariane, Gaëlle Fromont, Jérôme Alexandre Denis, Gaëlle Fiard, Diana Kassab, Sylvain Ladoire, Jacqueline Lehmann-Che, Guillaume Ploussard, Morgan Rouprêt, Philippe Barthélémy, Guilhem Roubaud, Pierre-Jean Lamy","doi":"10.1016/j.euo.2024.05.003","DOIUrl":"10.1016/j.euo.2024.05.003","url":null,"abstract":"<p><strong>Background and objective: </strong>Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa.</p><p><strong>Methods: </strong>We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level.</p><p><strong>Key findings and limitations: </strong>The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to ¹⁷⁷Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB).</p><p><strong>Conclusions and clinical implications: </strong>BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies.</p><p><strong>Patient summary: </strong>We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":"1228-1245"},"PeriodicalIF":8.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186283","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}