European urology oncology最新文献_第10页

MicroRNA as a Liquid Biomarker to Detect Malignancy in Small Testicular Masses MicroRNA作为检测小睾丸肿块恶性肿瘤的液体生物标志物。

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology

Pub Date : 2025-12-01 DOI: 10.1016/j.euo.2025.08.004

Julian Chavarriaga , Carley Langleben , João Lobo , Lucia Nappi , George M. Yousef , Gizem Ozcan , Nastaran Khazamipour , Nuno Tiago Tavares , Ioannis Prassas , Lampros Dimitrakopoulos , Xiaotian Yuan , Adam Bobrowski , Susan Prendeville , Lynn Anson-Cartwright , Carmen Jeronimo , Keith Jarvi , Martin O’Malley , Ricardo Leão , Katherine Lajkosz , Robert J. Hamilton

Background and objective

Approximately 1–4% of individuals undergoing scrotal ultrasound are found with incidental small (≤2 cm) testicular masses (STMs), with the vast majority being benign (∼13–21% malignant). This study explores the potential of microRNAs (miRNAs) as liquid biomarkers for predicting germ cell tumors (GCTs) in STMs.

Methods

From 2009 to 2023, we identified patients with STMs who had banked serum/plasma prior to orchiectomy. Eligible samples were analyzed using different miRNA expression methods (reverse transcription quantitative polymerase chain reaction [RT-qPCR] and digital droplet polymerase chain reaction) and platforms across three research laboratory facilities (Portugal, Vancouver, and Toronto). The miRNA assays included 371a-3p, 372, 373, and 367. The primary objective was to evaluate the diagnostic accuracy of miR-371a-3p to predict the presence of testicular cancer using the area under the curve (AUC).

Key findings and limitations

Our cohort included 61 patients: 37 patients with confirmed GCTs, 20 patients with benign histology, and four patients who had been on surveillance for >24 mo and were deemed to have benign STMs. Across all three laboratories, miR-371a-3p consistently outperformed all the miRNAs, with the other miRNAs proving uninformative. Extraction from plasma and an RT-qPCR analysis (Vancouver laboratory) proved best, with sensitivity of 87% and specificity of 91%, translating into an AUC of 0.93. The receiver operating characteristic scores for the other two laboratories were 0.77 and 0.73 for Portugal and Toronto, respectively. This single-center study is limited by a potential selection bias and fewer evaluable samples due to technical and logistical issues.

Conclusions and clinical implications

This is the largest series of STMs with banked blood/serum to date. Among the miRNAs, miR-371a-3p was found to be sensitive and specific for detecting the presence of GCTs in STMs. Plasma with an RT-qPCR approach proved to be a superior method of analysis.

背景和目的：在接受阴囊超声检查的患者中，约有1-4%的患者发现偶发的睾丸小肿块（≤2厘米），其中绝大多数为良性（约13-21%为恶性）。本研究探讨了microRNAs （miRNAs）作为预测STMs生殖细胞肿瘤（gct）的液体生物标志物的潜力。方法：从2009年到2023年，我们确定了在睾丸切除术前有血清/血浆库的STMs患者。在三个研究实验室设施（葡萄牙、温哥华和多伦多）使用不同的miRNA表达方法（逆转录定量聚合酶链反应[RT-qPCR]和数字液滴聚合酶链反应）和平台分析符合条件的样本。miRNA检测包括371a-3p、372、373和367。主要目的是评估miR-371a-3p使用曲线下面积（AUC）预测睾丸癌存在的诊断准确性。主要发现和局限性：我们的队列包括61例患者：37例确诊的gct患者，20例组织学为良性的患者，4例已监测bbbb24个月并被认为是良性STMs的患者。在所有三个实验室中，miR-371a-3p始终优于所有mirna，而其他mirna被证明没有提供信息。从血浆中提取和RT-qPCR分析（温哥华实验室）证明是最好的，灵敏度为87%，特异性为91%，转化为AUC为0.93。葡萄牙和多伦多的其他两个实验室的接收者操作特征得分分别为0.77和0.73。由于技术和后勤问题，该单中心研究受到潜在选择偏差和可评估样本较少的限制。结论和临床意义：这是迄今为止最大的STMs血液/血清库系列。在这些mirna中，发现miR-371a-3p对于检测STMs中gct的存在具有敏感性和特异性。血浆RT-qPCR方法被证明是一种较好的分析方法。

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引用次数: 0

Re: Matthew J. Roberts, Philip Cornford, Derya Tilki. Oncological Benefits of Extended Pelvic Lymph Node Dissection: More Fog or Clarity to the Debate? Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.12.001 回复：Matthew J. Roberts, Philip Cornford, Derya Tilki。扩大盆腔淋巴结清扫的肿瘤学益处：争论更模糊还是更清晰？Urol欧元。在出版社。https://doi.org/10.1016/j.eururo.2024.12.001。

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology

Pub Date : 2025-12-01 DOI: 10.1016/j.euo.2025.01.014

Maria Chiara Sighinolfi , Bernardo Rocco

引用次数: 0

Bladder Cancer with Undetectable Circulating Tumor DNA After Radical Cystectomy May Be Amenable to a Less Intense Imaging Surveillance Protocol: A Diagnostic Accuracy Study 根治性膀胱切除术后循环肿瘤DNA无法检测的膀胱癌可能适用于低强度成像监测方案：诊断准确性研究。

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology

Pub Date : 2025-12-01 DOI: 10.1016/j.euo.2025.04.027

Ahmed Eraky , Reuben Ben-David , Brenda Hug, Kaushik P. Kolanukuduru, Mohammed Almoflihi, Nikhil Waingankar, Kyrollis Attalla, Peter Wiklund, Reza Mehrazin, John P. Sfakianos

Background and objective

Circulating tumor DNA (ctDNA) has shown promise as a prognostic biomarker for bladder cancer management. Current surveillance guidelines for patients with muscle-invasive bladder cancer recommend intense postoperative surveillance. Our aim was to assess the diagnostic performance of ctDNA in comparison to imaging studies for detection of disease recurrence after radical cystectomy.

Methods

We analyzed patients who underwent robot-assisted radical cystectomy and prospective tumor-informed ctDNA analysis (Signatera™) between 2021 and 2023 at a single institution. Patients with postoperative imaging and ctDNA results were included; patients with nonurothelial histology or missing ctDNA data were excluded. Diagnostic accuracy was evaluated at the patient level using imaging findings as the reference standard and ctDNA as the index test. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ctDNA measurement were calculated.

Key findings and limitations

A total of 94 patients were included (median age 70 yr, interquartile range [IQR] 63–77). Most had ≥pT2 disease (75.4%) that was node-negative disease (71.3%). Over median follow-up of 16 mo (IQR 9–22), 388 imaging studies and 283 ctDNA tests were performed. ctDNA demonstrated sensitivity and an NPV of 100.0% (95% confidence interval [CI] 100.0–100.0%), specificity of 91.8% (95% CI 87.6–95.5%), and a PPV of 84.5% (95% CI 76.8–91.3%).

Conclusions and clinical implications

ctDNA measurement may serve as a valuable tool for bladder cancer surveillance after cystectomy. Patients with persistently undetectable ctDNA may benefit from less intensive surveillance protocols aligned with their lower risk of recurrence. This strategy warrants further research to validate its clinical utility and support integration into routine practice.

背景与目的：循环肿瘤DNA （ctDNA）作为膀胱癌预后的生物标志物已显示出前景。目前针对肌肉浸润性膀胱癌患者的监测指南建议加强术后监测。我们的目的是评估ctDNA在根治性膀胱切除术后疾病复发检测中的诊断性能，并与影像学研究进行比较。方法：我们分析了2021年至2023年间在单一机构接受机器人辅助根治性膀胱切除术和前瞻性肿瘤知情ctDNA分析（Signatera™）的患者。纳入患者术后影像学和ctDNA结果；排除非尿路上皮组织学或ctDNA数据缺失的患者。以影像学表现为参考标准，以ctDNA为指标，在患者水平上评估诊断准确性。计算ctDNA检测的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）。主要发现和局限性：共纳入94例患者（中位年龄70岁，四分位数范围[IQR] 63-77）。大多数患有≥pT2疾病（75.4%），淋巴结阴性疾病（71.3%）。中位随访16个月（IQR 9-22），进行了388次影像学检查和283次ctDNA检测。ctDNA的敏感性和NPV为100.0%(95%置信区间[CI] 100.0% -100.0%)，特异性为91.8% (95% CI 87.6-95.5%)， PPV为84.5% （95% CI 768 -91.3%）。结论和临床意义：ctDNA检测可作为膀胱切除术后膀胱癌监测的一种有价值的工具。持续检测不到ctDNA的患者可能受益于与复发风险较低相一致的低强度监测方案。该策略值得进一步研究，以验证其临床效用，并支持整合到日常实践。

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引用次数: 0

The Conundrum of Intermediate Risk in Localised Prostate Cancer: One Group, Many Realities 局部前列腺癌的中间风险难题：一个群体，许多现实。

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology

Pub Date : 2025-12-01 DOI: 10.1016/j.euo.2025.09.017

Arthur Peyrottes , Guillaume Ploussard , Paul Sargos , Eric Barret , Michael Baboudjian

引用次数: 0

A Paradox of Our Time: Evidence-based Guidelines are Blocking Evidence-based Artificial Intelligence 我们这个时代的悖论：基于证据的指导方针阻碍了基于证据的人工智能。

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology

Pub Date : 2025-12-01 DOI: 10.1016/j.euo.2025.10.008

Vincent Misrai , Alena Bruchon

引用次数: 0

Pretreatment Predictors of Pathologic Failure at 1 year After Focal Therapy for Localized Prostate Cancer 局限性前列腺癌局灶治疗后1年病理失败的预处理预测因素。

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology

Pub Date : 2025-12-01 DOI: 10.1016/j.euo.2025.10.004

Anthony Zhang , Nethusan Sivanesan , Preston C. Sprenkle

引用次数: 0

Genomic and Epigenomic Signatures Can Distinguish Aggressive Chromophobe Renal Cell Carcinoma from Indolent Renal Oncocytic Tumors in Clinical-grade Samples 基因组和表观基因组特征可以在临床级样本中区分侵袭性憎色性肾细胞癌和惰性肾嗜瘤性肿瘤。

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology

Pub Date : 2025-12-01 DOI: 10.1016/j.euo.2025.09.018

Roberto Ruiz-Cordero , Qi Wang , Gayatri Kumar , Mahmut Akgul , Chad J. Creighton , Priya Rao , Pheroze Tamboli , Lan Zheng , Jianping Zhao , Paari Murugan , Steven Shen , Fadi Brimo , Ravesanker Ezhilarasan , Erik Sulman , Khalida Wani , Alexander J. Lazar , Taebeom Kim , Ken Chen , Krishna P.L. Bhat , Kasthuri Kannan , Kanishka Sircar

Background and objective

Only a minority of renal oncocytic tumors are aggressive. These tumors’ behavior is difficult to predict by histopathological evaluation; consequently, many patients experience anxiety upon diagnosis and may undergo unnecessary treatment. Our aim was to derive genomic and epigenomic signatures to distinguish clinically indolent renal oncocytic tumors from aggressive chromophobe renal cell carcinoma (ChRCC).

Methods

We performed molecular profiling of nephrectomies from 68 patients: 44 with indolent renal oncocytic tumors (19 renal oncocytoma, two oncocytic renal neoplasm of low malignant potential, and 23 indolent ChRCC) and 24 with aggressive ChRCC. We performed targeted exome sequencing, gene expression profiling, and whole-genome methylation sequencing of formalin-fixed, paraffin-embedded (FFPE) samples. We also analyzed The Cancer Genome Atlas Kidney Chromophobe data from 66 ChRCC patients in silico. Genomic and epigenomic signatures linked to aggressive ChRCC—obtained from sampling morphologically nonsarcomatoid foci—from both cohorts were derived using the least absolute shrinkage and selection operator method.

Key findings and limitations

Aggressive ChRCC was distinguished from indolent ChRCC and other indolent renal oncocytic tumors using a focused seven- to 11-gene expression signature (ten-fold cross-validation [CV] area under the curve [AUC] = 0.77–0.85) with an external validation AUC of 0.88, and an eight-CpG methylation signature (ten-fold CV AUC = 0.86) with an external validation AUC of 0.91. TP53 and PTEN mutations substantially increased the probability of aggressive ChRCC. Limitations include the small sample size.

Conclusions and clinical implications

Focused genomic and epigenomic signatures from routinely processed FFPE tumor tissues can help distinguish aggressive ChRCC from indolent renal oncocytic tumors, including indolent ChRCC. This forms the basis for replication studies to inform appropriate patient management, provide reassurance, and guide follow-up.

背景与目的：只有少数肾嗜瘤细胞肿瘤具有侵袭性。这些肿瘤的行为难以通过组织病理学评估来预测；因此，许多患者在诊断时感到焦虑，并可能接受不必要的治疗。我们的目的是获得基因组和表观基因组特征，以区分临床惰性肾嗜癌性肿瘤和侵袭性憎色肾细胞癌（ChRCC）。方法：我们对68例肾切除术患者进行了分子谱分析：44例为惰性肾嗜酸细胞瘤（19例为肾嗜酸细胞瘤，2例为低恶性潜能肾嗜酸细胞瘤，23例为惰性肾嗜酸细胞癌），24例为侵袭性肾嗜酸细胞癌。我们对福尔马林固定石蜡包埋（FFPE）样品进行了靶向外显子组测序、基因表达谱分析和全基因组甲基化测序。我们还用计算机分析了66例ChRCC患者的癌症基因组图谱肾憎色症数据。与侵袭性chrcc相关的基因组和表观基因组特征——从形态学上的非肉瘤样灶取样中获得——来自两个队列，使用最小绝对收缩和选择算子方法得出。主要发现和局限性：侵袭性ChRCC与惰性ChRCC和其他惰性肾嗜癌性肿瘤的区别在于，使用集中的7至11个基因表达特征（曲线下十倍交叉验证[CV]面积[AUC] = 0.77-0.85），外部验证AUC为0.88，使用8个cpg甲基化特征（十倍CV AUC = 0.86），外部验证AUC为0.91。TP53和PTEN突变显著增加侵袭性ChRCC的可能性。局限性包括样本量小。结论和临床意义：来自常规处理的FFPE肿瘤组织的集中基因组和表观基因组特征可以帮助区分侵袭性ChRCC和惰性肾癌细胞肿瘤，包括惰性ChRCC。这构成了复制研究的基础，为适当的患者管理提供信息，提供保证，并指导随访。

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引用次数: 0

Repeat Prostate Cancer Screening using Blood-based Risk Prediction or Prostate-specific Antigen in the Era of Magnetic Resonance Imaging–guided Biopsies : A Secondary Analysis of the STHLM3-MRI Randomized Clinical Trial 在磁共振成像引导活检时代使用基于血液的风险预测或前列腺特异性抗原进行前列腺癌重复筛查：STHLM3-MRI随机临床试验的二次分析。

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology

Pub Date : 2025-12-01 DOI: 10.1016/j.euo.2024.10.016

Andrea Discacciati , Ahmad Abbadi , Mark S. Clements , Magnus Annerstedt , Stefan Carlsson , Henrik Grönberg , Fredrik Jäderling , Martin Eklund , Tobias Nordström

Background and objective

The use of blood-based risk prediction tools has been proposed to improve prostate cancer screening, but data on repeated screening are lacking. Our aim was to compare outcomes using the blood tests prostate-specific antigen (PSA) and Stockholm3 for repeat prostate cancer screening.

Methods

In the population-based screening-by-invitation STHLM3-MRI trial, men aged 50–74 yr were invited to participate in screening. At 2–3 yr after the initial round, men with PSA ≥1.5 ng/ml at trial inclusion who were randomized to magnetic resonance imaging (MRI)-enhanced screening and were not diagnosed with prostate cancer after the initial round were invited for repeat screening involving analysis of PSA and Stockholm3. Biparametric 1.5-T MRI was performed in cases with PSA ≥3 ng/ml or Stockholm3 ≥0.11. Men with Prostate Imaging0Reporting and Data System ≥3 lesions were referred for targeted plus systematic biopsies. The primary outcome was Gleason ≥7 cancer. Secondary outcomes included the number of MRI scans and biopsy procedures, and detection of Gleason 6 and Gleason ≥4 + 3 cancer. Outcomes were compared using the relative positive fractions (RPF).

Key findings and limitations

Of 7609 men from the initial screening round, 2078 were eligible for repeat screening and 1500 (72%) participated. For detection of Gleason ≥7 prostate cancer, the area under the receiver operating characteristic curve was 0.765 (95% confidence interval [CI] 0.725–0.805) for Stockholm3 and 0.651 (95% CI 0.601–0.701) for PSA. Stockholm3 ≥0.15 was associated with 41% fewer MRI scans in comparison to PSA ≥3 ng/ml (RPF 0.59, 95%CI 0.54–0.64), while the detection of GS ≥4 + 3 cancers was similar (RPF 1.00, 95% CI 0.78–1.29). Stockholm3 ≥0.15 detected fewer Gleason ≥7 (RPF 0.75, 95% CI 0.59–0.95) and Gleason 6 (RPF 0.73, 95% CI 0.46–1.16) cancers. Stockholm3 ≥0.11 was associated with no decrease in the number of MRI scans, but an increase of the number of cancer cases detected. Limitations include the lack of long-term outcomes.

Conclusions and clinical implications

Use of the Stockholm3 test for repeated prostate cancer screening could reduce the need for MRI while maintaining detection rates for high-risk cancer.

Patient summary

In this study, we invited men to a second round of prostate cancer screening. We found that use of a new blood test called Stockholm3 can make screening programs more efficient by using fewer resources while still detecting aggressive cancers.

背景和目的：有人提出使用基于血液的风险预测工具来改善前列腺癌筛查，但缺乏重复筛查的数据。我们的目的是比较使用血液检测前列腺特异性抗原（PSA）和斯德哥尔摩3指数进行前列腺癌重复筛查的结果：在基于人群的邀请筛查 STHLM3-MRI 试验中，50-74 岁的男性被邀请参加筛查。在首轮筛查结束后 2-3 年，随机接受磁共振成像（MRI）增强筛查且在首轮筛查后未被确诊为前列腺癌的男性被邀请进行重复筛查，其中包括 PSA 和 Stockholm3 分析。对PSA≥3纳克/毫升或Stockholm3≥0.11的病例进行双参数1.5T磁共振成像检查。前列腺成像0报告和数据系统≥3病变的男性将被转诊进行靶向加系统活检。主要结果是Gleason≥7癌症。次要结果包括 MRI 扫描和活检次数，以及 Gleason 6 和 Gleason ≥4 + 3 癌症的检出率。结果采用相对阳性率（RPF）进行比较：在首轮筛查的 7609 名男性中，有 2078 人符合重复筛查的条件，其中 1500 人（72%）参加了重复筛查。在检测格里森≥7的前列腺癌时，斯德哥尔摩3型的接收者操作特征曲线下面积为0.765（95%置信区间[CI] 0.725-0.805），PSA的接收者操作特征曲线下面积为0.651（95%置信区间[CI] 0.601-0.701）。与 PSA ≥3 ng/ml 相比，Stockholm3 ≥0.15 与 MRI 扫描次数减少 41% 相关（RPF 0.59，95%CI 0.54-0.64），而 GS ≥4 + 3 癌症的检出率相似（RPF 1.00，95% CI 0.78-1.29）。Stockholm3≥0.15检出的Gleason≥7（RPF 0.75，95% CI 0.59-0.95）和Gleason 6（RPF 0.73，95% CI 0.46-1.16）癌症较少。Stockholm3≥0.11与核磁共振成像扫描次数的减少无关，但与癌症病例检测次数的增加有关。不足之处包括缺乏长期结果：在前列腺癌重复筛查中使用斯德哥尔摩 3 检验可减少对核磁共振成像的需求，同时保持高风险癌症的检出率。患者摘要：在这项研究中，我们邀请男性参加第二轮前列腺癌筛查。我们发现，使用一种名为 "Stockholm3 "的新型血液检验可以减少筛查资源的使用，从而提高筛查项目的效率，同时还能检测出侵袭性癌症。

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引用次数: 0

Robotic Versus Open Radical Prostatectomy, Differences in Prostate Cancer–specific Survival—12 Years of Follow-up in the LAParoscopic Prostatectomy Robot Open Trial 机器人与开放式根治性前列腺切除术，前列腺癌特异性生存率的差异——腹腔镜前列腺切除术机器人开放试验12年随访

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology

Pub Date : 2025-12-01 DOI: 10.1016/j.euo.2025.05.004

Anna Lantz , Ying Li , Stefan Carlsson , Johan Stranne , Eva Angenete , Olof Akre , Anders Bjartell , Mehbod Mansoori , Carolina Ehrencrona , Peter Wiklund , Eva Haglind

Background and objective

Localized prostate cancer can be treated with either robot-assisted laparoscopic prostatectomy (RALP) or open retropubic radical prostatectomy (RRP). This study aimed to analyze all-cause and prostate cancer–specific mortality 12 yr after surgery.

Methods

The nonrandomized multicenter LAParoscopic Prostatectomy Robot Open (LAPPRO) trial enrolled patients from 2008 to 2011. The eligibility criteria included age <75 yr, prostate-specific antigen <20 ng/ml, clinical stage <T4, nonmetastatic disease, and informed consent. Data were collected through validated questionnaires at baseline and clinical record forms repeatedly up to 12 yr after surgery, with mortality information retrieved from Sweden’s National Cause of Death Register. The main outcomes were all-cause and prostate cancer–specific mortality.

Key findings and limitations

Of the 4003 patients enrolled in LAPPRO, 3583 were eligible for the current analysis, of whom 2698 (75%) underwent RALP and 885 (25%) RRP. At 12 yr after surgery, prostate cancer–specific mortality was significantly lower after RALP than after RRP (55/2698 [2.0%] vs 40/885 [4.5%]; adjusted hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.23–0.55). The numbers of all-cause deaths were 371/2698 (14%) in the RALP group and 145/885 (16%) in the RRP group (adjusted HR 0.81, 95% CI 0.66–0.99). The study is limited by its nonrandomized design.

Conclusions and clinical implications

At 12 yr after surgery, prostate cancer–specific mortality was significantly lower in patients undergoing robotic prostatectomy than in those undergoing open prostatectomy. Cautious interpretation is suggested for the possible causal effect, but the results suggest that the robotic technique is associated with a better oncological outcome.

背景与目的：机器人辅助腹腔镜前列腺切除术（RALP）或开放性耻骨后根治性前列腺切除术（RRP）可以治疗局限性前列腺癌。本研究旨在分析手术后12年的全因死亡率和前列腺癌特异性死亡率。方法：非随机多中心腹腔镜前列腺切除术机器人公开赛（LAPPRO）试验于2008年至2011年纳入患者。入选标准包括年龄。主要发现和局限性：纳入LAPPRO的4003例患者中，3583例符合当前分析，其中2698例（75%）接受了RALP， 885例（25%）接受了RRP。术后12年，RALP组前列腺癌特异性死亡率显著低于RRP组（55/2698 [2.0%]vs 40/885 [4.5%]）；校正风险比[HR] 0.36, 95%可信区间[CI] 0.23-0.55)。RALP组的全因死亡人数为371/2698 (14%)，RRP组为145/885(16%)（校正HR 0.81, 95% CI 0.66-0.99）。该研究因其非随机设计而受到限制。结论和临床意义：手术后12年，机器人前列腺切除术患者的前列腺癌特异性死亡率明显低于开放式前列腺切除术患者。对可能的因果关系提出了谨慎的解释，但结果表明，机器人技术与更好的肿瘤预后有关。

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引用次数: 0

Endoscopic Thulium Laser Ablation with Disitamab Vedotin and Immunotherapy in High-risk Upper Tract Urothelial Carcinoma: A Prospective Pilot Study of a Novel Kidney-sparing Strategy 内镜下铥激光消融联合地西他单维多汀和免疫治疗高危上尿路癌：一项新的肾保留策略的前瞻性先导研究。

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology

Pub Date : 2025-12-01 DOI: 10.1016/j.euo.2025.09.015

Jianjun Ye , Zeyu Chen , Xinyang Liao , Shiyu Zhang , Xiang Tu , Qihao Wang , Lei Zheng , Kai Chen , Banghua Liao , Mengni Zhang , Yali Shen , Jiyan Liu , Shuang Zhang , Hanmei Zhang , Peng Zhang , Hao Zeng , Xiang Li , Qiang Wei , Yige Bao

Background and objective

Kidney-sparing treatment (KST) is an emerging alternative to radical nephroureterectomy for selected patients with upper tract urothelial carcinoma (UTUC), particularly those with imperative indications. Our aim was to evaluate the efficacy and safety of a novel KST approach combining endoscopic thulium laser ablation (TLA) with perioperative systemic therapy (disitamab vedotin [DV] and an immune checkpoint inhibitor [ICI]; toripalimab or tislelizumab) in a carefully selected cohort of patients with localized high-risk UTUC.

Methods

This single-center prospective pilot study conducted from June 2021 to February 2024 and enrolled patients with localized high-risk UTUC with HER2 expression. Patients underwent multimodal treatment comprising sequential induction therapy, endoscopic TLA, consolidation therapy, and maintenance therapy. Co-primary endpoints were local recurrence–free survival (LRFS) and conversion-free survival (CFS). Secondary endpoints included overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), intravesical recurrence–free survival (IVRFS), renal function benefits, and therapy-related adverse events (TRAEs).

Key findings and limitations

A total of 33 patients were enrolled. Median follow-up was 23 mo for those without death or salvage surgery. LRFS rates were 67% at 1 yr and 64% at 2 yr. HER2 positivity was identified as a candidate protective factor for local recurrence within the first year (odds ratio 0.12, 95% confidence interval 0.01–0.95; p = 0.042). The 2-yr survival rates were 94% for CFS, 88% for IVRFS,100% for MFS, 94% for OS, and 100% for CSS. A renal function benefit was observed within the first year after ablation. The 1-yr ureteral stricture rate was 12% and no grade >3 TRAEs were observed.

Conclusions and clinical implications

The combination of endoscopic TLA with perioperative systemic therapy demonstrated promising efficacy and manageable safety in selected patients with localized high-risk UTUC. Our results suggest that there is potential for a paradigm shift in the management of this challenging patient population.

背景和目的：对于上尿路上皮癌（UTUC）患者，尤其是那些有迫切适应症的患者，肾保留治疗（KST）是一种新兴的替代根治性肾输尿管切除术的方法。我们的目的是评估一种新的KST方法联合内镜下激光消融（TLA）与围手术期全身治疗（地西他麦维多汀[DV]和免疫检查点抑制剂[ICI]；托利单抗或替利单抗）在精心挑选的局部高危UTUC患者中的疗效和安全性。方法：这项单中心前瞻性先导研究于2021年6月至2024年2月进行，纳入了HER2表达的局部高危UTUC患者。患者接受多模式治疗，包括序贯诱导治疗、内窥镜TLA、巩固治疗和维持治疗。共同主要终点是局部无复发生存期（LRFS）和无转化生存期（CFS）。次要终点包括总生存期（OS）、癌症特异性生存期（CSS）、无转移生存期（MFS）、膀胱内无复发生存期（IVRFS）、肾功能获益和治疗相关不良事件（TRAEs）。主要发现和局限性：共入组33例患者。中位随访时间为23个月，无死亡或抢救性手术。LRFS在1年和2年分别为67%和64%。HER2阳性被确定为第一年局部复发的候选保护因素（优势比0.12,95%可信区间0.01-0.95;p = 0.042）。CFS的2年生存率为94%，IVRFS为88%，MFS为100%，OS为94%，CSS为100%。消融后一年内观察到肾功能改善。1年输尿管狭窄发生率为12%，未观察到bbb3级trae。结论及临床意义：内镜下TLA联合围手术期全身治疗对局部高危UTUC患者具有良好的疗效和可管理的安全性。我们的研究结果表明，在这一具有挑战性的患者群体的管理中，有可能发生范式转变。

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引用次数: 0