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Should Only Patients with BRCA Mutation Be Treated with a Combination of an Androgen Receptor Pathway Inhibitor and a PARP Inhibitor for Metastatic Castration-resistant Prostate Cancer? The Answer Is No. 只有 BRCA 基因突变的患者才应该接受雄激素受体通路抑制剂和 PARP 抑制剂联合治疗转移性阉割耐药前列腺癌吗?答案是否定的。
IF 4.8 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-17 DOI: 10.1016/j.euf.2024.07.015
Fred Saad

Patients who benefit the most from combinations of an androgen receptor pathway inhibitor and a PARP inhibitor are those with a BRCA mutation, but there are certainly patients without BRCA mutations who will benefit from this treatment strategy.

从雄激素受体通路抑制剂和 PARP 抑制剂联合治疗中获益最多的患者是那些 BRCA 基因突变的患者,但当然也有一些没有 BRCA 基因突变的患者会从这种治疗策略中获益。
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引用次数: 0
Testicular Germ Cell Tumors with Venous Tumor Thrombus: Prevalence, Presentation, and Management. 伴有静脉瘤栓的睾丸生殖细胞瘤:发病率、表现和处理。
IF 4.8 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-14 DOI: 10.1016/j.euf.2024.07.017
Sophia Y Chahine, Khalid Y Alkhatib, Gevorg Arakelyan, Claire Buxton, Gianluca Giannarini, Robert J Hamilton, Sarah K Holt, Jean-Christophe Bernhard, Di Maria Jiang, Daniel Lin, Jen-Jane Liu, Brandon Manley, Viraj A Master, Vsevolod Matveev, Andrea Necchi, Vignesh T Packiam, Sunil H Patel, Taylor Peak, Charles C Peyton, Phillip M Pierorazio, Gagan Prakash, Keyan Salari, Wade J Sexton, Nirmish Singla, Philippe E Spiess, Sarah P Psutka

Background and objective: There are limited data on the prevalence and management of testicular germ cell tumor (TGCT) cases presenting with venous tumor thrombus (VTT). Our objectives were to describe the prevalence of TGCT with VTT, to identify a multicenter retrospective cohort, and to ascertain expert opinion regarding optimal management of this entity.

Methods: Using the IBM Marketscan database, we identified men with testicular cancer who underwent retroperitoneal lymph node dissection (RPLND) with concurrent VTT or inferior vena cava (IVC) tumor thrombectomy to estimate the prevalence of VTT in TGCT. To identify a multicenter retrospective cohort of patients, we surveyed surgeons and described the presentation, management, and outcomes for the cohort.

Key findings and limitations: The prevalence of TGCT with VTT in the IBM Marketscan database was 0.3% (n = 7/2517) when using stringent criteria and 3.1% (n = 79/2517) when using broad criteria. In response to our survey, 16 surgeons from ten centers contributed data for 34 patients. Most patients (n = 29, 85%) presented with nonseminomatous germ cell tumor. Surgical management was used for 93.9% (n = 31), including postchemotherapy tumor thrombectomy with primary cavorrhaphy in 63%. The Marketscan analysis was limited to insured individuals and did not include clinicopathological details, and use of billing codes may have included patients with stromal tumors. In addition, lack of responses to the anonymous survey limited data capture, and the RedCap survey did not address symptoms specific to IVC obstruction or allow central review of the imaging leading to VTT diagnosis.

Conclusions and clinical implications: VTT among males with TGCT is rare and requires complex multidisciplinary management, including venous tumor thrombectomy at the time of postchemotherapy RPLND.

Patient summary: Using a medical database, we estimated that the frequency of testicular cancer cases in which the tumor extends into a blood vessel (called venous tumor thrombus, VTT) is just 0.3-3.1%. We carried out a survey of surgeons with experience of this condition. Our results indicate that although testicular cancers respond well to chemotherapy, VTT is less responsive and complex surgery is necessary for this rare condition.

背景和目的:关于伴有静脉瘤栓(VTT)的睾丸生殖细胞瘤(TGCT)病例的发病率和治疗方法的数据十分有限。我们的目的是描述伴有 VTT 的睾丸生殖细胞瘤的发病率,确定一个多中心回顾性队列,并就这一实体的最佳治疗方法确定专家意见:利用 IBM Marketscan 数据库,我们确定了接受腹膜后淋巴结清扫术 (RPLND) 并同时进行 VTT 或下腔静脉 (IVC) 肿瘤血栓切除术的男性睾丸癌患者,以估算 VTT 在 TGCT 中的发病率。为了确定一个多中心回顾性患者队列,我们对外科医生进行了调查,并描述了该队列的表现、管理和结果:在 IBM Marketscan 数据库中,如果采用严格标准,TGCT 伴有 VTT 的患病率为 0.3%(n = 7/2517),如果采用宽泛标准,患病率为 3.1%(n = 79/2517)。针对我们的调查,来自 10 个中心的 16 位外科医生提供了 34 位患者的数据。大多数患者(n = 29,85%)患有非肉芽肿性生殖细胞瘤。93.9%的患者(31人)接受了手术治疗,其中63%的患者接受了化疗后肿瘤血栓切除术和原发性瓣膜成形术。Marketscan 分析仅限于投保人,不包括临床病理学细节,使用的账单代码可能包含了间质瘤患者。此外,匿名调查缺乏回应也限制了数据采集,RedCap调查没有涉及IVC阻塞的特殊症状,也不允许对导致VTT诊断的影像学进行集中审查:在患有 TGCT 的男性中,VTT 比较罕见,需要进行复杂的多学科治疗,包括在化疗后 RPLND 时进行静脉肿瘤血栓切除术。患者摘要:我们利用医疗数据库估计,肿瘤延伸至血管(称为静脉肿瘤血栓,VTT)的睾丸癌病例发生率仅为 0.3-3.1%。我们对对此有经验的外科医生进行了调查。我们的调查结果表明,虽然睾丸癌对化疗反应良好,但 VTT 的反应较差,这种罕见情况需要进行复杂的手术。
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引用次数: 0
New Drugs for Targeted Radionuclide Therapy in Metastatic Prostate Cancer. 用于转移性前列腺癌放射性核素靶向治疗的新药。
IF 4.8 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-13 DOI: 10.1016/j.euf.2024.07.016
Kévin Hébert, Paul Bodin-Cufi, Cyril Fersing, Emmanuel Deshayes

Metastatic prostate cancer is a frequent and fatal disease. Targeted radionuclide therapy (TRT) has become a readily available therapeutic option since the approval of [177Lu]Lu-PSMA-617. Various molecules are currently being studied for TRT in prostate cancer. We review various combinations of isotopes and vectors being used to target prostate cancer cells and optimize pharmacokinetics. Promising innovations include chemical modifications to improve biodistribution, identification of new targets, and the use of novel radioisotopes such as α emitters. PATIENT SUMMARY: Our mini review summarizes research on targeted radioactive drugs for treatment of metastatic prostate cancer. Several promising radioactive pharmaceuticals are being evaluated in clinical trials, but more studies are necessary before these can be used in routine clinical practice.

转移性前列腺癌是一种常见的致命疾病。自[177Lu]Lu-PSMA-617获批以来,靶向放射性核素治疗(TRT)已成为一种现成的治疗方法。目前正在研究用于前列腺癌 TRT 的各种分子。我们回顾了用于靶向前列腺癌细胞和优化药代动力学的同位素和载体的各种组合。有前景的创新包括改善生物分布的化学修饰、新靶点的确定以及新型放射性同位素(如α发射体)的使用。患者摘要:我们的微型综述总结了治疗转移性前列腺癌的靶向放射性药物研究。目前正在对几种前景看好的放射性药物进行临床试验评估,但在将这些药物用于常规临床实践之前,还需要进行更多的研究。
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引用次数: 0
Systemic Treatments for Metastatic Prostate Cancer in 2024. 2024 年转移性前列腺癌的系统治疗。
IF 4.8 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-09 DOI: 10.1016/j.euf.2024.07.013
Marco Gizzi, Emmanuel Seront, Bertrand Tombal, Julien Van Damme

Advanced metastatic prostate cancer is a heterogeneous disease for which androgen deprivation therapy combined with and androgen receptor pathway inhibitor (ARPI) is the mainstay of treatment. All available therapies may be used in sequence after the ARPI. However, patient selection is key. There is a need to identify clinical or molecular predictive factors to assist in selecting systemic treatment sequences.

晚期转移性前列腺癌是一种异质性疾病,雄激素剥夺疗法联合雄激素受体通路抑制剂(ARPI)是其主要治疗手段。在使用 ARPI 后,可依次使用所有可用的疗法。然而,患者的选择是关键。有必要确定临床或分子预测因素,以帮助选择系统治疗顺序。
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引用次数: 0
External Validation of Stockholm3 in a Retrospective German Clinical Cohort. 在一个回顾性德国临床队列中对斯德哥尔摩 3 指数进行外部验证。
IF 4.8 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-06 DOI: 10.1016/j.euf.2024.07.009
Derya Tilki, Niclas Rejek, Florian Nohe, Alexander Haese, Markus Graefen, Imke Thederan

Background and objective: Stockholm3 is a comprehensive blood test amalgamating protein biomarkers, genetic indicators, and clinical data to predict clinically significant prostate cancer risk (International Society of Urological Pathology grade ≥2 upon biopsy). Our study aims to externally validate Stockholm3 and compare its performance with the use of prostate-specific antigen (PSA) and the Rotterdam Prostate Cancer Risk Calculator (RPCRC) for clinically significant prostate cancer detection.

Methods: We gathered data from men subjected to prostate biopsies at the Martini-Klinik, Germany, between 2014 and 2017. Participants were selected based on elevated PSA levels or suspicious digital rectal examinations, all undergoing a 10-12-core systematic biopsy without a magnetic resonance imaging-targeted biopsy. We assessed Stockholm3 and RPCRC performance for clinically significant prostate cancer detection. Furthermore, we compared the proportion of men recommended for biopsy and biopsy outcomes with Stockholm3 and RPCRC against PSA ≥3 ng/ml.

Key findings and limitations: Our study encompassed 405 biopsied men, with a median age of 66 yr (interquartile range [IQR]: 60-72), PSA levels at 7 ng/ml (IQR: 5.2-10.8), and Stockholm3 scores at 18 (IQR: 10-34). Among them, 128 men (31%) received clinically significant prostate cancer diagnoses. Employing the recommended Stockholm3 threshold (≥15) could have reduced unnecessary biopsies by 52%, while detecting 92% of clinically significant cases compared with using PSA ≥3 ng/ml as a biopsy criterion. Both Stockholm3 and RPCRC exhibited strong discrimination, with area under the curve values of 0.80 (95% confidence interval [CI]: 0.76-0.85) and 0.75 (95% CI: 0.70-0.80), respectively. Stockholm3 demonstrated good calibration, while RPCRC underestimated the risk compared with observed outcomes. Moreover, Stockholm3 yielded positive clinical net benefits, whereas RPCRC yielded negative net benefits for clinically relevant thresholds.

Conclusions and clinical implications: Stockholm3 utilization could detect 92% of clinically significant prostate cancer cases while simultaneously reducing unnecessary biopsies by 52%, compared with the PSA ≥3 ng/ml criterion, based on our analysis within a cohort of men who underwent systematic biopsies.

Patient summary: In a German clinical cohort of 405 men, Stockholm3, a blood test for early prostate cancer detection, exhibited favorable clinical benefits. It identified a substantial number of clinically significant cases while reducing unnecessary biopsies by over half in men without the disease and those with clinically nonsignificant prostate cancer.

背景和目的:Stockholm3是一种综合血液检测方法,融合了蛋白质生物标记物、遗传指标和临床数据,可预测具有临床意义的前列腺癌风险(国际泌尿病理学会活检分级≥2)。我们的研究旨在对斯德哥尔摩3进行外部验证,并将其性能与使用前列腺特异性抗原(PSA)和鹿特丹前列腺癌风险计算器(RPCRC)进行临床重大前列腺癌检测进行比较:我们收集了2014年至2017年期间在德国马蒂尼医院接受前列腺活检的男性数据。参与者是根据 PSA 水平升高或可疑的数字直肠检查结果选出的,他们都接受了 10-12 核心的系统性活检,但没有进行磁共振成像靶向活检。我们评估了斯德哥尔摩3和RPCRC在临床重大前列腺癌检测方面的性能。此外,我们还比较了针对PSA≥3 ng/ml推荐进行活检的男性比例以及Stockholm3和RPCRC的活检结果:我们的研究涵盖了 405 名活检男性,他们的中位年龄为 66 岁(四分位间距 [IQR]:60-72),PSA 水平为 7 ng/ml(IQR:5.2-10.8),Stockholm3 评分为 18(IQR:10-34)。其中,128 名男性(31%)被确诊为具有临床意义的前列腺癌。与使用 PSA≥3 纳克/毫升作为活检标准相比,采用推荐的斯德哥尔摩 3 临界值(≥15)可将不必要的活检减少 52%,同时检测出 92% 有临床意义的病例。Stockholm3和RPCRC都具有很强的区分度,曲线下面积值分别为0.80(95%置信区间[CI]:0.76-0.85)和0.75(95%置信区间:0.70-0.80)。与观察结果相比,Stockholm3 显示出良好的校准性,而 RPCRC 则低估了风险。此外,Stockholm3 的临床净效益为正,而 RPCRC 的临床相关阈值净效益为负:患者总结:在德国一个由 405 名男性组成的临床队列中,用于早期前列腺癌检测的血液检测方法 Stockholm3 显示出了良好的临床效益。它发现了大量有临床意义的病例,同时将未患前列腺癌和无临床意义前列腺癌的男性不必要的活检次数减少了一半以上。
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引用次数: 0
Update on APPEAL, an International Randomized Controlled Trial Evaluating Ciprofloxacin Versus Placebo in Patients Undergoing Shockwave Lithotripsy for Urolithiasis. 评估环丙沙星与安慰剂在接受冲击波碎石术治疗尿路结石患者中应用情况的国际随机对照试验 APPEAL 的最新进展。
IF 4.8 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-06 DOI: 10.1016/j.euf.2024.07.011
Kari A O Tikkinen, Sara V Tornberg, Jani Ruotsalainen, Borna Tadayon Najafabadi, Saana Horstia, Sakineh Hajebrahimi, Arto Mikkola, Mohamed Abdelkareem, Patrick O Richard, Kathrin Bausch, Sameer Parpia, Gordon H Guyatt, Philippe D Violette

The blinded APPEAL trial is assessing the effectiveness of antimicrobial prophylaxis in preventing infections after shockwave lithotripsy for urinary stones. This large, pragmatic, international trial will provide trustworthy evidence to inform guidelines and influence global practices.

APPEAL 盲法试验正在评估抗菌药预防措施在预防泌尿系结石冲击波碎石术后感染方面的效果。这项大型、务实的国际试验将提供可信赖的证据,为指导原则提供依据,并影响全球实践。
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引用次数: 0
Novel Antibiotics for Urinary Tract Infection (UTI): The EAGLE 2 and EAGLE-3 Trials for Uncomplicated UTI, and the CERTAIN-1 Trial for Complicated UTI. 治疗尿路感染 (UTI) 的新型抗生素:针对非复杂性 UTI 的 EAGLE 2 和 EAGLE-3 试验,以及针对复杂性 UTI 的 CERTAIN-1 试验。
IF 4.8 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-06 DOI: 10.1016/j.euf.2024.07.014
Florian Wagenlehner

Two novel antibiotics have been evaluated for the treatment of urinary tract infection (UTI). Gepotidacin was an efficacious first-in-class oral antibiotic in uncomplicated UTI in comparison to nitrofurantoin. Cefepime/taniborbactam was superior to meropenem in complicated UTI and acute pyelonephritis.

对治疗尿路感染(UTI)的两种新型抗生素进行了评估。与硝基呋喃妥因相比,开博他星是治疗无并发症UTI的第一种有效口服抗生素。在复杂性UTI和急性肾盂肾炎中,头孢吡肟/他尼巴坦优于美罗培南。
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引用次数: 0
Targeting Androgen Receptor Alterations in Metastatic Prostate Cancer. 针对转移性前列腺癌中的雄激素受体改变。
IF 4.8 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-05 DOI: 10.1016/j.euf.2024.07.012
Pawel Rajwa, Piotr Zapała, Axel S Merseburger

There have been significant advances in our understanding of the biology of metastatic prostate cancer (mPCa) and its response to therapy. Androgen receptor (AR) alterations, including mutations, amplifications, splice variants, and alternative activations, play a significant role in mPCa resistance to treatment. Recent studies indicate that AR alterations detected via genomic testing can be considered predictive biomarkers in men with castration-resistant PCa and can guide treatment strategies. Novel therapeutic approaches, including AR antagonists and inhibitors of ACK1, the AR N-terminal domain, or cytochrome P450 11A1, have shown promise in overcoming treatment resistance. Ongoing clinical trials are exploring the efficacy of these treatments in relation to AR mutation status and could potentially transform the treatment landscape for mPCa. PATIENT SUMMARY: Our mini review highlights advances in the treatment of metastatic prostate cancer, with a focus on drugs that target genetic alterations affecting a protein called the androgen receptor. Some promising results have been obtained and clinical trials are ongoing.

我们对转移性前列腺癌(mPCa)的生物学特性及其治疗反应的了解取得了重大进展。雄激素受体(AR)的改变,包括突变、扩增、剪接变异和替代活化,在前列腺癌的耐药性中起着重要作用。最近的研究表明,通过基因组检测发现的AR改变可被视为男性阉割耐药PCa患者的预测性生物标志物,并可指导治疗策略。新的治疗方法,包括AR拮抗剂和ACK1、AR N-末端结构域或细胞色素P450 11A1的抑制剂,已显示出克服耐药性的希望。目前正在进行的临床试验正在探索这些治疗方法的疗效与AR突变状态的关系,并有可能改变mPCa的治疗格局。患者摘要:我们的微型综述重点介绍了转移性前列腺癌的治疗进展,重点是针对影响雄激素受体蛋白基因改变的药物。目前已经取得了一些有希望的结果,临床试验正在进行中。
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引用次数: 0
Macroplastique Is a Safe and Effective Long-term Surgical Treatment for Stress Urinary Incontinence: Prospective Study with 10-Year Follow-up. Macroplastique 是一种安全有效的压力性尿失禁长期手术治疗方法:10年随访的前瞻性研究。
IF 4.8 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-08-02 DOI: 10.1016/j.euf.2024.07.010
Maurizio Serati, Chiara Scancarello, Giada Mesiano, Chiara Cimmino, Maria Rosaria Campitiello, Stefano Salvatore, Fabio Ghezzi, Giorgio Caccia, Andrea Papadia, Andrea Braga

Background and objective: Until a few years ago, a midurethral sling was considered the gold standard for the treatment of female stress urinary incontinence (SUI) after failure of conservative therapies. However, criticisms regarding the rate of mesh exposure and lack of long-term efficacy have led to reconsideration of other surgical procedures. Our aim was to investigate long-term subjective and objective outcomes after injection of Macroplastique, a urethral bulking agent.

Methods: We prospectively enrolled all consecutive women complaining of pure SUI symptoms with urodynamically proven SUI who received a Macroplastique injection. We investigated patient-reported subjective outcomes using International Consultation on Incontinence Questionnaire-Short Form, Urogenital Distress Inventory, Patient Global Impression of Improvement, and Visual Analog Scale (VAS) questionnaires, and the cough stress test to assess objective outcomes. Adverse events were recorded during follow-up.

Key findings and limitations: At 10 yr after Macroplastique injection, the objective cure rate was 56% and 71% of patients reported that they were satisfied. Long-term data revealed no significant decline in subjective or objective cure rates. No serious complications were reported. Study limitations include the small sample size and the lack of pad tests and bladder diaries for postoperative evaluations.

Conclusions and clinical implications: Our study shows that Macroplastique injection can be an effective and safe option for the treatment of female SUI in the long term, even when used in the first-line setting.

Patient summary: We evaluated outcomes for women with stress urinary incontinence (SUI) who were treated with an injection of Macroplastique gel into the wall of the urethra to prevent leakage of urine. We found that this is a safe option for treatment of female SUI that is effective in the long term.

背景和目的:直到几年前,尿道中段吊带一直被认为是保守疗法失败后治疗女性压力性尿失禁(SUI)的金标准。然而,有关网片暴露率和缺乏长期疗效的批评导致人们重新考虑其他手术方法。我们的目的是研究注射尿道膨出剂 Macroplastique 后的长期主观和客观效果:方法:我们前瞻性地登记了所有主诉单纯 SUI 症状并经尿动力学证实 SUI 的连续女性,她们都接受了 Macroplastique 注射。我们使用国际尿失禁咨询问卷-简表、尿道窘迫量表、患者总体改善印象和视觉模拟量表(VAS)问卷调查了患者报告的主观结果,并使用咳嗽压力测试评估了客观结果。随访期间记录了不良事件:注射 Macroplastique 10 年后,客观治愈率为 56%,71% 的患者表示满意。长期数据显示,主观和客观治愈率均无明显下降。没有严重并发症的报道。研究的局限性包括样本量较小,术后评估缺乏尿垫测试和膀胱日记:患者总结:我们评估了压力性尿失禁(SUI)女性患者的治疗效果,她们在尿道壁注射 Macroplastique 凝胶以防止漏尿。我们发现,这是一种治疗女性 SUI 的安全选择,而且长期有效。
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引用次数: 0
Urinary Microbiome Research Has Not Established a Conclusive Influence: Revisiting Koch's Postulates. 泌尿系统微生物组研究尚未确立结论性影响:重温科赫假设
IF 4.8 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-07-31 DOI: 10.1016/j.euf.2024.07.005
Glenn T Werneburg, Jennifer Southgate

In order to establish a causal relationship between urinary microbiota and a urological disease or condition, a series of rigorous scientific criteria must be met. Demonstration of an association between microbiota and a condition does not necessarily imply causality, importance, or clinical relevance.

要确定尿液微生物群与泌尿系统疾病或症状之间的因果关系,必须符合一系列严格的科学标准。证明微生物群与疾病之间存在关联并不一定意味着因果关系、重要性或临床相关性。
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引用次数: 0
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European urology focus
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