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Effect of NSAID Consumption on Renal Cell Carcinoma Prognosis: A Population-Based Study
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2025-02-08 DOI: 10.1016/j.clgc.2025.102311
Ilkka Kemppinen, Antti Pöyhönen, Priit Veskimäe, Thea Veitonmäki, Teuvo Tammela, Teemu J. Murtola

Objective

The objective is to study the effect of NSAID consumption on renal cell carcinoma prognosis.

Methods

In retrospective cohort study patients diagnosed with renal cell carcinoma (RCC) between 1995 and 2015 (n = 7492) were divided into subgroups based on their NSAID use. Multivariate adjusted analyses were performed using cox's regression model to evaluate hazard ratio for RCC mortality. Analyses were conducted separately for acetylsalicylic acid (ASA), COX-2 selective inhibitor (COXIB), and NSAID (including ASA and COXIB) users.

Results

Any NSAID consumption prior to the diagnosis of RCC exhibits a slightly elevated mortality rate compared to individuals who do not consume NSAIDs (HR 1.08, 95% CI 1.00-1.16). Pre- and postdiagnostic ASA and KOKSIB use, as well as postdiagnostic NSAID, ASA, and COXIB use, weren't associated with RCC mortality. Among women, NSAID use elevated RCC mortality both prior to the diagnosis (HR 1.21, 95% CI 1.08-1.36, P = .005) and after the diagnosis (HR 1.15, 95% CI 1.05-1.29, P = .046).

Conclusion

Prediagnostic NSAID consumption slightly elevated RCC mortality. Among women, both pre- and postdiagnostic NSAID use is associated with heightened RCC mortality.
{"title":"Effect of NSAID Consumption on Renal Cell Carcinoma Prognosis: A Population-Based Study","authors":"Ilkka Kemppinen,&nbsp;Antti Pöyhönen,&nbsp;Priit Veskimäe,&nbsp;Thea Veitonmäki,&nbsp;Teuvo Tammela,&nbsp;Teemu J. Murtola","doi":"10.1016/j.clgc.2025.102311","DOIUrl":"10.1016/j.clgc.2025.102311","url":null,"abstract":"<div><h3>Objective</h3><div>The objective is to study the effect of NSAID consumption on renal cell carcinoma prognosis.</div></div><div><h3>Methods</h3><div>In retrospective cohort study patients diagnosed with renal cell carcinoma (RCC) between 1995 and 2015 (<em>n</em> = 7492) were divided into subgroups based on their NSAID use. Multivariate adjusted analyses were performed using cox's regression model to evaluate hazard ratio for RCC mortality. Analyses were conducted separately for acetylsalicylic acid (ASA), COX-2 selective inhibitor (COXIB), and NSAID (including ASA and COXIB) users.</div></div><div><h3>Results</h3><div>Any NSAID consumption prior to the diagnosis of RCC exhibits a slightly elevated mortality rate compared to individuals who do not consume NSAIDs (HR 1.08, 95% CI 1.00-1.16). Pre- and postdiagnostic ASA and KOKSIB use, as well as postdiagnostic NSAID, ASA, and COXIB use, weren't associated with RCC mortality. Among women, NSAID use elevated RCC mortality both prior to the diagnosis (HR 1.21, 95% CI 1.08-1.36, <em>P</em> = .005) and after the diagnosis (HR 1.15, 95% CI 1.05-1.29, <em>P</em> = .046).</div></div><div><h3>Conclusion</h3><div>Prediagnostic NSAID consumption slightly elevated RCC mortality. Among women, both pre- and postdiagnostic NSAID use is associated with heightened RCC mortality.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 3","pages":"Article 102311"},"PeriodicalIF":2.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Isolated Urinary Tract Persistence or Progression in Patients Treated With Immunotherapy for Advanced Urothelial Carcinoma
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2025-02-06 DOI: 10.1016/j.clgc.2025.102312
Pierre-Etienne Gabriel , Hélène Gauthier , Evanguelos Xylinas , Jean-François Hermieu , François Desgrandchamps , Christophe Hennequin , Stéphane Culine , Alexandra Masson-Lecomte , Clément Dumont

Purpose

Emerging therapies including anti-PD-(L)1 immunotherapy have changed paradigms of treatment and improved oncological outcomes of advanced/metastatic urothelial carcinoma (mUC) patients. An emerging challenge in this setting is the management of isolated urinary tract persistence or progression (IUTP) of primary urothelial tumor despite stability or response of metastatic disease to immunotherapy.

Methods

This retrospective monocentric study included all patients treated with single-agent anti-PD-(L)1 for mUC between August 2015 and October 2023. Patients were divided in cohorts of interest depending on primary UC site (lower or upper tract) and previous surgery at the time of immunotherapy initiation. Incidence of IUTP was analyzed in a competitive-risk fashion.

Results

Overall,107 patients with mUC and no previous surgical treatment of primary tumor treated with immunotherapy were at risk of local progression. Among 65 mUC with an untreated bladder primary site, the cumulative incidence rate of IUTP in patients with nonprogressive metastatic disease on immunotherapy was 21.4% and 42.7% at 1 and 2 years, respectively. In responders, half of IUTP were nonmuscle invasive;5 patients, including all 3 with NMIBC, remained free of distant progression after a median follow-up of 12.7 (4.6-41.2) months. In mUTUC, 2 out of 18 patients (11.1%) experienced isolated primary site progression and underwent radical nephroureterectomy, with one patient remaining free of distant progression over 1 year.

Conclusions

These preliminary results show high incidence of IUTP as a progression pattern in mUC patients with clinical benefit of immunotherapy for mUC, highlighting the interest of monitoring the primary tumor and considering local treatment in selected cases, with promising oncological outcomes.
{"title":"Isolated Urinary Tract Persistence or Progression in Patients Treated With Immunotherapy for Advanced Urothelial Carcinoma","authors":"Pierre-Etienne Gabriel ,&nbsp;Hélène Gauthier ,&nbsp;Evanguelos Xylinas ,&nbsp;Jean-François Hermieu ,&nbsp;François Desgrandchamps ,&nbsp;Christophe Hennequin ,&nbsp;Stéphane Culine ,&nbsp;Alexandra Masson-Lecomte ,&nbsp;Clément Dumont","doi":"10.1016/j.clgc.2025.102312","DOIUrl":"10.1016/j.clgc.2025.102312","url":null,"abstract":"<div><h3>Purpose</h3><div>Emerging therapies including anti-PD-(L)1 immunotherapy have changed paradigms of treatment and improved oncological outcomes of advanced/metastatic urothelial carcinoma (mUC) patients. An emerging challenge in this setting is the management of isolated urinary tract persistence or progression (IUTP) of primary urothelial tumor despite stability or response of metastatic disease to immunotherapy.</div></div><div><h3>Methods</h3><div>This retrospective monocentric study included all patients treated with single-agent anti-PD-(L)1 for mUC between August 2015 and October 2023. Patients were divided in cohorts of interest depending on primary UC site (lower or upper tract) and previous surgery at the time of immunotherapy initiation. Incidence of IUTP was analyzed in a competitive-risk fashion.</div></div><div><h3>Results</h3><div>Overall,107 patients with mUC and no previous surgical treatment of primary tumor treated with immunotherapy were at risk of local progression. Among 65 mUC with an untreated bladder primary site, the cumulative incidence rate of IUTP in patients with nonprogressive metastatic disease on immunotherapy was 21.4% and 42.7% at 1 and 2 years, respectively. In responders, half of IUTP were nonmuscle invasive;5 patients, including all 3 with NMIBC, remained free of distant progression after a median follow-up of 12.7 (4.6-41.2) months. In mUTUC, 2 out of 18 patients (11.1%) experienced isolated primary site progression and underwent radical nephroureterectomy, with one patient remaining free of distant progression over 1 year.</div></div><div><h3>Conclusions</h3><div>These preliminary results show high incidence of IUTP as a progression pattern in mUC patients with clinical benefit of immunotherapy for mUC, highlighting the interest of monitoring the primary tumor and considering local treatment in selected cases, with promising oncological outcomes.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 2","pages":"Article 102312"},"PeriodicalIF":2.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520854","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}
引用次数: 0
Sodium-Glucose Cotransporter 2 (SGLT2) as a Potential Biomarker and Target in Papillary Renal Cell Carcinoma
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2025-02-06 DOI: 10.1016/j.clgc.2025.102314
Erman Akkus , Emre Yekedüz , Yüksel Ürün

Background

SGLT2 is selectively expressed in the human kidney. SGLT2 inhibitors have markedly changed diabetes, heart failure, and kidney disease treatment, and are under investigation in cancer. However, the role of SGLT2 in papillary renal cell carcinoma (pRCC) is not known.

Methods

We investigated the SGLT2 gene expression, associated clinical-molecular features, and overall survival (OS) in pRCC. The Cancer Genome Atlas Program and Gene Expression Omnibus data were utilized. mRNA expression z-scores of the SGLT2 gene relative to normal samples (log-RNASeqV2-RSEM, threshold ± 2) were analyzed (low, unaltered, high expression).

Results

273 patients were involved. As per mRNA expression, 180 patients (66%) had low, and the remaining had unaltered expression. High correlation (r > 0.6) with SGLT2 was observed in IRX5, STRIP2, LINC00899, SATB2-AS1, FOXC1, IRX3, SLC22A8, SH3BP5 genes (P < .001,q < 0.001 for all) and with the HIF-2α (r:0.43, P < .001,q < 0.001). Tumor mutational burden (P = .365) and aneuploidy scores (P = .976) did not differ, however, among the genes with the highest alteration frequency, SETD2 alterations (15.63% vs. 1.07%, P < .00, q = 0.046) were more frequent in the unaltered-expression group. Differential protein expression analysis showed highly separated proteins (ERBB2, AR, MAPK14, VHL, TGM2 in the low and SHC1, SQSTM1, MYH14, and CDH1 in the unaltered group). The median OS has not reached the median in both groups [Hazard Ratio(HR) for the unaltered group:2.658, 95% Confidence Interval(CI):1.401-5.043, P = .003]. SGLT2 expression remained a significant prognostic factor in multivariable analysis [HR:2.446 (95%CI: 1.199-4.990), P = .014].

Conclusions

This study reveals the first data that SGLT2 might have a role in pRCC as a pathogenic factor and biomarker. Confirmatory mechanistic studies are needed.
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引用次数: 0
Clinical, Diagnostic and Therapeutic Framework of mHSPC and nmCRPC: A Multidisciplinary Consensus Project of the Italian Society for Uro-Oncology (SIUrO) mHSPC和nmCRPC的临床、诊断和治疗框架:意大利泌尿肿瘤学会(SIUrO)的多学科共识项目。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.clgc.2024.102292
Rolando Maria D'Angelillo , Orazio Caffo , Nicolò Borsellino , Giampiero Cardone , Giuseppe Ferdinando Colloca , Giario Natale Conti , Marzia Del Re , Stefano Fanti , Barbara Alicja Jereczek-Fossa , Alberto Lapini , Giovanni Luigi Pappagallo , Tommaso Prayer Galetti , Sergio Bracarda
The recent evidences provided in metastatic hormone sensitive prostate cancer (nmHSPC) and in nonmetastatic castration resistant (nmCRPC) introduced the possibility to adopt Androgen Receptor Signaling inhibitor (ARSi) alone (both settings) or with chemotherapy (in mHSPC). In daily clinical practice there are some opening questions regarding the inclusion of next generation imaging, mainly PSMA-PET, how integrate local treatment as radiotherapy, how to select patients or drugs in a multiple-choice scenario, and how to manage patients with comorbidities and polypharmacy. These issues led the Italian Society for Uro-Oncology (SIUrO) to develop a consensus project involving all of the most important Italian scientific societies engaged in the multidisciplinary and multiprofessional management of the disease. This paper describes the items and statements approved, with the aim to support clinicians in managing metastatic hormone sensitive and nonmetastatic castration resistant prostate cancer patients.
最近在转移性激素敏感前列腺癌(nmHSPC)和非转移性去势抵抗(nmCRPC)中提供的证据介绍了单独使用雄激素受体信号抑制剂(ARSi)(两种情况)或联合化疗(mHSPC)的可能性。在日常临床实践中,关于下一代影像学(主要是PSMA-PET)的纳入,如何将局部治疗与放疗相结合,如何在多项选择方案中选择患者或药物,以及如何管理合并合并症和多重用药的患者,存在一些悬而未决的问题。这些问题促使意大利泌尿肿瘤学会(SIUrO)制定了一个共识项目,涉及从事该疾病多学科和多专业管理的所有最重要的意大利科学学会。本文描述了批准的项目和声明,旨在支持临床医生管理转移激素敏感和非转移性去势抵抗前列腺癌患者。
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引用次数: 0
Patterns of Failure After Definitive Trimodality Therapy for Muscle-Invasive Bladder Cancer 肌肉浸润性膀胱癌三位一体治疗后的失败模式。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.clgc.2024.102229
Nikhil V. Kotha , Abhishek Kumar , Paul Riviere , Tyler J. Nelson , Edmund M. Qiao , Amirali Salmasi , Rana R. McKay , Jason A. Efstathiou , Brent S. Rose , Tyler F. Stewart

Background

Real-world outcomes, especially patterns of failure, are limited for patients with muscle-invasive bladder cancer (MIBC) treated with trimodality therapy (TMT). We aim to evaluate patterns of failure after TMT for MIBC in a typical heterogeneous population.

Methods

In the national Veterans Affairs database, patients with urothelial histology, MIBC (T2-4a/N0-3/M0) who underwent definitive intent TMT between 2000-2018. Successful TMT was defined as ≥ 50% definitive radiation dose and ≥ 1 cycle chemotherapy. Endpoints of any recurrence, metastatic (nonbladder) recurrence (MR), and local (bladder) recurrence (LR) evaluated in multivariable Fine-Gray models. Times to recurrence calculated from radiation start date.

Results

In 347 patients with MIBC treated with TMT, 65% of patients were deemed ineligible for surgery while 35% were surgically eligible but elected for TMT. Median follow-up time was 77 months. Median overall survival was 32.4 months (95% CI: 28.2-36.7). 154 (44%) patients had no recurrence. 130 (37%) patients developed MR, median time 9.9 months. 117 (34%) patients developed LR, median time 8.7 months. In multivariable models, lymph node positive (LN+) disease (HR:3.31, 95% CI: 1.45-7.55, P < .01) and pretreatment hydronephrosis (HR:1.62, 95% CI:1.11-2.36, P = .01) were associated with higher rates of MR. No patient, tumor, or treatment variables were associated with LR.

Conclusions

Across a multi-institutional and heterogeneous population, TMT is an effective treatment for many real-world patients with MIBC. However, a notable proportion of patients develop MR and/or LR which emphasizes the need for post-treatment surveillance and improved treatment pathways. Identified high risk features (LN+ disease, pretreatment hydronephrosis) and other markers should be further investigated to delineate the patients at high risk of TMT failure who therefore may potentially benefit from augmented treatment, such as additional systemic therapy.
背景:肌肉浸润性膀胱癌(MIBC)患者接受三联疗法(TMT)治疗的实际结果,特别是失败模式,是有限的。我们的目的是评估典型异质人群中mbc TMT后失败的模式。方法:在国家退伍军人事务数据库中,2000-2018年期间接受明确意向TMT的尿路上皮组织学,MIBC (T2-4a/N0-3/M0)患者。TMT成功定义为≥50%的确定放射剂量和≥1个化疗周期。在多变量Fine-Gray模型中评估任何复发、转移性(非膀胱)复发(MR)和局部(膀胱)复发(LR)的终点。从辐射开始日期算起的复发次数。结果:在347例接受TMT治疗的MIBC患者中,65%的患者被认为不适合手术,35%的患者手术符合条件但选择了TMT。中位随访时间为77个月。中位总生存期为32.4个月(95% CI: 28.2-36.7)。154例(44%)患者无复发。130例(37%)患者发生MR,中位时间9.9个月。117例(34%)患者发生LR,中位时间8.7个月。在多变量模型中,淋巴结阳性(LN+)疾病(HR:3.31, 95% CI: 1.45-7.55, P < 0.01)和预处理肾积水(HR:1.62, 95% CI:1.11-2.36, P = 0.01)与mr的较高发生率相关。没有患者、肿瘤或治疗变量与LR相关。结论:在多机构和异质人群中,TMT是许多现实世界中MIBC患者的有效治疗方法。然而,相当比例的患者出现MR和/或LR,这强调了治疗后监测和改善治疗途径的必要性。确定的高风险特征(LN+疾病,预处理肾积水)和其他标记物应进一步研究,以确定TMT失败的高风险患者,因此可能从强化治疗(如额外的全身治疗)中获益。
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引用次数: 0
Adjuvant Immunotherapy in High-Risk Muscle-Invasive Urothelial Cancer: An Updated Meta-Analysis of Randomized Controlled Trials 高危肌肉侵袭性尿路上皮癌的辅助免疫治疗:随机对照试验的最新荟萃分析
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.clgc.2024.102288
Isadora Mamede , Caroliny Silva , Ana Caroline Alves , Joao Pedro Oliveira , Melissa Maia , Caio Dabbous de Liz , Audrey Cabral de Oliveira

Introduction

Neoadjuvant cisplatin-based chemotherapy followed by radical surgery is the standard treatment for muscle-invasive urothelial carcinoma (MIUC). The Checkmate-274 and AMBASSADOR trials have demonstrated improvements in disease-free survival (DFS) with adjuvant immunotherapy. Consequently, this meta-analysis aimed to assess the effectiveness of strategies involving checkpoint inhibitors in managing high-risk MIUC.

Patients and Methods

We searched PubMed, Embase, Cochrane, ClinicalTrials.gov, EAU24, and ASCO GU abstracts for randomized controlled trials (RCTs) comparing adjuvant PD-1 and PD-L1 inhibitors against control (placebo or observation) for MIUC. Outcomes included DFS, grade ≥3 adverse events (AEs), and overall survival (OS). Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis.

Results

In a cohort of 2220 patients from three RCTs, 1,113 (50.14%) underwent adjuvant immunotherapy. This treatment significantly increased DFS (HR 0.76; 95% CI, 0.65-0.90; P < .01), particularly in lower tract tumors (HR 0.71; 95% CI, 0.56-0.91; P < .01). No substantial DFS improvement surfaced in the upper tract subgroup (P = .28) (p-interaction = .01). PD-L1 status (p-interaction = .83) and previous neoadjuvant chemotherapy (p-interaction = .11) did not significantly affect outcomes. However, immunotherapy correlated with higher grade ≥3 AEs (RR 1.47; P < .01), with no notable difference in OS (P = .07).

Conclusions

Adjuvant PD-1/PD-L1 inhibitors notably enhance MIUC DFS, particularly in lower tract tumors, regardless of PD-L1 status. These findings support immunotherapy, especially anti-PD1, as a valuable adjuvant treatment strategy for high-risk MIUC patients.
新辅助顺铂化疗后根治性手术是肌肉侵袭性尿路上皮癌(MIUC)的标准治疗方法。Checkmate-274和AMBASSADOR试验表明,辅助免疫治疗可改善无病生存期(DFS)。因此,本荟萃分析旨在评估涉及检查点抑制剂的策略在管理高风险MIUC中的有效性。患者和方法:我们检索了PubMed, Embase, Cochrane, ClinicalTrials.gov, EAU24和ASCO GU摘要,以比较辅助PD-1和PD-L1抑制剂与对照组(安慰剂或观察)治疗MIUC的随机对照试验(rct)。结果包括DFS、≥3级不良事件(ae)和总生存期(OS)。采用I2统计量评估异质性,采用随机效应模型进行分析。结果:来自3个随机对照试验的2220例患者中,1113例(50.14%)接受了辅助免疫治疗。该治疗显著提高了DFS (HR 0.76;95% ci, 0.65-0.90;P < 0.01),尤其是下道肿瘤(HR 0.71;95% ci, 0.56-0.91;P < 0.01)。上尿路亚组无明显的DFS改善(P = 0.28) (P -相互作用= 0.01)。PD-L1状态(p-相互作用= 0.83)和以前的新辅助化疗(p-相互作用= 0.11)对结果没有显著影响。然而,免疫治疗与更高级别≥3 ae相关(RR 1.47;P < 0.01), OS差异无统计学意义(P = 0.07)。结论:与PD-L1状态无关,佐剂PD-1/PD-L1抑制剂可显著增强MIUC DFS,尤其是下道肿瘤。这些发现支持免疫治疗,特别是抗pd1,作为高风险MIUC患者的一种有价值的辅助治疗策略。
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引用次数: 0
A French Multicenter Real-Life Study on the Biological and Clinical Parameters Associated With Response to Immune Checkpoint Inhibitors (ICIs) in Second-Line Treatment of Advanced Urothelial Carcinoma: Impact of Antibiotics Administration at the Time of ICIs Initiation 一项法国多中心现实生活研究:在晚期尿路上皮癌二线治疗中,与免疫检查点抑制剂(ICIs)反应相关的生物学和临床参数:ICIs开始时抗生素给药的影响。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.clgc.2024.102283
Pierre Grassi , Werner Hilgers , Romain Boissier , Alexandre Bertucci , Damien Bruyat , Florence Duffaud , Faustine Enoch , Philippe Rochigneux , Julien Mancini , Jean-Laurent Deville

Background

After failure of first-line chemotherapy, standard of care for advanced urothelial cancer (aUC) is immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 pathway. Several prognostic models (Bajorin and Bellmunt scores) have been evaluated, but only in the context of chemotherapy.

Objective

To study whether the variables in these scores and new emerging clinical and biological criteria have an impact on the probability of objective response in aUC treated with ICIs in 2nd-line setting and beyond.

Materials and methods

Between October 2016 and March 2023, we included 168 patients treated with ICIs in 2nd-line setting or more in 2 French centers. Variables of interest were selected after a literature review and collected retrospectively. Analyses used log-rank test and multivariate models (binary logistic and Cox regressions).

Results and limitations

Median age at diagnosis was 68 years. Patients presented with bladder tumors in 73.8% and upper urinary tract tumors in 26.2%. 63.7% of patients had received only one line of chemotherapy before ICIs. Median follow-up after starting ICIs was 8.9 months.
The variables statistically associated with objective response were:
− The presence of locally advanced or lymph node-only disease compared with visceral involvement (adjusted Odds Ratio 0.19, 95% confidence interval [0.06-0.55], P = .002) and bone-only involvement (aOR 0.22 [0.08-0.64], P = .005)
− The absence of antibiotic therapy the month before/after ICIs initiation (aOR 0.31 [0.12-0.84], P = .021).
Limitations included retrospective design and small number of patients included.

Conclusion

This real-life study from 2 French centers found a higher likelihood of objective response:
− In the absence of antibiotic therapy at ICIs initiation:
− In locally advanced or lymph node-only disease, in contrast to visceral or bone-only disease.
Our results suggest that negative impact of antibiotic therapy on the response to ICIs needs to be further investigated to optimize the management of these patients.
背景:在一线化疗失败后,晚期尿路上皮癌(aUC)的标准治疗是靶向PD-1/PD-L1途径的免疫检查点抑制剂(ICIs)。一些预后模型(Bajorin和bellmont评分)已被评估,但仅在化疗的背景下。目的:研究这些评分中的变量以及新出现的临床和生物学标准是否对ii线及以上ICIs治疗aUC的客观缓解概率有影响。材料和方法:在2016年10月至2023年3月期间,我们纳入了2个法国中心的168例二线或二线以上接受ICIs治疗的患者。在文献回顾和回顾性收集后选择感兴趣的变量。分析采用log-rank检验和多变量模型(二元逻辑和Cox回归)。结果和局限性:诊断时的中位年龄为68岁。膀胱肿瘤占73.8%,上尿路肿瘤占26.2%。63.7%的患者仅接受过一次化疗。开始使用ICIs后的中位随访时间为8.9个月。与客观反应相关的统计变量为:与内脏受累相比,存在局部晚期或仅淋巴结疾病(调整优势比为0.19,95%可信区间[0.06-0.55],P = 0.002)和仅骨骼受累(aOR为0.22 [0.08-0.64],P = 0.005)——在ICIs开始前/后一个月没有抗生素治疗(aOR为0.31 [0.12-0.84],P = 0.021)。局限性包括回顾性设计和纳入的患者数量较少。结论:这项来自法国2个中心的现实研究发现,与内脏或骨骼疾病相比,在ICIs开始时没有抗生素治疗的情况下,在局部晚期或淋巴结疾病中,客观反应的可能性更高。我们的研究结果表明,抗生素治疗对ICIs反应的负面影响需要进一步研究,以优化这些患者的管理。
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引用次数: 0
Activity of Platinum Chemotherapy in Men With Prostate Cancer With and Without DNA Damage Repair Mutations 铂类化疗在伴或不伴DNA损伤修复突变的前列腺癌患者中的活性
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.clgc.2024.102293
Stephanie Lakritz , Andrew Nicklawsky , Vida Alami , Manish Kohli , Chris Moskaluk , Greg Riedlinger , Bodour Salhia , Eric A. Singer , Abdul Rafeh Naqash , Ken Nepple , Stephen Edge , Zin Myint , Jill Kolesar , Nabil Adra , Thomas Flaig , Laura S. Graham

Introduction

Alterations in homologous recombination repair (HRR) genes occur in 20%-30% of men with metastatic castration-resistant prostate cancer (mCRPC) which may increase sensitivity to platinum chemotherapy. Specifically, exceptional responses to platinum chemotherapy have been reported among patients with BRCA mutations. This study aimed to evaluate the efficacy of platinum chemotherapy in patients with mCRPC with and without HRR.

Patient and Methods

In this retrospective, multi-institution series, we analyzed patients with mCRPC to assess response to platinum-containing chemotherapy based on HRR alteration status. Outcome measures were prostate specific antigen (PSA)50 response rate (percentage of patients achieving at least a 50% decline in PSA from baseline), overall survival (OS) and progression-free survival (PFS).

Results

From 1999 to 2020, 24 patients with mCRPC who received platinum chemotherapy were included with 7 patients analyzable for PSA outcomes. HRR alterations were found in 19 out of 24 patients (79.2%) with mutations recognized in 11 different HRR genes. Patients with a HRR alteration achieved a PSA50 response rate of 20% (1 out of 5) after platinum chemotherapy compared to 50% (1 out of 2) in patients without a HRR mutation. No difference in OS or PSA PFS was detected among patients with BRCA1/2 mutations compared to HRR alterations other than BRCA1/2 and patients without HRR alterations.

Conclusion

In patients with mCRPC, we did not find a statistical difference in anti-tumor activity after receiving platinum chemotherapy among patients harboring a pathogenic HRR alterations compared to patients without a HRR alteration. Additionally, we were unable to detect an association between BRCA1/2 mutation status and response to platinum chemotherapy. Platinum chemotherapy, however, had clinically meaningful activity in a subset of patients regardless of HRR alteration status. Additional studies are warranted using genomic data to predict sensitivity to platinum chemotherapy.
同源重组修复(HRR)基因的改变发生在20%-30%的转移性去势抵抗性前列腺癌(mCRPC)患者中,这可能会增加对铂化疗的敏感性。具体来说,BRCA突变患者对铂类化疗的特殊反应已被报道。本研究旨在评价铂化疗在伴有和不伴有HRR的mCRPC患者中的疗效。患者和方法:在这个多机构的回顾性系列研究中,我们分析了mCRPC患者,根据HRR改变状态评估其对含铂化疗的反应。结果测量是前列腺特异性抗原(PSA)50缓解率(PSA从基线至少下降50%的患者百分比),总生存期(OS)和无进展生存期(PFS)。结果:从1999年到2020年,24例mCRPC患者接受铂化疗,其中7例可分析PSA结果。24例患者中有19例(79.2%)的HRR发生改变,11种不同的HRR基因发生突变。HRR突变的患者在铂化疗后的PSA50缓解率为20%(1 / 5),而无HRR突变的患者为50%(1 / 2)。BRCA1/2突变患者与非BRCA1/2 HRR改变患者和无HRR改变患者相比,OS或PSA PFS无差异。结论:在mCRPC患者中,我们没有发现具有致病性HRR改变的患者与没有HRR改变的患者在接受铂类化疗后的抗肿瘤活性有统计学差异。此外,我们无法检测BRCA1/2突变状态与铂类化疗反应之间的关联。然而,无论HRR改变状态如何,铂类化疗在一部分患者中具有临床意义的活性。进一步的研究需要使用基因组数据来预测对铂类化疗的敏感性。
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引用次数: 0
A Prospective Non-interventional Real-World Study of cabozantinib in Pretreated Patients With Advanced Renal Cell Carcinoma Refractory to Vascular Endothelial Growth Factor-Targeted Therapy (CASSIOPE) 卡博替尼在血管内皮生长因子靶向治疗(CASSIOPE)难治性晚期肾癌患者中的前瞻性非介入性现实世界研究
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.clgc.2024.102285
Michael Staehler , Umberto Basso , Jean-Christophe Eymard , Philippe Barthelemy , Pierre Bigot , Mathieu Laramas , Michael Rink , Cristina Suarez , Aline Guillot , Jens Bedke , Paul Hamberg , Rocco De Vivo , Pablo Gajate , Martín Lázaro-Quintela , Priti Rastogi , Valérie Perrot , Bryan Qvick , Pascale Dutailly , Elena Verzoni , Giuseppe Procopio

Background

There is a lack of published data on real-world cabozantinib use in patients with advanced renal cell carcinoma after prior vascular endothelial growth factor (VEGF)-targeted therapy.

Methods

CASSIOPE was a real-world, prospective, multicenter, non-interventional postauthorization safety study of cabozantinib in adult patients with advanced renal cell carcinoma in Europe following prior VEGF-targeted treatment (NCT03419572). Endpoints included cabozantinib utilization (dose modifications due to adverse events [AEs; primary endpoint], dose, dose modifications, and treatment duration), safety, effectiveness (progression-free survival [PFS], overall survival [OS], best overall response [BOR]), and healthcare resource utilization.

Findings

Full analysis set (FAS)/safety population comprised 679 patients; 433 of these initiated cabozantinib at 60 mg/day (recommended dose) (primary safety population). Median age (FAS) was 67 (range, 29-93) years; most were male (73·0%), had clear-cell histology (85·7%), metastatic disease at cabozantinib initiation (97·8%), and prior nephrectomy (80·3%). In the primary safety population, 77·1% experienced dose modification owing to an AE. In the safety population, the median daily dose was 40·0 (range, 7·8-60·0) mg/day and the median treatment duration was 7·8 (< 0·1-15·2) months. Treatment-emergent and treatment-related AEs were experienced by 95·9% and 90·4% of patients, respectively. Median PFS (FAS) assessed by the local investigator using any method was 8·3 months, and 1-year OS rate was 74%. Approximately one-third of all patients had a BOR of partial response and 6 had a complete response.

Interpretation

Second- or later-line cabozantinib was effective and manageable in a real-world setting and had a safety profile consistent with previous studies.
背景:目前还缺乏关于卡博赞替尼在晚期肾细胞癌患者既往血管内皮生长因子(VEGF)靶向治疗后的实际使用数据。CASSIOPE是一项真实世界的、前瞻性的、多中心的、非介入的授权后安全性研究,在欧洲,卡博赞替尼用于接受vegf靶向治疗的成年晚期肾细胞癌患者(NCT03419572)。终点包括卡博赞替尼的使用(由于不良事件引起的剂量变化[ae;主要终点]、剂量、剂量调整和治疗持续时间)、安全性、有效性(无进展生存期[PFS]、总生存期[OS]、最佳总缓解期[BOR])和医疗资源利用率。结果:全分析集(FAS)/安全人群共679例;其中433例起始剂量为60 mg/天(推荐剂量)的卡博赞替尼(主要安全人群)。中位年龄(FAS) 67岁(范围29 ~ 93岁);大多数为男性(73.3%),有透明细胞组织学(85.7%),卡博替尼起始时有转移性疾病(97.8%),既往有肾切除术(83%)。在主要安全人群中,77.1 %的人因AE而经历剂量调整。在安全人群中,中位日剂量为40.0(范围为7.8 ~ 600)mg/天,中位治疗持续时间为7.8(< 0.01 ~ 15.2)个月。治疗紧急事件发生率为95.9%,治疗相关事件发生率为90.9%。当地调查员采用任何方法评估的中位PFS (FAS)为8.3个月,1年OS率为74%。大约三分之一的患者有部分缓解的BOR, 6例有完全缓解。解释:二线或二线cabozantinib在现实环境中是有效和可控的,其安全性与先前的研究一致。
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引用次数: 0
Robot-Assisted Cystectomy in Patients With Previous Pelvic Irradiation: A Comprehensive Systematic Review and Single-Arm Meta-Analysis 机器人辅助膀胱切除术在既往盆腔放疗患者中的应用:一项综合系统评价和单臂荟萃分析。
IF 2.3 3区 医学 Q3 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.clgc.2024.102259
Richard Dobrucki de Lima , Lucas Schenk de Almeida , Eduardo Lopes Martins Filho , José Maurício Mota , Leopoldo Alves Ribeiro-Filho , Caio Vinicius Suartz
To evaluate the perioperative outcomes of robot-assisted cystectomy in previous pelvic irradiation patients. We performed a systematic review with a single-arm meta-analysis, searching the PubMed, Embase, Scopus, and Cochrane databases through July 2024. Included studies reported perioperative outcomes of robot-assisted radical cystectomy in patients with prior pelvic irradiation. Extracted data included operative time, blood loss, complication rates (using the Clavien-Dindo classification), readmission rates, and length of hospital stay. Study quality was assessed and a single-arm meta-analysis was conducted to synthesize the data. This systematic review included 150 patients from 4 retrospective studies. The median operative time ranged from 330 to 382 minutes (Overall Mean = 349.50 min; 95% CI, 331-380), and blood loss varied between 264 mL and 495 mL (Overall Mean = 351.50 mL; 95% CI, 264-495). Major complications, defined as Clavien-Dindo grade ≥ III, were reported in 20% to 32% of cases, while total early complications within 90 days ranged from 53% to 59% (Overall rate = 0.58; 95% CI, 0.42-0.75). The readmission rate within 90 days varied between 22% and 40% (Overall rate = 0.31; 95% CI, 0.16-0.47). RARC in patients with prior pelvic irradiation resulted in comparable perioperative outcomes to nonirradiated patients. This review highlights the potential safety and efficacy of RARC in this complex patient group. Future studies comparing surgical approaches with detailed reporting on radiation exposure are essential to validate these findings.
目的:评价机器人辅助膀胱切除术对既往盆腔放疗患者围手术期疗效。我们通过单臂荟萃分析进行了系统评价,检索了PubMed、Embase、Scopus和Cochrane数据库,检索截止到2024年7月。纳入的研究报告了机器人辅助根治性膀胱切除术对既往盆腔照射患者的围手术期预后。提取的数据包括手术时间、出血量、并发症发生率(使用Clavien-Dindo分类)、再入院率和住院时间。对研究质量进行评估,并进行单臂荟萃分析以综合数据。本系统综述包括来自4项回顾性研究的150例患者。中位手术时间330 ~ 382分钟(总平均349.50分钟;95% CI, 331-380),失血量在264 mL和495 mL之间变化(总体平均值= 351.50 mL;95% ci, 264-495)。主要并发症(定义为Clavien-Dindo分级≥III)发生率为20% ~ 32%,而90天内早期并发症总数为53% ~ 59%(总发生率= 0.58;95% ci, 0.42-0.75)。90天内的再入院率在22%到40%之间变化(总体率= 0.31;95% ci, 0.16-0.47)。盆腔放疗患者的RARC围手术期预后与未放疗患者相当。本综述强调了RARC在这一复杂患者群体中的潜在安全性和有效性。未来的研究比较手术入路与辐射暴露的详细报告是验证这些发现的必要条件。
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引用次数: 0
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Clinical genitourinary cancer
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