Clinical genitourinary cancer最新文献_第3页

Real-World Outcomes of Enfortumab Vedotin and Pembrolizumab in Advanced Urothelial Carcinoma: A Multicenter Retrospective Analysis 对晚期尿路上皮癌患者使用维多汀和派姆单抗的实际疗效：一项多中心回顾性分析

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-10-13 DOI: 10.1016/j.clgc.2025.102453

Prateek Jain , Syed Arsalan Ahmed Naqvi , Nikita Tripathi , Japneet K Oberoi , Muhammad Abdullah Humayun , Yousef Zakharia , Jacob J Orme , Adam Kase , Dan S Childs , Ruqin Chen , Irbaz B Riaz , Parminder Singh

Introduction

Enfortumab vedotin plus pembrolizumab has emerged as a new standard of care for previously untreated patients with advanced urothelial carcinoma following the EV-302 trial. However, data on its efficacy and safety in routine clinical practice remain limited. Herein, we evaluated real-world clinical outcomes for patients with advanced urothelial carcinoma receiving the combination as first-line or subsequent-line therapy.

Patients and Methods

This retrospective cohort study included adults (≥18 years) with histologically confirmed bladder or upper tract urothelial carcinoma (other histologic type variants were also included), who initiated treatment with enfortumab vedotin-pembrolizumab therapy between May 2020 and December 2024 at the Mayo Clinic. Patients initiating therapy after December 2024 or with incomplete data were excluded. Patients were stratified by line of therapy: Cohort A included patients who received enfortumab vedotin-pembrolizumab as first-line therapy, and Cohort B included patients who received it as subsequent-line therapy. The primary endpoint was to estimate median progression-free survival in cohort A and cohort B.

Results

A total of 183 patients with advanced urothelial carcinoma treated with the enfortumab vedotin-pembrolizumab combination were included. The median age at treatment initiation was 71.9 years (IQR, 64.7-77.4). Most patients were male (71.0%) and white (90.7%). The median progression-free survival was 12.9 months (95% CI, 9.5-NE) in Cohort A and 9.3 months (95% CI, 6.3-NE) in Cohort B. This difference was not statistically significant (HR, 1.30; 95% CI, 0.83-2.04; P = .246). Treatment-related adverse events of any grade were reported in 93.4% of patients, with 30.6% experiencing Grade ≥3 AEs.

Conclusion

In this real-world cohort, enfortumab vedotin-pembrolizumab combination demonstrated meaningful clinical activity and manageable toxicity in both first-line and subsequent-line settings, consistent with results from the EV-302 trial.

在EV-302试验之后，Enfortumab vedotin + pembrolizumab已成为先前未经治疗的晚期尿路上皮癌患者的新护理标准。然而，关于其在常规临床实践中的有效性和安全性的数据仍然有限。在此，我们评估了晚期尿路上皮癌患者接受联合治疗作为一线或后续治疗的实际临床结果。患者和方法：这项回顾性队列研究纳入了组织学证实的膀胱或上尿路上皮癌（也包括其他组织学类型变异）的成年人（≥18岁），这些患者在2020年5月至2024年12月期间在梅奥诊所接受了强制维多汀-派姆单抗治疗。2024年12月以后开始治疗或资料不完整的患者被排除在外。患者按治疗线进行分层：队列A包括接受enfortumab vedotin-pembrolizumab作为一线治疗的患者，队列B包括接受该药作为后续治疗的患者。研究的主要终点是估计队列A和队列b的中位无进展生存期。结果：共有183例晚期尿路上皮癌患者接受了维多汀-派姆单抗联合治疗。开始治疗时的中位年龄为71.9岁（IQR, 64.7-77.4）。患者以男性（71.0%）和白人（90.7%）居多。队列A的中位无进展生存期为12.9个月（95% CI, 9.5-NE），队列b的中位无进展生存期为9.3个月（95% CI, 6.3-NE），差异无统计学意义（HR, 1.30; 95% CI, 0.83-2.04; P = 0.246）。93.4%的患者报告了任何级别的治疗相关不良事件，其中30.6%的患者出现≥3级ae。结论：在这个真实世界的队列中，在一线和次一线环境中，enfortumab vedotin-pembrolizumab联合用药显示出有意义的临床活性和可控的毒性，与EV-302试验的结果一致。

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引用次数: 0

Nationwide Real-World Outcomes of Trial Eligible and Trial Ineligible Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab 全国范围内符合试验条件和不符合试验条件的转移性肾细胞癌患者使用Nivolumab加Ipilimumab治疗的真实世界结果

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-10-08 DOI: 10.1016/j.clgc.2025.102450

Mette Syberg Jespersen , Jesper Andreas Evers Palshof , Niels Fristrup , Niels Viggo Jensen , Jon Røikjær Henriksen , Ane Bundsbæk Bøndergaard Iversen , Sarah Grønbech Steen , Morten Andersen , Kasper Madsen , Inge Marie Svane , Anne Kirstine Møller Darras

Introduction

Clinical trials have demonstrated efficacy and safety of immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma (mRCC). However, patients who do not meet trial eligibility criteria constitute a large proportion of the real-world population, and their outcomes remain poorly described.

Patients and Methods

This nationwide, retrospective cohort study included all Danish patients with mRCC who initiated nivolumab plus ipilimumab (NIVO/IPI) by May 5, 2022. Clinical data were obtained from electronic patient records. Outcomes included median progression-free survival (mPFS), median overall survival (mOS), and objective response rate (ORR), assessed by treating physicians. Patients were classified as trial-eligible or ineligible according to CheckMate 214 (CM214) key criteria. Survival was estimated using Kaplan–Meier methods, and subgroups were explored.

Results

A total of 464 patients were included, with a median follow-up of 33 months. In the total cohort, mPFS was 9 months, mOS 41 months, and ORR 43%, including 13% complete responses. Among 282 trial-eligible patients, outcomes were comparable to CM214 with mPFS 12 months and mOS 49 month, while 182 ineligible patients had inferior outcomes, with mPFS 6 months and mOS 26 months (both P < .001). The presence of brain metastases did not adversely affect OS, while patients with autoimmune disease demonstrated unexpectedly favorable outcomes. Severe treatment-related toxicity (≥ grade 3) occurred in 44% in the total cohort, comparable to CM214.

Conclusion

This is the first nationwide real-world study evaluating NIVO/IPI outcomes in unselected mRCC. Trial-eligible patients achieved survival outcomes comparable to clinical trial results. Although ineligible patients derived less benefit, they still experienced meaningful clinical outcomes. These findings provide benchmark data for treatment of real-world mRCC populations in routine clinical practice.

临床试验已经证明了基于免疫检查点抑制剂联合治疗转移性肾细胞癌（mRCC）的有效性和安全性。然而，不符合试验资格标准的患者占现实世界人口的很大一部分，他们的结果仍然缺乏描述。患者和方法：这项全国性的回顾性队列研究包括所有在2022年5月5日之前开始使用nivolumab + ipilimumab （NIVO/IPI）的丹麦mRCC患者。临床资料来源于电子病历。结果包括治疗医师评估的中位无进展生存期（mPFS）、中位总生存期（mOS）和客观缓解率（ORR）。根据CheckMate 214 （CM214）关键标准，将患者分为符合试验条件或不符合试验条件。使用Kaplan-Meier方法估计生存率，并对亚组进行探索。结果：共纳入464例患者，中位随访时间为33个月。在整个队列中，mPFS为9个月，mOS为41个月，ORR为43%，包括13%的完全缓解。在282例符合试验条件的患者中，mPFS 12个月和mOS 49个月的结果与CM214相当，而182例不符合试验条件的患者的结果较差，mPFS 6个月和mOS 26个月（均P < 0.001）。脑转移的存在对OS没有不利影响，而自身免疫性疾病患者表现出出乎意料的有利结果。在整个队列中，44%的患者发生了严重的治疗相关毒性（≥3级），与CM214相当。结论：这是第一个在全国范围内评估NIVO/IPI在未选择的mRCC中的结果的真实研究。符合试验条件的患者获得了与临床试验结果相当的生存结果。尽管不符合条件的患者获益较少，但他们仍然经历了有意义的临床结果。这些发现为日常临床实践中治疗真实世界mRCC人群提供了基准数据。

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引用次数: 0

Pathogenic Germline Variant Prevalence and Genetic Testing Outcomes in Patients With Urothelial Carcinoma 尿路上皮癌患者的致病种系变异患病率和基因检测结果。

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-10-08 DOI: 10.1016/j.clgc.2025.102451

Eugene Oh , Ye Chua , Piroz Bahar , Marie-Louise Accardo , Xiaochen Li , Erika Koeppe , Steven Monda , Phillip L. Palmbos , Irene Tsung , Zachery R. Reichert , Ulka N Vaishampayan , Udit Singhal , Tobias Else , Charles B. Nguyen

Introduction

Urothelial carcinoma (UC) is rarely attributed to hereditary causes, but recent studies suggest inherited factors may play a larger role. Current guidelines recommend genetic evaluation in patients with UC diagnosed at < 50 years old or features associated with Lynch syndrome. However, the full pathogenic germline variant landscape and optimal genetic evaluation criteria in UC remain poorly understood.

Patients and Methods

A retrospective analysis of all patients with UC referred for genetic evaluation between 2002 and 2024 was performed. Genetic testing outcomes, variant prevalence and characterization, and associated clinicopathologic features were recorded. Fisher’s Exact test was used to compare factors between patients with pathogenic or likely pathogenic (P/LP) variant versus those with negative testing.

Results

Overall, 128 patients underwent genetic evaluation. Median age at diagnosis was 59 (IQR: 48-68). Most (58.6%) had non-muscle invasive disease at initial diagnosis; 8.6% had metastatic disease. Pure urothelial histology was most frequent (71%). Upper tract disease was present at 14.8%. Among the cohort, 34 (26.6%) had a confirmed P/LP variant. The most common P/LP variants were Lynch syndrome-associated genes (9.4%) and DNA damage repair genes (9.4%). Having a history of ≥ 2 additional cancers was associated with a positive genetic test (P = .010). Otherwise, there were no statistically significant differences in testing outcomes based on age at diagnosis, primary tumor location, or initial stage at diagnosis.

Conclusion

Among patients with UC referred for genetic evaluation, 26.6% had a confirmed P/LP variant, although this cohort was a selected population. Age and traditional clinicopathologic features were not associated with testing results, though history of ≥ 2 additional cancers was associated. These findings may suggest a broader use of genetic evaluation in UC.

导读：尿路上皮癌（UC）很少归因于遗传原因，但最近的研究表明遗传因素可能起更大的作用。目前的指南建议对年龄小于50岁或伴有Lynch综合征的UC患者进行遗传评估。然而，UC的完整致病种系变异景观和最佳遗传评价标准仍然知之甚少。患者和方法：回顾性分析2002年至2024年间所有UC患者的遗传评估。记录基因检测结果、变异患病率和特征以及相关的临床病理特征。Fisher's Exact检验用于比较致病性或可能致病性（P/LP）变异患者与阴性检测患者之间的因素。结果：总体而言，128例患者进行了遗传评估。诊断时中位年龄为59岁（IQR: 48-68）。大多数（58.6%）在初诊时患有非肌肉侵袭性疾病；8.6%有转移性疾病。纯尿路上皮组织学最常见（71%）。上呼吸道疾病占14.8%。在该队列中，34例（26.6%）确诊为P/LP变异。最常见的P/LP变异是Lynch综合征相关基因（9.4%）和DNA损伤修复基因（9.4%）。有≥2个额外癌症病史与基因检测阳性相关（P = 0.010）。除此之外，基于诊断时的年龄、原发肿瘤位置或诊断时的初始阶段，检测结果没有统计学上的显著差异。结论：在进行遗传评估的UC患者中，26.6%的患者确认有P/LP变异，尽管该队列是一个选定的人群。年龄和传统的临床病理特征与检测结果无关，但≥2例额外癌症病史与检测结果相关。这些发现可能建议在UC中更广泛地使用遗传评估。

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引用次数: 0

Oral Toxicities of PSMA-Targeted Therapies: Mitigation Strategies and Translational Opportunities psma靶向治疗的口服毒性：缓解策略和转化机会

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-10-06 DOI: 10.1016/j.clgc.2025.102452

Chitra Priya Emperumal , Nagarajan Kannan , Daniel S. Childs , Bridget P. Keenan

Prostate-specific membrane antigen (PSMA) has gained prominence as a key target in the treatment of metastatic castration-resistant prostate cancer (mCRPC) therapy. Integrating radionuclide therapies such as Lutetium-177 [¹⁷⁷Lu]-PSMA-617 has significantly advanced treatment outcomes while posing unique challenges related to off-tumor toxicities in other tissues that express PSMA, particularly in salivary glands. Furthermore, there are novel cancer therapeutics in development including PSMA-targeted immunotherapies and antibody drug conjugates which hold promise for the treatment of prostate cancer and may contribute to the burden of oral toxicity. The oral toxicity of PSMA-targeted radioligand therapy arises from PSMA-mediated salivary gland uptake and radionuclide retention, differing fundamentally from the nonspecific tissue damage mechanisms of traditional external beam radiotherapy. In parallel, targeted therapies, including small molecules and monoclonal antibodies, exert direct effects by binding to PSMA and delivering anti-tumor metabolites and/or amplifying the immune response. The resultant off-tumor on-target tissue damage can lead to distinct oral complications such as xerostomia, dysgeusia and mucositis. Although PSMA–targeted therapies are primarily used for the management of prostate cancer, they are also being explored in treatment of salivary gland malignancies including adenoid cystic carcinoma. This review explores the mechanisms and clinical manifestations of PSMA-related oral toxicities in the context of prostate cancer, diagnosis, possible mitigation strategies, the need for preclinical models to study regulation of PSMA expression leading to oral toxicities, current challenges and future directions.

前列腺特异性膜抗原（PSMA）已成为转移性去势抵抗性前列腺癌（mCRPC）治疗的关键靶点。整合放射性核素疗法，如Lutetium-177 [177Lu]-PSMA-617，具有显著的改善治疗效果，但对其他表达PSMA的组织（特别是唾液腺）的肿瘤外毒性提出了独特的挑战。此外，一些新的癌症疗法正在开发中，包括psma靶向免疫疗法和抗体药物偶联物，它们有望治疗前列腺癌，但可能会增加口服毒性的负担。psma靶向放射配体治疗的口服毒性源于psma介导的唾液腺摄取和放射性核素保留，与传统外束放疗的非特异性组织损伤机制根本不同。与此同时，包括小分子和单克隆抗体在内的靶向治疗通过与PSMA结合并递送抗肿瘤代谢物和/或放大免疫反应来发挥直接作用。由此产生的非肿瘤靶组织损伤可导致明显的口腔并发症，如口干、发音困难和粘膜炎。虽然psma靶向治疗主要用于前列腺癌的治疗，但它们也被用于治疗包括腺样囊性癌在内的唾液腺恶性肿瘤。本文综述了前列腺癌背景下PSMA相关口服毒性的机制和临床表现、诊断、可能的缓解策略、临床前模型研究PSMA表达调控导致口服毒性的必要性、当前挑战和未来方向。

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引用次数: 0

Real-World Experience With Lenvatinib Plus Everolimus (LEN+EVE) in Patients With Pretreated Advanced Renal Cell Carcinoma (RELEVANCE): A Retrospective, Multicenter Case Series Lenvatinib +依维莫司（LEN+EVE）治疗预先治疗的晚期肾细胞癌患者的真实世界经验（相关性）：回顾性，多中心病例系列。

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-10-06 DOI: 10.1016/j.clgc.2025.102449

Hendrik Eggers , Ramona Stelmacher , Martin Bögemann , Arne Strauß , Christian Thomas , Johannes Landmesser , Stefanie Zschäbitz , Philipp Ivanyi

Introduction

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.

Patients and Methods

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.

Results

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.

Conclusions

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.

导语：转移性肾细胞癌（mRCC）预后较差，尽管最近全身治疗方案发生了变化。Lenvatinib + everolimus （LEN+EVE）是两种靶向治疗的组合，在先前的一种酪氨酸激酶抑制剂（TKI）治疗失败后被批准。我们的目的是在现实环境中评估LEN+EVE治疗mRCC患者的有效性和安全性。患者和方法：该回顾性病例系列包括2016年8月至2021年12月期间在德国6个学术中心接受LEN+EVE治疗的mRCC患者。结果包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）和安全性；全部由当地调查员评估。根据风险评分、既往治疗和初始剂量进行亚组分析。结果：81例患者被评估：中位年龄61岁（42-80岁），81.5%为男性，80.2%的患者ECOG评分为0或1。39.5%的患者在初次诊断时发现同步转移。国际转移性RCC数据库联盟（IMDC）风险状态为有利的患者占16.0%，中等的占48.1%，较差的占16.0%。LEN+EVE之前的治疗线中位数为3条（范围0-7）。LEN+EVE的中位治疗持续时间为6.1个月（0.2-29.2个月）。ORR为28.4%，DCR为61.7%，中位OS为11.3个月（95% CI, 8.7-13.9），中位PFS为6.5个月（95% CI, 5.4-7.6）。中位PFS、OS和ORR在既往接受0-2种或≥3种治疗线的患者以及既往接受或未接受免疫治疗的患者中相似。安全性是可控的，6.2%的患者因治疗相关不良事件而停止治疗。结论：LEN+EVE联合治疗在大量预先治疗的mRCC患者和具有挑战性疾病特征的现实世界队列中显示出高效率-无论治疗线，IMDC风险组，初始剂量或先前的免疫治疗。

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引用次数: 0

Analysis of Clinicopathologic Features and Imaging Findings of TFE3-Rearranged Renal Cell Carcinoma tfe3重排肾细胞癌临床病理特征及影像学表现分析。

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-10-05 DOI: 10.1016/j.clgc.2025.102446

Jianqiang Liu , Jinyan Wei , Yuting Zhang , Sitong Han , Qi Zhang , Enbo Hu , Xuejian Sun , Gang Wang , Jianhong Zhao

Objective

To examine the imaging features and clinicopathologic features of TFE3-rearranged renal cell carcinoma and highlight key imaging findings for clinical decision-making.

Methods

The imaging and clinicopathological data of 49 pathologically confirmed cases of TFE3-rearranged renal cell carcinoma from multiple institutions between January 2018 and December 2024 were retrospectively analyzed.

Results

Of the 49 patients, 17 were male and 32 were female; aged 44 ± 15 years (range: 10-82 years) , 22 were asymptomatic and 27 were symptomatic. Tumor size averaged 7.0 (range: 2.0-14.9) cm. Imaging showed 28 round-like and 21 lobulated lesions; 18 had distinct margins, while 31 had indistinct margins. A pseudocapsule was present in 36 cases, 24 of which were incomplete. Additionally, 42 tumors showed uneven density with necrosis or cystic degeneration; there were 25 cases of hemorrhage, 27 cases of irregular calcification, Peritumoral vessels were noted in 23 cases. Imaging modalities included CT (44 cases: 41 with both plain and enhanced scans, 3 with plain only), MRI (13 cases with plain and enhanced scans), and ultrasonography (15 cases, including 5 with contrast enhancement). Treatment included partial nephrectomy (21 cases), total nephrectomy (22 cases) , and biopsy (6 cases).With a median follow-up of 30 months (range: 1-72 months) until December 2024, 6 patients experienced tumor recurrence, 14 developed metastasis, and 7 died, while 5 patients were lost to follow-up.

Conclusion

TFE3-rearranged renal cell carcinoma is a rare renal tumor with distinct imaging and clinical features that can inform preoperative diagnosis, treatment, and prognosis.

目的：探讨tfe3重排肾细胞癌的影像学特征及临床病理特点，总结临床决策的关键影像学表现。方法：回顾性分析2018年1月至2024年12月间多机构49例经病理证实的tfe3重排肾细胞癌的影像学及临床病理资料。结果：49例患者中，男性17例，女性32例；年龄44±15岁（范围：10 ~ 82岁），无症状22例，有症状27例。肿瘤平均大小7.0（范围：2.0-14.9）cm，影像学示28个圆形病灶，21个分叶状病灶；18页页边明显，31页页边不明显。假包膜36例，其中24例不完整。42例肿瘤密度不均，伴坏死或囊性变性；出血25例，不规则钙化27例，瘤周血管23例。影像学方式包括CT（44例：平扫加增强41例，单纯平扫3例）、MRI（平扫加增强13例）、超声（15例，其中增强5例）。治疗包括部分肾切除术（21例）、全肾切除术（22例）和活检（6例）。截止2024年12月，中位随访30个月（1-72个月），肿瘤复发6例，转移14例，死亡7例，失访5例。结论：tfe3重排肾细胞癌是一种罕见的肾脏肿瘤，具有独特的影像学和临床特征，可指导术前诊断、治疗和预后。

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引用次数: 0

Macrophage Cell and Diagnostic Biomarkers in BLCA: Integrating Machine Learning With Single-Cell Analysis 巨噬细胞和诊断生物标志物在BLCA：整合机器学习与单细胞分析。

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-10-04 DOI: 10.1016/j.clgc.2025.102447

Guangliang Che, Xuejun Zhao, Rongtuan Luo, Quanfeng Yu, Xiaofeng Guo, Ke Gao, Kangyu Chen, Erfeng Zhang

Introduction

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.

Patients and Methods

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.

Results

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.

Conclusions

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.

膀胱癌（BLCA）预后不良，一直是临床医生面临的重大挑战。先前的研究已经证实了BLCA与巨噬细胞的密切关系。然而，巨噬细胞在BLCA中的关键亚群和分子功能尚未被揭示。利用单细胞测序技术探索巨噬细胞异质性和鉴定新的生物标志物成为可能。患者和方法：使用从Gene Expression Omnibus （GEO）获得的PBMC、BLCA和尿路上皮来源细胞（UDCs）的单细胞测序数据进行单细胞分析、伪时间分析和细胞间通讯分析。采用hdWGCNA进行无标度网络分析，选择特征基因。基于TCGA_BLCA数据进行LASSO回归和随机森林分析。建立预后模型，然后使用Gene Expression Omnibus （GEO）数据集对其进行验证。此外，使用CIBERSORT、ESTIMATE算法和TIDE数据库对高危组和低危组进行免疫浸润分析。结果：通过单细胞分析鉴定出9种巨噬细胞亚型。通过hdWGCNA鉴定了571个巨噬细胞相关基因。结合LASSO回归和RF分析，筛选出MYO5A、KCNK6、DNAJB4、DEDD2、NFKBID、PSMB10、ITPRID2等7个关键基因。基于这些基因构建了预后模型。高风险组的总生存期（OS）明显较差。模型的预测精度在一个独立的群体中得到验证。免疫分析显示，高危人群的免疫逃避增强，可能促进肿瘤进展并增加BLCA细胞的转移能力。结论：基于7个巨噬细胞相关基因构建的BLCA预后模型具有较强的预测能力。M2巨噬细胞表型在高危人群中显著富集，似乎导致肿瘤侵袭性升高。免疫浸润分析提示高危人群对免疫检查点抑制剂（ICI）治疗反应较弱。在所有已鉴定的基因中，DEDD2可能作为BLCA的预后生物标志物。

{"title":"Macrophage Cell and Diagnostic Biomarkers in BLCA: Integrating Machine Learning With Single-Cell Analysis","authors":"Guangliang Che, Xuejun Zhao, Rongtuan Luo, Quanfeng Yu, Xiaofeng Guo, Ke Gao, Kangyu Chen, 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":"2025-10-04","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}

引用次数: 0

Subcentimeter Pulmonary Nodules in Patients With Clinical Stage I Non-Seminoma: Impact on Risk and Patterns of Disease Relapse 临床I期非精原细胞瘤患者的亚厘米肺结节：对疾病复发的风险和模式的影响

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-10-02 DOI: 10.1016/j.clgc.2025.102448

Adri M. Durant , Kshitij Pandit , Nadia Islam , Mimi Nguyen , Margaret Meagher , Mai Dabbas , Lanyu Mi , Timothy D. Lyon , Fred Millard , Stephen A. Boorjian , Bradley Leibovich , Mark D. Tyson , Aditya Bagrodia

Introduction

Indeterminate subcentimeter pulmonary nodules identified during the initial staging of patients with clinical stage I non-seminoma germ cell tumor (NSGCT) remain of uncertain clinical significance and yet can increase patient anxiety and cloud management decisions. We seek to evaluate the incidence and risk of disease recurrence in stage I NSGCT patients with subcentimeter pulmonary nodules.

Methods

Patients with clinical stage I NSGCT receiving an orchiectomy from 2003 to 2024 with at least 3-months of follow-up were identified (n = 215). Patient demographics, pathologic characteristics, administration of adjuvant therapy, and disease relapse data were collected. Initial staging imaging reports were reviewed identifying patients with SPN (< 1cm). The relationship between SPN and disease recurrence was investigated.

Results

We identified 215 patients with stage I NSGCT, of whom 71 (33.0%) had SPN on initial staging imaging. A total of 52 patients (24.2%) received adjuvant treatment (primary RPLND 31 patients, primary chemotherapy 21 patients), with no significant difference in therapy between patients with and without SPN (P = .09). At a median follow-up of 22-months, disease recurrence occurred in 51 (23.7%) patients. The presence of SPN was not associated with increased risk of disease recurrence on univariate analysis (P = .12) and was associated with a decreased risk of recurrence on multivariable analysis (OR (95% CI): 0.38 (0.17, 0.83); P = .02). Of 6 patients who progressed to metastatic lung disease, only 1 patient had SPN at the time of presentation.

Conclusion

Our study suggests that SPN in stage I NSGCT are not associated with an increased risk of disease relapse. These findings may be used in patient counseling and to avoid overtreatment in management decisions.

在临床I期非精原细胞瘤生殖细胞瘤（NSGCT）患者的初始阶段发现的不确定的亚厘米肺结节仍然具有不确定的临床意义，但可能增加患者的焦虑和影响管理决策。我们试图评估伴有亚厘米肺结节的I期NSGCT患者的发病率和疾病复发风险。方法选取2003 - 2024年接受睾丸切除术的临床I期NSGCT患者（215例），随访时间至少为3个月。收集患者的人口统计学、病理特征、辅助治疗的管理和疾病复发的数据。回顾初步分期影像学报告，确定SPN （< 1cm）患者。探讨SPN与疾病复发的关系。结果215例I期NSGCT患者，其中71例（33.0%）在初始分期影像学上有SPN。共有52例（24.2%）患者接受了辅助治疗（原发性RPLND 31例，原发性化疗21例），伴有和未伴有SPN的患者治疗差异无统计学意义（P = 0.09）。在中位随访22个月时，51例（23.7%）患者出现疾病复发。单因素分析显示，SPN的存在与疾病复发风险增加无关（P = 0.12），多因素分析显示，SPN的存在与复发风险降低相关(OR (95% CI): 0.38 (0.17, 0.83)；P = .02)。在6例进展为转移性肺部疾病的患者中，只有1例患者在出现时患有SPN。结论：我们的研究表明，I期NSGCT的SPN与疾病复发风险增加无关。这些发现可用于患者咨询，并在管理决策中避免过度治疗。

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引用次数: 0

Pathological and Clinical Implications of Tumor Microenvironment Evaluated With Multiplex Immunohistochemistry in Testicular Embryonal Carcinoma 多重免疫组化评价睾丸胚胎癌肿瘤微环境的病理和临床意义。

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-10-01 DOI: 10.1016/j.clgc.2025.102444

Valentina Tateo , Costantino Ricci , Sofia Melotti , Elisa Tassinari , Matteo Rosellini , Andrea Marchetti , Linda Danielli , Antonio Maestri , Andrea Necchi , Veronica Mollica , Michelangelo Fiorentino , Francesco Massari

Introduction

Testicular germ cell tumors (TGCTs) are the most common cancer in young men. Their development is closely linked to embryogenesis, yet much about their pathogenesis remains unknown. TGCTs exhibit exceptional sensitivity to cisplatin-based chemotherapy, achieving high cure rates even in metastatic disease. Further research is needed to deepen our understanding of TGCTs and refine risk stratification. In this pilot study, we focused on embryonal carcinoma (EC), a subtype with increased risk of relapse and considered a key step in TGCT reprogramming.

Patients and Methods

We analyzed the tumor microenvironment (TME) in 49 EC samples using bright-field multiplex immunohistochemistry (BF-mIHC), which enables the simultaneous evaluation of multiple biomarkers, making it particularly useful for TME characterization. We evaluated B-cells (CD20), T-cells (CD3), and tumor-associated macrophages (TAMs, CD68) and established cutoffs that correlated with reprogramming phase, clinical stage, and relapse.

Results

High TAM levels (CD68 + > 83/mm²) were strongly associated with phase I of reprogramming (pure EC or EC mixed only with seminoma), while low TAM characterized phase II (P < .001), suggesting a role in stemness maintenance through epigenetic regulation. High CD68 (> 46/mm²) and CD3 (> 125.5/mm²) correlated with metastatic disease (P < .001 and P = .026, respectively), whereas high CD20 (> 38.5/mm²) and CD3 (> 83/mm²) were linked to lower relapse risk (P = .014 and P = .017, respectively). Important limits are small sample size and few relapse events.

Conclusions

These findings highlight the relevance of TME in TGCT biology and prognosis. The observed associations suggest TME may influence tumor plasticity, metastatization and relapse risk, warranting validation in larger studies.

睾丸生殖细胞肿瘤（tgct）是年轻男性最常见的癌症。它们的发育与胚胎发生密切相关，但其发病机制尚不清楚。tgct对以顺铂为基础的化疗表现出异常的敏感性，即使在转移性疾病中也能实现高治愈率。需要进一步的研究来加深我们对tgct的理解并完善风险分层。在这项初步研究中，我们关注胚胎癌（EC），这是一种复发风险增加的亚型，被认为是TGCT重编程的关键步骤。患者和方法：我们使用亮场多重免疫组织化学（BF-mIHC）分析了49例EC样本的肿瘤微环境（TME），该方法可以同时评估多种生物标志物，使其对TME表征特别有用。我们评估了b细胞（CD20）、t细胞（CD3）和肿瘤相关巨噬细胞（tam、CD68），并建立了与重编程阶段、临床阶段和复发相关的截止点。结果：高TAM水平（CD68 + bbb83 /mm²）与I期重编程（纯EC或EC仅与精原细胞瘤混合）密切相关，而低TAM特征的II期（p46 /mm²）和CD3 （>25.5 /mm²）与转移性疾病相关（p38.5 /mm²）和CD3 （>25.5 /mm²）与较低的复发风险相关（P= 0.014和P= 0.017）。重要的限制是样本量小，复发事件少。结论：这些发现突出了TME与TGCT生物学和预后的相关性。观察到的关联表明，TME可能影响肿瘤的可塑性、转移和复发风险，需要在更大规模的研究中进行验证。

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引用次数: 0

A Systematic Review and Meta-Analysis of the Effectiveness and Safety of Immune Checkpoint Inhibitors in Patients With BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer 免疫检查点抑制剂治疗无bcg反应的非肌肉浸润性膀胱癌的有效性和安全性的系统评价和荟萃分析

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-09-25 DOI: 10.1016/j.clgc.2025.102445

Asmaa Soliman , Mohamed R. Murad , George Jabrieh , Esraa M. AlEdani , Abdelrahman Saeed , Zineddine Belabaci , Thoria I. Essa Ghanm , Israa Ahmed Qutob

The primary cancer of the urinary system is bladder cancer, which includes 2 subtypes: muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Intravesical Bacillus Calmette-Guérin (BCG) therapy remains the gold standard for treating individuals with high-risk NMIBC. However, disease development and recurrence pose serious clinical problems. This study aims to evaluate the safety and efficacy of immune checkpoint inhibitors (ICIs) as innovative therapeutic approaches for patients with BCG-unresponsive NMIBC. We conducted this study according to the PRISMA guidelines. We systematically reviewed clinical trials that evaluated ICIs as a treatment for BCG-unresponsive NMIBC and reported predefined efficacy and safety outcomes. We synthesized data using R software and evaluated the risk of bias using the ROBINS-I tool. Nine studies (488 patients) were included in the review, of which 6 were pooled in the meta-analysis. Following ICI therapy, the complete response (CR) rates were 36% at 3 months, 25% at 6 months, and 18% at twelve months. Across all studies, 14% of patients had a radical cystectomy (RC), with the lowest rates occurring in patients receiving atezolizumab. Treatment-related adverse events (TrAEs) were common, occurring in 15% of patients at grades 3 to 5 and 67% of patients at grades 1 to 2. Adverse events related to the immune system (IrAEs) were noted in 6% of individuals with grades (3-5) and 22% of patients with (grades 1-2). Serious adverse events occurred in 15% of patients overall; the atezolizumab group had a greater incidence (21%) than the pembrolizumab group (11%). Immune checkpoint inhibitors have shown encouraging effectiveness and safety in treating BCG-unresponsive NMIBC. However, the observed variability in therapeutic response and adverse events highlights the necessity for large-scale RCTs to clarify long-term efficacy and inform patient selection for ICI-based therapies.

泌尿系统的原发肿瘤是膀胱癌，包括2种亚型：肌肉浸润性膀胱癌（MIBC）和非肌肉浸润性膀胱癌（NMIBC）。膀胱内卡介苗（BCG）疗法仍然是治疗高危NMIBC患者的金标准。然而，疾病的发展和复发带来了严重的临床问题。本研究旨在评估免疫检查点抑制剂（ICIs）作为bcg无应答的NMIBC患者的创新治疗方法的安全性和有效性。我们根据PRISMA指南进行了这项研究。我们系统地回顾了评估ICIs作为bcg无反应NMIBC治疗方法的临床试验，并报告了预定的疗效和安全性结果。我们使用R软件合成数据，并使用ROBINS-I工具评估偏倚风险。本综述纳入了9项研究（488例患者），其中6项纳入了meta分析。ICI治疗后，3个月时完全缓解率为36%，6个月时为25%，12个月时为18%。在所有研究中，14%的患者进行了根治性膀胱切除术（RC），接受阿特唑单抗的患者发生率最低。治疗相关不良事件（TrAEs）很常见，发生在3 - 5级患者的15%和1 - 2级患者的67%。与免疫系统相关的不良事件（irae）发生在6%的3-5级患者和22%的1-2级患者中。15%的患者发生严重不良事件；阿特唑单抗组的发生率（21%）高于派姆单抗组（11%）。免疫检查点抑制剂在治疗bcg无反应的NMIBC中显示出令人鼓舞的有效性和安全性。然而，观察到的治疗反应和不良事件的可变性突出了大规模随机对照试验的必要性，以阐明长期疗效，并为患者选择基于ci的治疗提供信息。

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引用次数: 0