Clinical genitourinary cancer最新文献_第8页

Titrating Cabozantinib in Metastatic Renal Cell Carcinoma Patients Using Goldilocks Principle: A Real-World Evidence Study 用金凤花原则在转移性肾细胞癌患者中滴定卡博赞替尼：一项真实世界的证据研究

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-08-31 DOI: 10.1016/j.clgc.2025.102419

Malou Aarønæs Thybo , Johanne Ahrenfeldt , Iben Lyskjær , Niels Fristrup

Introduction

The incidence of renal cell carcinoma (RCC) continues to rise worldwide, and this malignancy has demonstrated substantial sensitivity to both immunotherapies and targeted agents, particularly tyrosine kinase inhibitors (TKIs). Cabozantinib, a commonly utilized TKI, has shown promising efficacy across multiple clinical trials. This study aims to evaluate the real-world effectiveness of individualized cabozantinib dosing as a later-line treatment in patients with metastatic RCC (mRCC).

Patients and methods

Patients with mRCC treated at the Department of Oncology, Aarhus University Hospital, Denmark, were identified to estimate the median progression free survival (mPFS) and median overall survival (mOS) from treatment initiation. Best radiological response was evaluated using RECIST 1.1. Multivariable cox regression analyses were performed, including covariates such as brain metastasis, first-line treatment, line of treatment, ECOG Performance Status, IMDC risk group, nephrectomy status, and toxicity.

Results

A total of 179 patients were included, of which 139 patients received second-line (2L) treatment, and 40 patients received third+-line (3+L) treatment. We found a mPFS of 11.2 months for 2L treatment and 11.6 months for 3+L treatment. The mOS was 15.6 months for the 2L group and 17.1 months for the 3+L group. The mPFS and mOS in the IMDC favourable risk group were 28.5 and 52.1 months, respectively. No significant differences in mPFS or mOS were observed based on prior 1L treatment or the presence of brain metastases. The mOS and mPFS found in this study are comparable to, and in some cases exceed, those reported in other real-world cohorts. Interestingly, we found treatment-related toxicity to correlate significantly with an increased survival (mOS 66.8 vs. 32.8 months, P = .016) (mPFS 14,7 vs. 8,5 months, P = .013).

Conclusion

This study reinforces the existing data on effectiveness of cabozantinib as a later-line treatment for mRCC in real-world settings. We report 40 mg as the preferred landing zone. Furthermore we identify patients needing dose reductions due to toxicity as a subgroup carrying a significantly better prognosis. The results emphasize the importance of individual dosage for optimizing treatment outcomes and points out treatment-related toxicity as a surrogate marker for sufficient serum concentration of the active substance.

肾细胞癌（RCC）的发病率在全球范围内持续上升，这种恶性肿瘤对免疫疗法和靶向药物，特别是酪氨酸激酶抑制剂（TKIs）都表现出相当大的敏感性。Cabozantinib是一种常用的TKI，在多个临床试验中显示出良好的疗效。本研究旨在评估个体化cabozantinib剂量作为转移性肾细胞癌（mRCC）患者后期治疗的实际有效性。在丹麦奥胡斯大学医院肿瘤科接受治疗的mRCC患者被确定，以估计从治疗开始的中位无进展生存期（mPFS）和中位总生存期（mOS）。采用RECIST 1.1评价最佳放射反应。进行多变量cox回归分析，包括脑转移、一线治疗、治疗线、ECOG表现状态、IMDC危险组、肾切除术状态和毒性等协变量。结果共纳入179例患者，其中二线（2L）治疗139例，三线+线（3+L）治疗40例。我们发现2L治疗的mPFS为11.2个月，3+L治疗的mPFS为11.6个月。2L组最小生存期为15.6个月，3+L组最小生存期为17.1个月。IMDC有利风险组的mPFS和mOS分别为28.5个月和52.1个月。基于先前的l治疗或脑转移的存在，未观察到mPFS或mOS的显著差异。本研究中发现的mOS和mPFS与其他现实世界队列的报告相当，在某些情况下甚至超过了这些报告。有趣的是，我们发现治疗相关的毒性与生存期的增加显著相关（最长生存期66.8个月vs. 32.8个月，P = 0.016）（最长生存期14,7个月vs. 8,5个月，P = 0.013）。结论：本研究强化了cabozantinib作为mRCC后期治疗在现实环境中的有效性的现有数据。我们报告40毫克为首选着陆区。此外，我们确定由于毒性需要减少剂量的患者作为预后明显较好的亚组。结果强调了个体剂量对优化治疗结果的重要性，并指出治疗相关毒性是有效物质足够血清浓度的替代标志。

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引用次数: 0

Trends in Treatment Patterns and Outcomes Among Patients Diagnosed With Nonmuscle-Invasive Bladder Cancer in the United States 美国非肌肉浸润性膀胱癌患者的治疗模式和预后趋势

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-08-29 DOI: 10.1016/j.clgc.2025.102424

Bernard Bright Davies-Teye , Dominique Seo , Abree Johnson , Jennifer Stuart , Mehmet Burcu , Nader Hanna , Eberechukwu Onukwugha , M. Minhaj Siddiqui

Introduction

Heterogeneity in disease presentation in nonmuscle invasive bladder cancer (NMIBC) creates significant variability in treatment patterns and outcomes across risk and clinical subgroups.

Methods

A descriptive analysis of NMIBC patients diagnosed between 2004 and 2017 using the National Cancer Database (NCDB), examined trends and patterns in treatment practices, postradical cystectomy (RC) outcomes, and survival overall and by subgroups. The American Urological Association/Society of Urologic Oncology risk stratification guideline was used to categorize patients into low-intermediate (LIR) and high-risk groups.

Results

Among newly diagnosed NMIBC patients (N = 324,646), 78.6% received TURBT without BCG, and 17.4% received BCG as part of their first course of treatment. Treatment patterns differed by risk groups. The high-risk group had lower TURBT without BCG than LIR (64.7% vs. 90.8%), but higher BCG (28.3% vs. 8.0%) and RC (5.5% vs. 0.5%). In the high-risk group, BCG and RC rates were higher in cT1/cTs than cTa patients. Over time, from 2004-2008 to 2013-2017, the use of BCG (12.6%-21.3%) and RC (2.2%-3.0%) increased, while TURBT-without BCG (84.3%-74.5%) decreased. Post-RC 90-day mortality was higher in high-risk than in LIR patients (4.6% vs. 2.8%). Five-year survival probabilities were unchanged over time. A post-hoc analysis revealed that 14% of patients received postoperative intravesical chemotherapy, with no notable differences in patient characteristics between this subgroup and the overall population.

Conclusion

Unmet medical needs for NMIBC patients persist, as many high-risk patients do not receive guideline-recommended care, and survival outcomes remain largely unchanged.

简介：非肌肉浸润性膀胱癌（NMIBC）疾病表现的异质性导致不同风险和临床亚组的治疗模式和结果存在显著差异。方法：使用国家癌症数据库（NCDB）对2004年至2017年诊断的NMIBC患者进行描述性分析，检查治疗实践的趋势和模式、术后膀胱切除术（RC）结果以及总体和亚组生存率。采用美国泌尿外科协会/泌尿肿瘤学会风险分层指南将患者分为中低危组（LIR）和高危组。结果：在新诊断的NMIBC患者（N = 324,646）中，78.6%的患者接受了不含BCG的TURBT治疗，17.4%的患者在首个疗程中接受了BCG治疗。治疗模式因风险组而异。高危组无BCG的TURBT低于LIR (64.7% vs. 90.8%)，但BCG （28.3% vs. 8.0%）和RC （5.5% vs. 0.5%）较高。在高危组中，cT1/ ct患者中BCG和RC的发生率高于cTa患者。随着时间的推移，从2004-2008年到2013-2017年，BCG的使用（12.6%-21.3%）和RC（2.2%-3.0%）增加，而不使用BCG的turbt（84.3%-74.5%）减少。术后90天死亡率高危组高于LIR组（4.6% vs. 2.8%）。五年生存率随着时间的推移没有变化。事后分析显示，14%的患者接受了术后膀胱内化疗，该亚组患者特征与总体人群无显著差异。结论：NMIBC患者的医疗需求仍未得到满足，因为许多高危患者未接受指南推荐的治疗，生存结果基本保持不变。

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引用次数: 0

Addressing Uneven Treatment Discontinuation Rate in the Chemotherapy Arm of the EV-302 Phase 3 Randomized Clinical Trial: Implications for Outcome Interpretation 解决EV-302 iii期随机临床试验化疗组治疗停药率不均匀问题：对结果解释的影响

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-08-28 DOI: 10.1016/j.clgc.2025.102423

Daniele Robesti , Filippo Micheli , Shesh N. Rai , Giuseppe Fallara , Andrea Gallina , Francesco Montorsi , Alberto Briganti , Nicola Fossati , Petros Grivas , Antoine G. van der Heijden , Guillaume Ploussard , Bernard Malavaud , Alberto Martini

Introduction

The EV-302 trial demonstrated a very significant overall survival (OS) benefit for Enfortumab Vedotin plus Pembrolizumab (EVP) relative to standard chemotherapy (CHT) for patients with metastatic urothelial carcinoma. However, questions have been raised regarding the high rate of treatment discontinuation in the CHT arm for reasons unrelated to adverse events or progression (33% vs. 10% with EVP, P < .01), potentially resulting in loss of unaccounted information, or informative censoring, and affecting survival results interpretation.

Materials and Methods

We performed a multistep analysis to assess the impact of differential dropout on trial outcomes. First, Kaplan–Meier (KM) curves were reconstructed from published data to estimate time-to-event outcomes. Second, a reverse KM analysis was conducted to evaluate censoring patterns in the overall population and key subgroups (PD-L1 expression; cisplatin eligibility). Third, simulation models were employed to test whether informative censoring could negatively impact survival benefit by EVP. Finally, we compared the CHT arm of EV-302 to those of other contemporary RCTs through reconstructed survival analyses and risk-of-bias assessments.

Results

Overall, no significant imbalance in censoring between the treatment arms of EV-302 was found on reverse KM analysis when assessing OS (P = .73); however, a significant difference was noted for progression-free survival (PFS) (P = .002). Simulation analysis revealed that even under extreme assumptions of informative censoring, the OS benefit of EVP remained statistically significant. Comparison with historical RCTs confirmed that the CHT outcomes in EV-302 were not anomalously poor. Risk of bias was low overall, although deviations from intervention and outcome measurement were flagged for EV-302.

Conclusions

Despite the high discontinuation rate in the CHT arm, OS benefit with EVP remains robust. These findings support the reliability of EV-302 results and mitigate concerns about informative censoring, thus encouraging the use of EVP in clinical practice.

EV-302试验表明，与标准化疗（CHT）相比，对于转移性尿路上皮癌患者，Enfortumab Vedotin联合Pembrolizumab （EVP）具有非常显著的总生存期（OS）益处。然而，由于与不良事件或进展无关的原因（33% vs. EVP组的10%，P < 0.01）， CHT组的高停药率也引起了质疑，这可能导致未解释信息的丢失，或信息审查，并影响生存结果的解释。材料和方法：我们进行了多步骤分析来评估差异退出对试验结果的影响。首先，根据已发表的数据重建Kaplan-Meier （KM）曲线，以估计事件发生的时间。其次，进行反向KM分析以评估总体人群和关键亚组（PD-L1表达；顺铂资格）的筛选模式。第三，采用仿真模型检验信息审查是否会对EVP的生存效益产生负面影响。最后，我们通过重构生存分析和偏倚风险评估，将EV-302的CHT组与其他当代随机对照试验进行了比较。结果：总体而言，在评估OS时，反向KM分析中未发现EV-302治疗组之间的审查不平衡（P = 0.73）；然而，无进展生存期（PFS）有显著差异（P = 0.002）。模拟分析显示，即使在信息审查的极端假设下，EVP的操作系统效益仍然具有统计学意义。与历史随机对照试验的比较证实，EV-302的CHT结果并没有异常差。总体上偏倚风险较低，尽管干预和结果测量的偏差被标记为EV-302。结论：尽管在CHT组中有很高的停药率，EVP的OS获益仍然强劲。这些发现支持EV-302结果的可靠性，减轻了对信息审查的担忧，从而鼓励在临床实践中使用EVP。

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引用次数: 0

Impact of Upstaging From cT2a-b to pT3a on Overall Survival Among Patients With Renal Cell Carcinoma 从cT2a-b到pT3a对肾癌患者总生存期的影响

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-08-28 DOI: 10.1016/j.clgc.2025.102422

Taylor Goodstein , Rajvi Goradia , Arnav Srivastava , Akshay Sood , Shawn Dason , Viraj A. Master , Eric A. Singer

Introduction and objectives

Identifying patients with renal cell carcinoma (RCC) who may benefit from adjuvant systemic therapy has proven difficult. Approximately 40% of patients with cT2 tumors will be upstaged to pT3a disease following surgery. These patients, given their large tumor size, may represent a higher risk cohort as compared to patients with concordant T3a staging. We assessed OS among cT2 patients who were upstaged to pT3a compared to their cT3a counterparts with concordant pathologic staging.

Methods

Using the National Cancer Database, we identified N0M0 adult patients with cT2a, cT2b, and cT3a RCC who underwent partial or radical nephrectomy and had pT3a disease on final pathology. We categorized patients into 3 groups: (1) cT2a to pT3a, (2) cT2b to pT3a, and (3) cT3a to pT3a. We compared OS between the groups using Kaplan Meier estimates and multivariable analysis using Cox proportional hazards models. Subgroup analysis of overall survival was performed for histology (clear cell vs. non–clear cell).

Results

About 11,241 patients met inclusion criteria (3,067 cT2a, 1,893 cT2b, and 6,281 cT3a). Median pathological tumor size was 8.2, 12.2, and 7.1 cm for cT2a, cT2b and cT3a tumors, respectively. 5-year OS was 37% for both cT2a and cT2b disease upstaged to pT3a and 48% for cT3a disease with concordant pathological staging (P < .0001). This finding persisted on multivariable analysis (cT3a HR 0.81 [0.77–0.85], P < .001).

Conclusions

Patients who were pathologically upstaged from cT2 to pT3a disease had worse OS compared to patients with concordant staging. Our findings imply that it is reasonable to include well-selected cT2 tumors in the next iteration of perioperative trials.

介绍和目的：鉴别可能受益于辅助全身治疗的肾细胞癌（RCC）患者已被证明是困难的。大约40%的cT2肿瘤患者在手术后会被pT3a疾病所取代。这些患者，由于其肿瘤大小较大，与一致T3a分期的患者相比，可能代表更高的风险队列。我们评估了与病理分期一致的cT3a患者相比，被抢到pT3a的cT2患者的OS。方法：使用国家癌症数据库，我们确定了N0M0例cT2a、cT2b和cT3a RCC的成人患者，他们接受了部分或根治性肾切除术，最终病理为pT3a疾病。我们将患者分为3组：(1)cT2a至pT3a， (2) cT2b至pT3a， (3) cT3a至pT3a。我们使用Kaplan Meier估计和Cox比例风险模型的多变量分析来比较各组间的OS。对组织学（透明细胞与非透明细胞）进行总生存率亚组分析。结果：约11241例患者符合纳入标准（3067例cT2a， 1893例cT2b和6281例cT3a）。cT2a、cT2b和cT3a肿瘤的中位病理大小分别为8.2、12.2和7.1 cm。cT2a和cT2b被pT3a抢占的5年OS为37%，病理分期一致的cT3a为48% （P < 0.0001）。这一发现在多变量分析中仍然存在（cT3a HR 0.81 [0.77-0.85], P < .001）。结论：病理上从cT2转移到pT3a的患者比分期一致的患者有更差的OS。我们的研究结果表明，在下一次围手术期试验中纳入精心挑选的cT2肿瘤是合理的。

{"title":"Impact of Upstaging From cT2a-b to pT3a on Overall Survival Among Patients With Renal Cell Carcinoma","authors":"Taylor Goodstein , Rajvi Goradia , Arnav Srivastava , Akshay Sood , Shawn Dason , Viraj A. Master , Eric A. Singer","doi":"10.1016/j.clgc.2025.102422","DOIUrl":"10.1016/j.clgc.2025.102422","url":null,"abstract":"<div><h3>Introduction and objectives</h3><div>Identifying patients with renal cell carcinoma (RCC) who may benefit from adjuvant systemic therapy has proven difficult. Approximately 40% of patients with cT2 tumors will be upstaged to pT3a disease following surgery. These patients, given their large tumor size, may represent a higher risk cohort as compared to patients with concordant T3a staging. We assessed OS among cT2 patients who were upstaged to pT3a compared to their cT3a counterparts with concordant pathologic staging.</div></div><div><h3>Methods</h3><div>Using the National Cancer Database, we identified N0M0 adult patients with cT2a, cT2b, and cT3a RCC who underwent partial or radical nephrectomy and had pT3a disease on final pathology. We categorized patients into 3 groups: (1) cT2a to pT3a, (2) cT2b to pT3a, and (3) cT3a to pT3a. We compared OS between the groups using Kaplan Meier estimates and multivariable analysis using Cox proportional hazards models. Subgroup analysis of overall survival was performed for histology (clear cell vs. non–clear cell).</div></div><div><h3>Results</h3><div>About 11,241 patients met inclusion criteria (3,067 cT2a, 1,893 cT2b, and 6,281 cT3a). Median pathological tumor size was 8.2, 12.2, and 7.1 cm for cT2a, cT2b and cT3a tumors, respectively. 5-year OS was 37% for both cT2a and cT2b disease upstaged to pT3a and 48% for cT3a disease with concordant pathological staging (<em>P</em> < .0001). This finding persisted on multivariable analysis (cT3a HR 0.81 [0.77–0.85], <em>P</em> < .001).</div></div><div><h3>Conclusions</h3><div>Patients who were pathologically upstaged from cT2 to pT3a disease had worse OS compared to patients with concordant staging. Our findings imply that it is reasonable to include well-selected cT2 tumors in the next iteration of perioperative trials.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102422"},"PeriodicalIF":2.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082725","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

Rising Trends of Aggressive Renal Cell Carcinoma Among Younger Adults: Insights From the National Cancer Database 年轻人侵袭性肾细胞癌的上升趋势：来自国家癌症数据库的见解。

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-08-27 DOI: 10.1016/j.clgc.2025.102425

Giuseppe Garofano , Cesare Saitta , Giacomo Musso , Margaret F. Meagher , Umberto Capitanio , Dhruv Puri , Mai Dabbas , Natalie Birouty , Sanjana Karamcheti , Breanna Kim , Kit L. Yuen , Alessandro Larcher , Benjamin Baker , Riccardo Autorino , Savio D. Pandolfo , Francesco Montorsi , Alberto Saita , Massimo Lazzeri , Giovanni Lughezzani , Paolo Casale , Ithaar H. Derweesh

Objective

To evaluate trends, and characteristics of renal cell carcinoma (RCC) in younger adults, as its rise has been primarily attributed to increasing incidental discovery of small renal masses in older adults.

Methods

We utilized the National Cancer Database to examine RCC patients aged 20-39 years between 2004 and 2021. Annual Average Percent Change (AAPC) was estimated via negative binomial regression. Aggressive RCC was defined as pT3+, high-grade (G3/G4), pN1, or metastatic disease. Logistic regression identified risk factors for aggressive RCC. Kaplan-Meier and Cox models assessed survival impact.

Results

Among 30,849 RCC cases, 8,465 (27.45%) were classified as aggressive RCC. The number of diagnosed cases increased over time (AAPC: 3.53%, P < .001), with aggressive RCC increasing at a similar rate (AAPC: 3.58%, P < .001). Compared to clear cell RCC, papillary (OR = 1.49, P < .001), chromophobe (OR = 1.14, P = .006), collecting duct (OR = 35.68, P < .001), and RCC NOS (OR = 1.51, P < .001) had higher odds of aggressive RCC. Black (OR = 1.53, P < .001) and Asian/Pacific Islander patients (OR = 1.51, P < .001) were more likely to present with aggressive RCC compared to White patients. Uninsured (OR = 1.18, P = .001) and unknown insurance status patients (OR = 1.49, P < .001) had significantly higher odds of aggressive RCC compared to privately insured patients. At 120 months, survival was significantly lower for aggressive vs nonaggressive RCC (65.0% vs. 91.7%, P < .001). The negative impact of aggressive RCC on survival was attenuated in patients aged ≥ 35 years (HR = 0.78, P = .001)

Conclusion

Rising RCC cases in younger adults are accompanied by an increase in aggressive disease, not attributable to stage migration. The drivers for this rise are unclear and demand more investigation.

目的：评估年轻人肾细胞癌（RCC）的趋势和特征，因为其上升主要归因于老年人偶然发现的小肾肿块的增加。方法：我们利用国家癌症数据库对2004年至2021年间20-39岁的RCC患者进行调查。通过负二项回归估计年平均变化百分率（AAPC）。侵袭性RCC被定义为pT3+、高级别（G3/G4）、pN1或转移性疾病。Logistic回归确定了侵袭性肾细胞癌的危险因素。Kaplan-Meier和Cox模型评估了生存影响。结果：30849例RCC中，8465例（27.45%）为侵袭性RCC。随着时间的推移，诊断病例数增加（AAPC: 3.53%, P < 0.001），侵袭性RCC的增加率相似（AAPC: 3.58%, P < 0.001）。与透明细胞RCC相比，乳头状（OR = 1.49, P < 0.001）、嫌色细胞（OR = 1.14, P = 0.006）、收集管（OR = 35.68, P < 0.001）和RCC NOS （OR = 1.51, P < 0.001）发生侵袭性RCC的几率更高。与白人患者相比，黑人患者（OR = 1.53, P < .001）和亚洲/太平洋岛民患者（OR = 1.51, P < .001）更有可能出现侵袭性肾细胞癌。未参保患者（OR = 1.18, P = .001）和参保状况不明患者（OR = 1.49, P < .001）发生侵袭性肾细胞癌的几率显著高于参保患者。在120个月时，侵袭性RCC的生存率明显低于非侵袭性RCC（65.0%对91.7%,P < 0.001）。在年龄≥35岁的患者中，侵袭性RCC对生存的负面影响减弱（HR = 0.78, P = .001）。结论：年轻成人中RCC病例的增加伴随着侵袭性疾病的增加，而不是归因于分期迁移。这一增长的驱动因素尚不清楚，需要更多的调查。

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引用次数: 0

Discovery of TBK1-Associated Oncogenic Mechanisms in Patients With Upper Tract Urothelial Carcinoma and Pre-Existing End-Stage Renal Disease tbk1在上尿路上皮癌和终末期肾病患者中相关的致癌机制的发现

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-08-21 DOI: 10.1016/j.clgc.2025.102420

Yu-Pin Huang , Jen-Chieh Chen , Yu-Ching Peng , Yu-Kuang Chen , William J. Huang , Cih-Yu Jheng , Yi-Ting Liao , Eric Yi-Hsiu Huang , Kung-Hao Liang

Background

Upper tract urothelial carcinoma is an aggressive malignancy originating from the transitional epithelium of the urinary tract. UTUC patients with pre-existing end stage renal disease (ESRD) have limited perioperative treatment options due to severely impaired bilateral kidney functions. We therefore sought to identify targetable oncogenic mechanisms in this patient population.

Methods

A single-center retrospective study analyzed 50 fresh frozen UTUC tumor samples (17 with ESRD, 33 without) using RNA sequencing for transcriptomics profiling. Gene set enrichment analysis was performed to identify gene sets collectively enriched in ESRD tumors, with normalized enrichment score (NES) used to standardize enrichment magnitude across sets of varying sizes. Regular hemodialysis prior to UTUC diagnosis was used to identify patients with ESRD. Immunohistochemical staining was conducted on paraffin-embedded slides (6 with ESRD, 7 without) to demonstrate the involvement of representative proteins in the gene set. Candidate drugs were ranked via Connectivity Map analysis, and the drug with the highest inhibition score were further assessed through in vitro cell viability and migration assays.

Results

Because overall and cancer‑specific survival did not differ significantly between groups, we interpreted transcriptomic differences as intrinsic tumor characteristics rather than consequences of disease severity. TBK1-associated gene sets were enriched in ESRD-UTUC patients (NES = 2.065, FDR q value = 0.001). Immunohistochemistry confirmed higher TBK1 levels in ESRD tissues (P = .044). A IKK/NF-κB inhibitor, Withaferin A (CAS No. 5119-48-2), emerged as a leading candidate drug (score of inhibition = 2.521). The in vitro assays demonstrated the effectiveness of Withaferin A in reducing the viability and migration of UTUC cells, suggesting potential for further clinical investigation.

Conclusions

The TBK1-associated oncogenic mechanism is prominent in UTUC patients with preexisting ESRD. Withaferin A demonstrates preclinical promise as a therapeutic candidate targeting this mechanism in UTUC patients with compromised renal function.

背景：上尿道尿路上皮癌是一种起源于泌尿道移行上皮的侵袭性恶性肿瘤。存在终末期肾病（ESRD）的UTUC患者由于双侧肾功能严重受损，围手术期治疗选择有限。因此，我们试图在这一患者群体中确定可靶向的致癌机制。方法：一项单中心回顾性研究分析了50例新鲜冷冻UTUC肿瘤样本（17例伴有ESRD， 33例未伴有ESRD），采用RNA测序进行转录组学分析。进行基因集富集分析以鉴定ESRD肿瘤中集体富集的基因集，并使用归一化富集评分（NES）来标准化不同大小集的富集程度。在UTUC诊断前进行定期血液透析以确定ESRD患者。免疫组织化学染色对石蜡包埋切片（6张带有ESRD， 7张没有）进行染色，以证明基因集中有代表性蛋白的参与。通过连通性图分析对候选药物进行排名，并通过体外细胞活力和迁移试验进一步评估抑制评分最高的药物。结果：由于两组之间的总生存率和癌症特异性生存率没有显著差异，我们将转录组差异解释为肿瘤固有特征，而不是疾病严重程度的后果。ESRD-UTUC患者中tbk1相关基因组富集（NES = 2.065， FDR q值= 0.001）。免疫组织化学证实ESRD组织中TBK1水平升高（P = 0.044）。IKK/NF-κB抑制剂Withaferin A （CAS No. 519 -48-2）成为主要候选药物（抑制评分= 2.521）。体外实验表明，Withaferin A可有效降低UTUC细胞的生存能力和迁移能力，为进一步的临床研究提供了可能。结论：tbk1相关的致癌机制在合并ESRD的UTUC患者中是突出的。Withaferin A作为针对这一机制的UTUC肾功能受损患者的临床前治疗候选药物，具有良好的前景。

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引用次数: 0

Stage Migration in Surgically Treated Renal Cell Carcinoma in México: A 44-Year Analysis of Survival Outcomes and Stage-Specific Prognostic Factors 手术治疗的肾细胞癌的分期转移：44年的生存结果和分期特异性预后因素分析

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-08-20 DOI: 10.1016/j.clgc.2025.102416

Jorge Augusto Alcacio-Mendoza, Horst Emanuel Lagos-Beitz, Petra Betsabé Carreño-Hinojosa, Yoztinn Bernal-Benitez, Guillermo H Martínez-Delgado, Ricardo A Castillejos-Molina, Francisco Rodriguez-Covarrubias

Background and objective

Renal cancer (RC) diagnosis has shifted toward earlier stages globally. However, this phenomenon and its impact on outcomes have not been characterized in Mexico. We aimed to analyze temporal trends in RC stage at diagnosis and assess their impact on survival rates.

Methods

We retrospectively analyzed 807 patients surgically treated (1980-2024), categorized by diagnosis decade. Median follow-up was 29.0 months (range: 0.0-298.4) calculated using reverse Kaplan-Meier method. We developed the Stage Migration Index (SMI) using weighted averages of stage proportions to quantify migration magnitude. Survival was analyzed using Kaplan-Meier curves and multilevel analysis evaluated hierarchical effects of decade and stage on outcomes.

Results

Stage I cases increased from 29.9% to 52.9%, while Stage III decreased from 31.9% to 13.4% (P < .001) and Stage IV from 10.6% to 6.7% (P = .317, nonsignificant). The SMI increased from 2.766 to 3.261, reflecting significant shift toward earlier stages (P < .001). Incidental detection increased from 44.7% (95% CI, 31.4%-58.8%) to 58.2% (95% CI, 49.7%-66.2%) (P < .001). Five-year survival improved from 85.7% (1980-1989) to 96.3% (2020-2024) (P < .001), though the 2020 to 2024 cohort had limited follow-up (median 1.4 months). Multilevel analysis revealed decade effects varied by stage, with greatest improvement for Stage IV patients (β = −0.542, P = .013). Among deceased patients, survival time increased from 5.2 to 50.2 months between 1980-1989 and 2010-2019 (P < .001). Limitations include retrospective single-center design, surgical cohort selection bias, and 12.5% missing survival data.

Conclusions

RC has undergone significant stage migration in Mexico over 4 decades. While this shift contributes to improved outcomes, our analysis demonstrates substantial survival gains across all stages, particularly in advanced disease, suggesting improvements in comprehensive RC management beyond earlier detection alone.

背景和目的在全球范围内，肾癌（RC）的诊断已经转向早期阶段。然而，这一现象及其对结果的影响在墨西哥并没有表现出来。我们的目的是分析诊断时RC阶段的时间趋势，并评估其对生存率的影响。方法回顾性分析1980 ~ 2024年807例手术治疗的患者，按诊断年代分类。中位随访时间为29.0个月（范围：0.0-298.4），采用反向Kaplan-Meier法计算。我们开发了阶段迁移指数（SMI），使用阶段比例的加权平均值来量化迁移幅度。生存率分析采用Kaplan-Meier曲线，多水平分析评估十年和分期对预后的分层效应。结果I期病例从29.9%上升到52.9%，III期病例从31.9%下降到13.4% (P < 0.001)， IV期病例从10.6%下降到6.7% （P = 0.317，无统计学意义）。SMI从2.766增加到3.261，反映了向早期阶段的显著转变（P < 0.001）。意外检出率从44.7% （95% CI, 31.4% ~ 58.8%）增加到58.2% (95% CI, 49.7% ~ 66.2%) （P < .001）。5年生存率从85.7%（1980-1989）提高到96.3% (2020-2024)(P < 0.001)，尽管2020-2024队列随访时间有限（中位1.4个月）。多水平分析显示，10年疗效因分期而异，IV期患者改善最大（β = - 0.542, P = 0.013）。在死亡患者中，1980-1989年和2010-2019年的生存时间从5.2个月增加到50.2个月（P < .001）。局限性包括回顾性单中心设计、手术队列选择偏倚和12.5%的生存数据缺失。结论40多年来，src在墨西哥发生了显著的阶段性迁移。虽然这一转变有助于改善预后，但我们的分析表明，在所有阶段，特别是晚期疾病中，生存率都有显著提高，这表明除了早期检测之外，还可以改善综合RC管理。

{"title":"Stage Migration in Surgically Treated Renal Cell Carcinoma in México: A 44-Year Analysis of Survival Outcomes and Stage-Specific Prognostic Factors","authors":"Jorge Augusto Alcacio-Mendoza, Horst Emanuel Lagos-Beitz, Petra Betsabé Carreño-Hinojosa, Yoztinn Bernal-Benitez, Guillermo H Martínez-Delgado, Ricardo A Castillejos-Molina, Francisco Rodriguez-Covarrubias","doi":"10.1016/j.clgc.2025.102416","DOIUrl":"10.1016/j.clgc.2025.102416","url":null,"abstract":"<div><h3>Background and objective</h3><div>Renal cancer (RC) diagnosis has shifted toward earlier stages globally. However, this phenomenon and its impact on outcomes have not been characterized in Mexico. We aimed to analyze temporal trends in RC stage at diagnosis and assess their impact on survival rates.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 807 patients surgically treated (1980-2024), categorized by diagnosis decade. Median follow-up was 29.0 months (range: 0.0-298.4) calculated using reverse Kaplan-Meier method. We developed the Stage Migration Index (SMI) using weighted averages of stage proportions to quantify migration magnitude. Survival was analyzed using Kaplan-Meier curves and multilevel analysis evaluated hierarchical effects of decade and stage on outcomes.</div></div><div><h3>Results</h3><div>Stage I cases increased from 29.9% to 52.9%, while Stage III decreased from 31.9% to 13.4% (<em>P</em> < .001) and Stage IV from 10.6% to 6.7% (<em>P</em> = .317, nonsignificant). The SMI increased from 2.766 to 3.261, reflecting significant shift toward earlier stages (<em>P</em> < .001). Incidental detection increased from 44.7% (95% CI, 31.4%-58.8%) to 58.2% (95% CI, 49.7%-66.2%) (<em>P</em> < .001). Five-year survival improved from 85.7% (1980-1989) to 96.3% (2020-2024) (<em>P</em> < .001), though the 2020 to 2024 cohort had limited follow-up (median 1.4 months). Multilevel analysis revealed decade effects varied by stage, with greatest improvement for Stage IV patients (β = −0.542, <em>P</em> = .013). Among deceased patients, survival time increased from 5.2 to 50.2 months between 1980-1989 and 2010-2019 (<em>P</em> < .001). Limitations include retrospective single-center design, surgical cohort selection bias, and 12.5% missing survival data.</div></div><div><h3>Conclusions</h3><div>RC has undergone significant stage migration in Mexico over 4 decades. While this shift contributes to improved outcomes, our analysis demonstrates substantial survival gains across all stages, particularly in advanced disease, suggesting improvements in comprehensive RC management beyond earlier detection alone.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102416"},"PeriodicalIF":2.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061229","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

Socioeconomic Disparities in Prostate Cancer Presentation: The Impact of ADI on Prostate Cancer Stage at Diagnosis 前列腺癌表现的社会经济差异：诊断时ADI对前列腺癌分期的影响。

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-08-19 DOI: 10.1016/j.clgc.2025.102418

Alessandro Bertini , Anna Tylecki , Alex Stephens , Alessio Finocchiaro , Silvia Viganò , Nicholas Cusmano , Arjun Dinesh , Elnaz Guivatchian , Giovanni Lughezzani , Nicolò Buffi , Ettore Di Trapani , Vincenzo Ficarra , Alberto Briganti , Andrea Salonia , Francesco Montorsi , Akshay Sood , Craig Rogers , Firas Abdollah

Objectives

To investigate the impact of socioeconomic deprivation, as measured by Area Deprivation Index (ADI), on PCa stage at diagnosis in a North-American statewide cohort.

Methods

The Michigan Department of Health and Human Services (MDHHS) was queried to identify men aged ≥30 with a confirmed diagnosis of PCa at prostate biopsy between 2004 and 2022. An ADI score was assigned to each patient based on their residential census block group. Individuals were further categorized into quartiles, where the fourth 1 (ADI 75-100) represented those living in the most deprived areas. Logistic regression analysis tested the impact of ADI on diagnosis with NCCN high-risk PCa (T3-T4 or PSA >20 ng/ml or ISUP GG ≥4) or metastatic PCa (N1 or M1) at presentation.

Results

We included 78018 patients, 17% of whom were Non-Hispanic Black (NHB). Median (IQR) age was 66 (59-72) years. Patients in the most disadvantage quartile (Q4) were more likely to be NHB (40.1% vs. 5.4%), had higher proportion with PSA>20 ng/ml (10.6 % vs. 5.1%), GG≥4 (55.4% vs. 53.1%), clinical T ≥ 3 (4% vs. 3%) and metastasis (3.3% vs. 1.8%) at diagnostic presentation, compared to those in the least disadvantaged quartile (Q1) (all P < .0001). At MVA, for each 10-unit increase in ADI percentile, the relative odds of being diagnosed with NCCN high-risk and metastatic PCa increases by 2% (95% CI, 1.01-1.02) and 4% (95% CI, 1.02-1.05), respectively. Moreover, when compared to NHW men, NHB men had a 1.16 (95% CI, 1.12-1.22) and a 1.52-fold (95% CI, 1.38-1.68) higher relative odds of being diagnosed with NCCN high-risk PCa and metastatic PCa, respectively (P < .001).

Conclusions

Living in more deprived areas was associated with higher relative odds of newly diagnosed PCa with unfavorable features. Our study underscores the silent barrier that socioeconomic deprivation poses to cancer early diagnosis and echo the call for tailored interventions to bridge this gap.

目的：调查社会经济剥夺的影响，作为衡量区域剥夺指数（ADI），在诊断前列腺癌阶段在北美全州队列。方法：对2004年至2022年间密歇根州卫生与公众服务部（MDHHS）年龄≥30岁、经前列腺活检确诊为前列腺癌的男性进行查询。根据每个患者居住的人口普查区分组对其进行ADI评分。个人被进一步划分为四分位数，其中第四个1 （ADI 75-100）代表生活在最贫困地区的人。Logistic回归分析检验了ADI对NCCN高危PCa （T3-T4或PSA >20 ng/ml或ISUP GG≥4）或转移性PCa （N1或M1）诊断的影响。结果：我们纳入78018例患者，其中17%为非西班牙裔黑人（NHB）。中位（IQR）年龄为66（59-72）岁。与最不利四分位数（Q1）的患者相比，最不利四分位数（Q4）的患者更容易出现NHB(40.1%比5.4%)，诊断时PSA bb0 20 ng/ml(10.6%比5.1%),GG≥4(55.4%比53.1%)，临床T≥3（4%比3%）和转移（3.3%比1.8%）的比例更高（均P < 0.0001）。在MVA， ADI百分位数每增加10个单位，诊断为NCCN高风险和转移性PCa的相对几率分别增加2% （95% CI, 1.01-1.02）和4% （95% CI, 1.02-1.05）。此外，与NHW男性相比，NHB男性被诊断为NCCN高危PCa和转移性PCa的相对几率分别高出1.16倍（95% CI, 1.12-1.22）和1.52倍（95% CI, 1.38-1.68）（P < 0.001）。结论：生活在更贫困的地区，新诊断的前列腺癌具有不利特征的相对几率更高。我们的研究强调了社会经济剥夺对癌症早期诊断造成的无声障碍，并呼应了对量身定制的干预措施的呼吁，以弥合这一差距。

{"title":"Socioeconomic Disparities in Prostate Cancer Presentation: The Impact of ADI on Prostate Cancer Stage at Diagnosis","authors":"Alessandro Bertini , Anna Tylecki , Alex Stephens , Alessio Finocchiaro , Silvia Viganò , Nicholas Cusmano , Arjun Dinesh , Elnaz Guivatchian , Giovanni Lughezzani , Nicolò Buffi , Ettore Di Trapani , Vincenzo Ficarra , Alberto Briganti , Andrea Salonia , Francesco Montorsi , Akshay Sood , Craig Rogers , Firas Abdollah","doi":"10.1016/j.clgc.2025.102418","DOIUrl":"10.1016/j.clgc.2025.102418","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the impact of socioeconomic deprivation, as measured by Area Deprivation Index (ADI), on PCa stage at diagnosis in a North-American statewide cohort.</div></div><div><h3>Methods</h3><div>The Michigan Department of Health and Human Services (MDHHS) was queried to identify men aged ≥30 with a confirmed diagnosis of PCa at prostate biopsy between 2004 and 2022. An ADI score was assigned to each patient based on their residential census block group. Individuals were further categorized into quartiles, where the fourth 1 (ADI 75-100) represented those living in the most deprived areas. Logistic regression analysis tested the impact of ADI on diagnosis with NCCN high-risk PCa (T3-T4 or PSA >20 ng/ml or ISUP GG ≥4) or metastatic PCa (N1 or M1) at presentation.</div></div><div><h3>Results</h3><div>We included 78018 patients, 17% of whom were Non-Hispanic Black (NHB). Median (IQR) age was 66 (59-72) years. Patients in the most disadvantage quartile (Q4) were more likely to be NHB (40.1% vs. 5.4%), had higher proportion with PSA>20 ng/ml (10.6 % vs. 5.1%), GG≥4 (55.4% vs. 53.1%), clinical <em>T</em> ≥ 3 (4% vs. 3%) and metastasis (3.3% vs. 1.8%) at diagnostic presentation, compared to those in the least disadvantaged quartile (Q1) (all <em>P</em> < .0001). At MVA, for each 10-unit increase in ADI percentile, the relative odds of being diagnosed with NCCN high-risk and metastatic PCa increases by 2% (95% CI, 1.01-1.02) and 4% (95% CI, 1.02-1.05), respectively. Moreover, when compared to NHW men, NHB men had a 1.16 (95% CI, 1.12-1.22) and a 1.52-fold (95% CI, 1.38-1.68) higher relative odds of being diagnosed with NCCN high-risk PCa and metastatic PCa, respectively (<em>P</em> < .001).</div></div><div><h3>Conclusions</h3><div>Living in more deprived areas was associated with higher relative odds of newly diagnosed PCa with unfavorable features. Our study underscores the silent barrier that socioeconomic deprivation poses to cancer early diagnosis and echo the call for tailored interventions to bridge this gap.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102418"},"PeriodicalIF":2.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082750","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

Association Between Early on-Treatment Weight Loss With Enfortumab Vedotin Plus Pembrolizumab and Survival in Advanced Urothelial Carcinoma 在晚期尿路上皮癌患者中，早期使用依福图单抗-维多汀联合派姆单抗治疗减肥与生存率的关系

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-08-17 DOI: 10.1016/j.clgc.2025.102417

Ryan D. Chow, Ronac Mamtani

Background

Combination therapy with enfortumab vedotin plus pembrolizumab (EV+P) is now the preferred first-line (1L) therapy for advanced urothelial carcinoma (aUC), but prognostic indicators for patients on 1L EV+P have not yet been described.

Patients and Methods

We conducted a retrospective cohort study of patients receiving 1L EV+P for aUC. We analyzed deidentified electronic health record data from the Flatiron Health database to identify adults with aUC who initiated EV+P between April 3, 2023 and December 31, 2024. Inclusion required absence of death, disease progression, or second line therapy start within 30 days of EV+P initiation, as well as documented weight measurements at the time of EV+P initiation (i.e., day 0) and day 28. We used Cox proportional hazards modeling with stabilized inverse probability treatment weighting (IPTW) to evaluate the association of early on-treatment weight loss with overall survival (OS), progression-free survival (PFS), and time to EV discontinuation.

Results

A total of 401 patients met study criteria. Of these, 78 patients (19.5%) experienced ≥ 5% weight loss by day 28 following EV+P initiation. Early on-treatment weight loss was associated with inferior OS (median 12.8 vs. 20.4 months; IPTW-adjusted HR [aHR] = 2.04 [1.41-2.95], P = 1.9 × 10^-4), but not with PFS (aHR = 1.22 [0.89-1.65], P = .22) or time to EV discontinuation (aHR = 1.30 [0.96-1.77], P = .090). The association of early on-treatment weight loss with OS was conserved in subgroup analyses stratifying patients by baseline albumin or BMI.

Conclusion

Early weight loss ≥5% occurred in one fifth of patients receiving 1L EV+P treatment and was associated with inferior overall survival.

背景：目前，对晚期尿路上皮癌（aUC）的首选一线（1L）治疗是用enfortumab vedotin + pembrolizumab （EV+P）联合治疗，但使用1L EV+P的患者的预后指标尚未被描述。患者和方法：我们对接受1L EV+P治疗aUC的患者进行了回顾性队列研究。我们分析了来自Flatiron health数据库的未识别电子健康记录数据，以识别在2023年4月3日至2024年12月31日期间开始使用EV+P的aUC成人。纳入要求在EV+P开始30天内没有死亡、疾病进展或开始二线治疗，以及在EV+P开始时（即第0天）和第28天记录的体重测量。我们使用具有稳定逆概率治疗加权（IPTW）的Cox比例风险模型来评估早期治疗体重减轻与总生存期（OS）、无进展生存期（PFS）和停药时间的关系。结果：共有401例患者符合研究标准。其中，78名患者（19.5%）在EV+P启动后第28天体重减轻≥5%。治疗早期体重减轻与较差的OS相关（中位12.8 vs. 20.4个月；经iptwr调整的HR [aHR] = 2.04 [1.41-2.95], P = 1.9 × 10-4），但与PFS （aHR = 1.22 [0.89-1.65], P = 0.22）或停药时间（aHR = 1.30 [0.96-1.77], P = 0.090）无关。在以基线白蛋白或BMI对患者进行分层的亚组分析中，早期治疗体重减轻与OS的关联是保守的。结论：接受1L EV+P治疗的患者中，早期体重减轻≥5%的患者占五分之一，且与总生存期较差相关。

{"title":"Association Between Early on-Treatment Weight Loss With Enfortumab Vedotin Plus Pembrolizumab and Survival in Advanced Urothelial Carcinoma","authors":"Ryan D. Chow, Ronac Mamtani","doi":"10.1016/j.clgc.2025.102417","DOIUrl":"10.1016/j.clgc.2025.102417","url":null,"abstract":"<div><h3>Background</h3><div>Combination therapy with enfortumab vedotin plus pembrolizumab (EV+P) is now the preferred first-line (1L) therapy for advanced urothelial carcinoma (aUC), but prognostic indicators for patients on 1L EV+P have not yet been described.</div></div><div><h3>Patients and Methods</h3><div>We conducted a retrospective cohort study of patients receiving 1L EV+P for aUC. We analyzed deidentified electronic health record data from the Flatiron Health database to identify adults with aUC who initiated EV+P between April 3, 2023 and December 31, 2024. Inclusion required absence of death, disease progression, or second line therapy start within 30 days of EV+<em>P</em> initiation, as well as documented weight measurements at the time of EV+P initiation (i.e., day 0) and day 28. We used Cox proportional hazards modeling with stabilized inverse probability treatment weighting (IPTW) to evaluate the association of early on-treatment weight loss with overall survival (OS), progression-free survival (PFS), and time to EV discontinuation.</div></div><div><h3>Results</h3><div>A total of 401 patients met study criteria. Of these, 78 patients (19.5%) experienced ≥ 5% weight loss by day 28 following EV+P initiation. Early on-treatment weight loss was associated with inferior OS (median 12.8 vs. 20.4 months; IPTW-adjusted HR [aHR] = 2.04 [1.41-2.95], <em>P</em> = 1.9 × 10<sup>-4</sup>), but not with PFS (aHR = 1.22 [0.89-1.65], <em>P</em> = .22) or time to EV discontinuation (aHR = 1.30 [0.96-1.77], <em>P</em> = .090). The association of early on-treatment weight loss with OS was conserved in subgroup analyses stratifying patients by baseline albumin or BMI.</div></div><div><h3>Conclusion</h3><div>Early weight loss ≥5% occurred in one fifth of patients receiving 1L EV+P treatment and was associated with inferior overall survival.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102417"},"PeriodicalIF":2.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017005","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

Penalized-Survival Nomogram Predicts 5-Year Metastasis-Free Survival After Salvage Radiotherapy for Postprostatectomy Patients: A Multicenter Study 前列腺切除术后患者补救性放疗后5年无转移生存的惩罚生存Nomogram预测：一项多中心研究

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2025-08-14 DOI: 10.1016/j.clgc.2025.102415

F. Mastroleo , R. Villa , M. Zaffaroni , M.G. Vincini , C. Franzese , L. Nicosia , F. Matrone , A. Donofrio , A. Magli , L. Triggiani , S. Barra , G. Timon , M. Augugliaro , V. Burgio , G. Francolini , M. Hasterok , M. Miszczyk , N. Simoni , C. Spatola , F. Alongi , B.A. Jereczek-Fossa

Background/Aim

Salvage radiotherapy (SRT) is a key treatment for biochemical recurrence (BCR) after radical prostatectomy (RP), yet a significant proportion of patients progress to distant metastasis. This multicenter retrospective study aimed to analyze a series of patients who underwent SRT and to develop a predictive nomogram for 5-year-distant-metastasis-free survival (DMFS).

Material and Methods

Data were collected from 15 European centers from June 1, 2022, to September 30, 2024. We included SRT patients due to BCR, following RP and no evidence of distant metastases on imaging. A penalized-survival nomogram was developed and internally validated; external validation was performed using data from the largest center. Patients were stratified into low-, intermediate-, and high-risk groups based on tertiles of the predicted risk score distribution.

Results

Data from 1,720 SRT patients were analyzed. BCR after SRT occurred in 620 (37%) patients, while clinical recurrence in 494 (30%) patients. Distant metastases were diagnosed in 228 patients (13%). The 2- and 5- years DMFS rates were 93% (95% CI, 92%-95%) and 84% (95% CI, 81%-86%), respectively. Multivariate analysis identified pT3/pT4 stage (HR 1.54 [95% CI, 1.13-2.13], P < .01), ISUP grade group 4/5 (HR 1.75 [95% CI, 1.30-2.35], P < .01), and SRT <12 months from surgery (HR 1.49 [95% CI, 1.07-2.09], P = .02) as independent predictors of DM. The nomogram achieved a C-index of 0.70 in external validation. Stratification into risk groups showed significant differences in DMFS (P < .01).

Conclusions

This externally validated nomogram provides a practical tool for predicting 5-year DMFS in patients undergoing SRT. It enables personalized risk assessment, guiding intensified surveillance and treatment for high-risk patients.

背景/目的：补救性放疗（SRT）是根治性前列腺切除术（RP）后生化复发（BCR）的关键治疗手段，但仍有相当比例的患者进展为远处转移。这项多中心回顾性研究旨在分析一系列接受SRT的患者，并制定5年无远处转移生存（DMFS）的预测图。材料和方法：数据收集于欧洲15个中心，时间为2022年6月1日至2024年9月30日。我们纳入了因BCR而进行SRT的患者，RP之后，影像学上没有远处转移的证据。开发并内部验证了惩罚生存nomogram；使用最大中心的数据进行外部验证。根据预测风险评分分布的位数，将患者分为低、中、高风险组。结果：分析了1,720例SRT患者的数据。SRT后BCR 620例（37%），临床复发494例（30%）。228例（13%）患者被诊断为远处转移。2年和5年DMFS率分别为93% （95% CI, 92%-95%）和84% （95% CI, 81%-86%）。多因素分析确定了pT3/pT4分期（HR 1.54 [95% CI, 1.13-2.13], P < 0.01）、ISUP分级4/5组（HR 1.75 [95% CI, 1.30-2.35], P < 0.01）和SRT。结论：这个外部验证的nomogram（图）为预测SRT患者5年DMFS提供了一个实用的工具。它可以实现个性化风险评估，指导加强对高危患者的监测和治疗。

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