Clinical genitourinary cancer最新文献_第8页

Comments on PSMA use in the primary staging of prostate cancer 关于 PSMA 用于前列腺癌初级分期的评论。

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2024-10-23 DOI: 10.1016/j.clgc.2024.102246

Ryan P. Smith , Robert M. Turner , Ronald M. Benoit

引用次数: 0

Efficacy and Safety of Combination AKT and Androgen Receptor Signaling Inhibition in Metastatic Castration-Resistant Prostate Cancer: Systematic Review and Meta-Analysis 联合抑制 AKT 和雄激素受体信号转导治疗转移性抗性前列腺癌的有效性和安全性：系统回顾与元分析》。

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2024-10-19 DOI: 10.1016/j.clgc.2024.102244

Tulika A.K. Nahar , Maria Anna Bantounou , Isabella Savin , Nakul Chohan , Niraj S. Kumar , Aruni Ghose , Ian J. McEwan

Background

Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis with current treatment options including chemotherapy and androgen receptor signaling inhibitor (ARSI) medications. Poly-ADP ribose polymerase (PARP) inhibitors alone and in combination with ARSI has recently been incorporated in management for mCRPC deficient in BRCA1/2 genes. However, downregulating androgen-receptor signaling using ARSIs can upregulate the PI3K/AKT/mTOR pathway, promoting tumor cell survival. This creates a rationale for co-targeting both these pathways. This systematic review aimed to investigate AKT inhibitors and ARSI combination therapy.

Methods

EMBASE, MEDLINE, and Scopus were searched from database inception to July 2023. Primary outcomes included objective response rate (ORR), prostate-specific antigen (PSA) response rate, adverse events (AEs), overall survival (OS), and radiographic progression-free survival (rPFS). Quality was assessed using the risk of bias tool (ROB2) and certainty of evidence with GRADE.

Results

Six clinical trials with 3 Phase I, 1 Phase II, 1 Phase III were included with 771 patients and a median age ranging from 67 years to 70 years. The pooled ORR was 30% (n = 5 studies, 95% CI, 3%-84%) and PSA response rate was 43% (n = 5 studies, 95% CI, 15%-77%). The median duration of rPFS ranged from 8.2 to 19.2 months in the intervention compared with 6.4 to 16.6 months in the placebo group. A 16% reduction in radiographic progression or death was reported in patients receiving dual therapy compared with those receiving placebo. This reduction was greater by PTEN-loss status, ranging from 23% to 61%. The median OS ranged from 15.6 to 18.9 months. No significant difference was reported in survival relative to placebo. 98.8% (767/776) of patients experienced AEs of any grade, with GRADE ≥3 AEs occurring in 65.9% (512/776) of patients. The most common AE and GRADE ≥3 AEs were diarrhoea (pooled prevalence = 70%, 95% CI, 57%-81%), and hyperglycaemia (pooled prevalence = 12%, 95% CI, 6%-20%), respectively.

Conclusion

Combined therapy reduced the risk of rPFS, with the response higher in PTEN-loss subgroup, with a modest but not significant increase in OS. Our AE estimates showed consistency with other studies. AEs of any grade were common with the majority experiencing at least 1 AE. (PROSPERO Registration Number: CRD420202352583)

背景：转移性抗性前列腺癌（mCRPC）预后较差，目前的治疗方案包括化疗和雄激素受体信号抑制剂（ARSI）药物。聚ADP核糖聚合酶（PARP）抑制剂单独或与ARSI联合使用，最近已被纳入缺乏BRCA1/2基因的mCRPC的治疗方案。然而，使用ARSIs下调雄激素受体信号可上调PI3K/AKT/mTOR通路，促进肿瘤细胞存活。这就为同时针对这两种途径提供了理论依据。本系统综述旨在研究AKT抑制剂和ARSI联合疗法：方法：检索了从数据库开始到 2023 年 7 月的 EMBASE、MEDLINE 和 Scopus。主要结果包括客观反应率（ORR）、前列腺特异性抗原（PSA）反应率、不良事件（AE）、总生存期（OS）和无放射进展生存期（rPFS）。采用偏倚风险工具（ROB2）评估质量，采用GRADE评估证据的确定性：共纳入了六项临床试验，其中三项为一期临床试验，一项为二期临床试验，一项为三期临床试验，共有 771 名患者，中位年龄从 67 岁到 70 岁不等。汇总的ORR为30%（5项研究，95% CI，3%-84%），PSA反应率为43%（5项研究，95% CI，15%-77%）。干预组的 rPFS 中位持续时间为 8.2 至 19.2 个月，而安慰剂组为 6.4 至 16.6 个月。据报道，与接受安慰剂治疗的患者相比，接受双重疗法的患者的放射学进展或死亡减少了16%。PTEN缺失状态的降低幅度更大，从23%到61%不等。中位生存期从15.6个月到18.9个月不等。与安慰剂相比，生存期无明显差异。98.8%（767/776）的患者出现任何等级的AE，65.9%（512/776）的患者出现GRADE≥3的AE。最常见的AE和GRADE≥3 AE分别是腹泻（汇总发生率=70%，95% CI，57%-81%）和高血糖（汇总发生率=12%，95% CI，6%-20%）：联合治疗降低了rPFS风险，PTEN缺失亚组的反应较高，OS略有增加，但不显著。我们对AE的估计与其他研究一致。任何级别的AE都很常见，大多数人至少经历过1次AE。(PROSPERO注册号：CRD420202352583）。

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引用次数: 0

Safety Analysis of Co-Administration of Radiation Therapy with Enfortumab Vedotin Based Regimens in Metastatic Urothelial Carcinoma 转移性尿路上皮癌放疗与恩福单抗维多汀联合用药的安全性分析

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2024-10-18 DOI: 10.1016/j.clgc.2024.102243

S.N. Seyedin , G.K. Harada , E. Garemanian , D. Rafizadeh , D. Kaakour , S. Dwabe , A. Rezazadeh , M. Daneshvar , N. Mar

Introduction/Background

Enfortumab vedotin (EV) and pembrolizumab (P) is the standard of care for patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Because radiation (RT) is frequently used for symptom palliation, we examined the safety of co-administering EV with RT.

Materials and Methods

This single institution retrospective study selected patients with la/mUC, who received at least 1 dose of EV and initiated RT to any site within 30 days of each other. Patient characteristics, number of EV cycles received, the location of irradiated sites, RT dose/delivery approach, severity/type of radiation treatment-related adverse events (TRAEs), and symptom response after RT were recorded. The primary aim of this study was to examine radiation TRAEs, with severity graded using the CTCAE version 5.0 classification.

Results

Nine patients with 15 irradiated metastasis met eligibility criteria. The median radiation dose and cycles of EV were 30 Gy and 5 cycles respectively. Patients only experienced acute grade 1 or 2 TRAEs including fatigue, nausea, and dermatitis without desquamation. Chronic treatment-related toxicity was noted in 2 patients, which were grade 1 neck pain and 2 fatigue. All patients demonstrated some degree of symptom relief and four experienced complete resolution of their cancer-related symptoms at the irradiated site. One patient with limited disease burden completed stereotactic body radiation therapy and remains disease free 6 months after discontinuing all treatment.

Conclusion

This study demonstrates that co-administration of RT with EV-based regimens could be safe and effective for symptom palliation. Larger series examining this treatment combination are needed.

简介/背景：恩福单抗韦多汀（EV）和pembrolizumab（P）是治疗局部晚期或转移性尿路上皮癌（la/mUC）患者的标准疗法。由于放射治疗（RT）经常用于缓解症状，我们研究了EV与RT联合用药的安全性：这项单机构回顾性研究选择了至少接受过一次EV治疗并在30天内在任何部位开始接受RT治疗的la/mUC患者。研究记录了患者特征、接受EV治疗的周期数、照射部位的位置、RT剂量/给药方式、放射治疗相关不良事件（TRAEs）的严重程度/类型以及RT后的症状反应。本研究的主要目的是检查放射治疗相关不良事件，并采用 CTCAE 5.0 版进行严重程度分级：结果：9名患者的15处照射转移灶符合标准。EV的中位放射剂量和周期分别为30 Gy和5个周期。患者仅出现急性1级或2级TRAE，包括疲劳、恶心和无脱屑皮炎。有 2 名患者出现了慢性治疗相关毒性反应，分别是 1 级颈部疼痛和 2 级疲劳。所有患者的症状都得到了一定程度的缓解，4 名患者的照射部位癌症相关症状完全消失。一名疾病负担有限的患者完成了立体定向体放射治疗，并在停止所有治疗 6 个月后仍未患病：这项研究表明，联合应用 RT 和以 EV 为基础的治疗方案可以安全有效地缓解症状。需要对这种治疗组合进行更大规模的系列研究。

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引用次数: 0

Landscape of Genomic Profiling and Circulating Tumor DNA Among Rare Genitourinary Cancers 罕见泌尿生殖系统癌症中基因组图谱和循环肿瘤 DNA 的分布情况

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2024-10-18 DOI: 10.1016/j.clgc.2024.102245

Austin G Kazarian, Raj R Bhanvadia, Zine-Eddine Khene, Thomas Gerald, Bailey Brooks, Yair Lotan, Isamu Tachibana, Kris Gaston, Sol Woldu, Vitaly Margulis

•
Current surveillance and treatment strategies of rare genitourinary cancers are heterogenous and often rely on classical imaging alone leaving opportunity for enhanced surveillance and treatment direction strategies.
•
Molecular residual disease assessment may offer many benefits to standard modalities including antecedent prediction of recurrence or progression compared to conventional surveillance, early and appropriate identification of patients appropriate for adjuvant treatment, potential for monitoring of treatment response, and adjudication of indeterminate imaging findings.
•
Comprehensive genomic profiling delineates tumor biology and actionable mutations for personalized medicine in this challenging to treat population including nonclassical targeted agents.

-目前对罕见泌尿生殖系统癌症的监控和治疗策略各不相同，而且通常仅依赖于传统的成像技术，这为加强监控和治疗指导策略留下了机会。-分子残留疾病评估可为标准模式带来许多益处，包括与传统监测相比，可对复发或病情进展进行先期预测、早期适当识别适合辅助治疗的患者、监测治疗反应的潜力以及对不确定的成像结果进行判定。

引用次数: 0

Detection of Apical Cancer with Novel Imaging Modalities to Predict Apical Margin Positivity in Robotic Assisted Radical Prostatectomy 在机器人辅助根治性前列腺切除术中，利用新型成像模式检测根尖癌，预测根尖边缘阳性率。

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2024-10-18 DOI: 10.1016/j.clgc.2024.102240

Vinayak G. Wagaskar, Ashutosh Maheshwari, Osama Zaytoun, Yashaswini Agarwal, Neeraja Tillu, Asher Mandel, Ash Tewari

Objectives

To evaluate margin positivity at apex utilizing preoperative magnetic resonance imaging [MRI], micro-ultrasound [MUS], prostate specific membrane antigen positron emission tomography PSMA PET] scan, biopsy location and intraoperative timing of deep venous complex [DVC] ligation during robot assisted radical prostatectomy [RARP].

Methods

Institution review board approved retrospective study underwent RARP between November 2022 to March 2024. All patients underwent preoperative MRI, MUS and PSMA PET scan. Patients underwent RARP using either standard DVC [done prior apical dissection] ligation or delayed DVC [after prostate removal] technique. All patients underwent intra operative frozen section analysis by an experienced genitourinary pathologist. Descriptive statistics were performed. Data analyzed using R software version 4.3.3.

Results

Total 619 prostate cancer patients underwent RARP. Of these, 365 men underwent RARP using delayed DVC ligation technique and 254 men using standard DVC ligation technique. There was no statically significant difference in 2 groups on demographic parameters, MRI, MUS and PSMA-PET scan features. Sensitivity of MRI, MUS, PSMA-PET and prostate biopsy for detection of apical positive margin were 66%, 81%, 81% and 73% respectively. Specificity of MRI, MUS, PSMA-PET and prostate biopsy for detection of apical positive margin were 45%, 14%, 16% and 30% respectively. When all modalities are used accumulatively, apical cancer was missed only in 1% of cases.

Conclusions

With proper preoperative understanding of apical lesion location, timing of DVC ligation [standard vs delayed] doesn't impact apical positive surgical margins. Combination of MRI, MUS, PSMA-PET and prostate biopsy reduce apical positive surgical margin rates significantly.

目的利用术前磁共振成像[MRI]、显微超声[MUS]、前列腺特异性膜抗原正电子发射断层扫描[PSMA PET]扫描、活检位置以及机器人辅助前列腺癌根治术[RARP]中深部静脉复合体[DVC]结扎的术中时机，评估顶端边缘阳性率：方法：2022 年 11 月至 2024 年 3 月期间，经机构审查委员会批准，对接受机器人辅助前列腺癌根治术（RARP）的患者进行回顾性研究。所有患者均接受了术前 MRI、MUS 和 PSMA PET 扫描。患者采用标准 DVC（先行根尖切除术）结扎术或延迟 DVC（前列腺切除术后）技术进行 RARP。所有患者均由经验丰富的泌尿生殖系统病理学家进行术中冰冻切片分析。进行了描述性统计。使用 R 软件 4.3.3 版分析数据：共有 619 名前列腺癌患者接受了 RARP 治疗。其中，365 名男性采用延迟 DVC 结扎技术进行了 RARP，254 名男性采用标准 DVC 结扎技术进行了 RARP。两组患者在人口统计学参数、MRI、MUS 和 PSMA-PET 扫描特征方面无明显差异。磁共振成像、MUS、PSMA-PET 和前列腺活组织检查发现顶端阳性边缘的敏感性分别为 66%、81%、81% 和 73%。核磁共振成像、MUS、PSMA-PET 和前列腺活组织检查发现顶端阳性边缘的特异性分别为 45%、14%、16% 和 30%。如果将所有方法综合使用，仅有1%的病例漏诊了根尖癌：结论：在术前正确理解根尖病灶位置的情况下，DVC结扎的时机（标准与延迟）不会影响根尖阳性手术切缘。MRI、MUS、PSMA-PET和前列腺活组织检查相结合可显著降低根尖手术切缘阳性率。

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引用次数: 0

Doxorubicin, Paclitaxel, and Cisplatin (ATP) for Relapsed/Refractory Germ Cell Tumors 多柔比星、紫杉醇和顺铂（ATP）治疗复发/难治生殖细胞肿瘤。

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2024-10-18 DOI: 10.1016/j.clgc.2024.102242

Jenny J Xiang , Matthew T Campbell , Shi-Ming Tu , John Araujo , Yago Nieto , John K Lin , Lianchun Xiao , Amishi Y Shah , Jianbo Wang

Patients with relapsed/refractory germ cell tumors (GCT) have limited treatment options and poor survival outcomes. We describe our institutional experience with doxorubicin, paclitaxel, and cisplatin (ATP) as an outpatient regimen for 35 patients with relapsed/refractory GCT between 2017 and 2022. Twenty-four patients received nonpalliative intent ATP, with a median of 2 lines of prior therapy, 23 (96%) having received at least 1 cisplatin-based regimen and 1 (4%) with a prior stem cell transplant. The objective response rate for the nonpalliative intent cohort was 37.5% (1 complete response and 8 partial responses). Post-ATP, 12 patients underwent stem cell transplant, 7 patients had surgical resections, and 4 patients received radiation. The median PFS was 4.3 months (95% CI: 3.8, 32.7) and median OS of 13.1 months (95% CI: 10.7, NA) for the nonpalliative intent cohort. Eleven patients received palliative intent ATP, with a median of 4 lines of prior therapy, all having received at least 1 cisplatin-based regimen, and 7 (64%) having received prior stem cell transplants. Within the palliative intent cohort, the objective response rate was 9% (1 partial response). Patients who received palliative intent ATP had a median PFS of 0.92 months (95% CI 0.46, NA) and median OS of 5.2 months (95% CI 3.3, NA). Treatment toxicities occurred in 5 (14%) patients who required dose reductions and 5 (14%) patients who were admitted for treatment related toxicities, most commonly for myelosuppression. Our results support the use of ATP in a primarily anthracycline naïve patient population and show the safety of continued cisplatin use in patients who have previously received cisplatin-based regimens. Therefore, ATP is a feasible and well tolerated chemotherapy regimen in the salvage setting and can serve as a bridge to other treatments for patients with relapsed/refractory GCT.

复发/难治性生殖细胞瘤（GCT）患者的治疗方案有限，生存率较低。我们介绍了本机构在2017年至2022年间采用多柔比星、紫杉醇和顺铂（ATP）作为门诊治疗方案治疗35名复发/难治性GCT患者的经验。24名患者接受了非姑息性ATP治疗，既往治疗中位数为2种，其中23人（96%）至少接受过1种顺铂治疗，1人（4%）既往接受过干细胞移植。非姑息治疗组的客观反应率为37.5%（1例完全反应和8例部分反应）。ATP后，12名患者进行了干细胞移植，7名患者进行了手术切除，4名患者接受了放射治疗。非姑息治疗队列的中位PFS为4.3个月（95% CI：3.8，32.7），中位OS为13.1个月（95% CI：10.7，NA）。11名患者接受了姑息性ATP治疗，中位数为4种既往治疗方案，均接受过至少一种顺铂治疗方案，7名患者（64%）接受过干细胞移植。在姑息治疗队列中，客观反应率为9%（1例部分反应）。接受姑息治疗ATP的患者中位PFS为0.92个月（95% CI为0.46，不详），中位OS为5.2个月（95% CI为3.3，不详）。5例（14%）患者出现治疗毒性反应，需要减少剂量，5例（14%）患者因治疗相关毒性反应入院，最常见的是骨髓抑制。我们的研究结果支持在主要使用蒽环类药物的新患者群体中使用 ATP，并表明在既往接受过顺铂治疗的患者中继续使用顺铂是安全的。因此，ATP是一种可行且耐受性良好的挽救性化疗方案，可作为复发/难治性GCT患者通往其他治疗的桥梁。

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引用次数: 0

Risk of Metachronous Upper Tract Urothelial Carcinoma After Ureteral Stenting in Patients With Bladder Cancer 膀胱癌患者接受输尿管支架术后并发上尿路上皮癌的风险

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2024-10-17 DOI: 10.1016/j.clgc.2024.102241

Pietro Scilipoti , Marco Moschini , Mario de Angelis , Mattia Longoni , Luca Afferi , Chiara Lonati , Paolo Zaurito , Renate Pichler , Andrea Necchi , Francesco Montorsi , Alberto Briganti , Andrea Mari , Wojciech Krajewski , Ekaterina Laukthina , Benjamin Pradere , Francesco Del Giudice , Laura Mertens , Andrea Gallioli , Francesco Soria , Paolo Gontero , Roberto Carando

Objective

Sparse data exist on the impact of upper urinary tract (UUT) decompression on the risk of UUT recurrence in patients with bladder cancer (BCa). This study aims to evaluate whether Double J stenting (DJS) can increase the risk of UUT recurrence compared to percutaneous nephrostomy (PCN) placement.

Materials and methods

We retrospectively analyzed data from 1550 patients with cTa-T3NanyM0 BCa who underwent radical cystectomy (RC) between at 12 tertiary care centers (1990-2020). Patients with complete follow-up, no prior history of UUT cancer, and who required UUT decompression for preoperative hydronephrosis were selected. Hydronephrosis grade was defined according to established scoring systems. UUT recurrence was diagnosed through imaging, urinary cytology, and confirmed by selective cytology and ureteroscopy when possible. Propensity scores were computed to determine overlap weights and balance groups. Kaplan–Meier analyses estimated UUT recurrence-free survival (RFS), cancer-specific (CSS), and overall survival (OS) before and after weighting. Cox regression analyses before and after weighting were fitted to predict UUT recurrence.

Results

Of 524 included patients, 132 (25%) and 392 (75%) patients were managed with DJS and PCN placement, respectively. Patients who received PCN had higher grade (≥ 3) of obstruction (34% vs. 14%) and pT3-4 tumors (70% vs. 36%) than patients with DJS. During a median follow-up of 19 months, 2-years UUT-RFS did not differ between groups (95% for PCN vs 92% for DJS, weighted HR 1.41, 95% CI, 0.55-3.59). There was no difference in 2-years weighted CSS (74% vs. 74%) and OS (67% vs 69%). Main limitations were the short follow-up and inclusion of patients uniquely undergoing RC.

Conclusions

These results suggest that ureteral DJS does not increase the risk of developing UUT recurrence in BCa patients with hydronephrosis requiring UUT decompression. However, UUT recurrence was rare, and associations were weak, with findings susceptible to bias. Randomized trials are needed to validate these results.

目的关于上尿路（UUT）减压对膀胱癌（BCa）患者 UUT 复发风险的影响的数据很少。本研究旨在评估与经皮肾造瘘术（PCN）相比，双 J 支架置入术（DJS）是否会增加 UUT 复发的风险。材料与方法我们回顾性分析了 12 家三级医疗中心（1990-2020 年）中接受根治性膀胱切除术（RC）的 1550 例 cTa-T3NanyM0 BCa 患者的数据。这些患者均接受过完整的随访，既往无 UUT 癌症史，且术前因肾积水而需要进行 UUT 减压术。肾积水等级根据已建立的评分系统进行定义。UUT 复发通过影像学和尿液细胞学诊断，并在可能的情况下通过选择性细胞学和输尿管镜检查确认。计算倾向评分以确定重叠权重和平衡组别。Kaplan-Meier分析估计了加权前后的UUT无复发生存期（RFS）、癌症特异性生存期（CSS）和总生存期（OS）。结果在纳入的 524 例患者中，分别有 132 例（25%）和 392 例（75%）患者接受了 DJS 和 PCN 治疗。与接受DJS治疗的患者相比，接受PCN治疗的患者梗阻等级（≥3）（34%对14%）和pT3-4肿瘤（70%对36%）更高。在中位 19 个月的随访期间，两组患者的 2 年 UUT-RFS 无差异（PCN 为 95% vs DJS 为 92%，加权 HR 1.41，95% CI，0.55-3.59）。2年加权CSS（74% vs. 74%）和OS（67% vs. 69%）没有差异。结论这些结果表明，输尿管 DJS 不会增加需要进行 UUT 减压术的 BCa 肾积水患者 UUT 复发的风险。但是，UUT 复发很少见，而且相关性很弱，研究结果容易出现偏差。需要进行随机试验来验证这些结果。

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引用次数: 0

The Impact of Concomitant Medications on the Overall Survival of Patients Treated with Systemic Therapy for Advanced or Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-analysis 并用药物对晚期或转移性肾细胞癌全身疗法患者总生存期的影响：系统回顾与 Meta 分析》（The Impact of Concomitant Medications on Overall Survival of Patients Treated with Systemic Therapy for Advanced or Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-analysis.

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2024-10-17 DOI: 10.1016/j.clgc.2024.102237

Ichiro Tsuboi , Akihiro Matsukawa , Mehdi Kardoust Parizi , Marcin Miszczyk , Tamás Fazekas , Robert J. Schulz , Stefano Mancon , Giulio Litterio , Ekaterina Laukhtina , Tatsushi Kawada , Satoshi Katayama , Takehiro Iwata , Kensuke Bekku , Pawel Rajwa , Koichiro Wada , Pierre I. Karakiewicz , Motoo Araki , Shahrokh F. Shariat

Although immune checkpoint inhibitors (ICI) and/or tyrosine kinase inhibitors (TKI) are the standard treatment of advanced unresectable or metastatic renal cell carcinoma (RCC), the impact of concomitant medications remains unclear. We aimed to evaluate the impact of concomitant medications on survival outcomes in patients treated with systemic therapy for advanced unresectable or metastatic RCC. In August 2024, PubMed, Scopus, and Web of Science were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic RCC (PROSPERO: CRD42024573252). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis according to heterogeneity. We identified 22 eligible studies (5 prospective and 17 retrospective) comprising 16,072 patients. Concomitant medications included proton pump inhibitors (PPI) (n = 3959), antibiotics (n = 571), statins (n = 5466), renin-angiotensin system inhibitors (RASi) (n = 6615), and beta-blockers (n = 1964). Both concomitant PPI and antibiotics were significantly associated with worse OS in patients treated with ICI (PPI: HR: 1.22, P = .01, and antibiotics: HR: 2.09, P < .001). Concomitant statins, RASi, or beta-blocker were significantly associated with improved OS in patients treated with TKI (statins: HR: 0.81, P = .03, RASi: HR: 0.63, P < .001, beta-blocker: HR: 0.69, P < .001, respectively). In patients treated with ICI, RASi was significantly associated with improved OS (HR: 0.64, P = .02). Concomitant use of antibiotics or PPI with ICI can reduce its oncologic efficacy. Conversely, concomitant statins, RASi, or beta-blockers can enhance the oncologic efficacy of TKI. When initiating systemic therapy for metastatic RCC, it may be important for clinicians to assess baseline co-medications and recognize their possible positive or negative effects.

尽管免疫检查点抑制剂（ICI）和/或酪氨酸激酶抑制剂（TKI）是晚期不可切除或转移性肾细胞癌（RCC）的标准治疗方法，但伴随药物的影响仍不明确。我们旨在评估并用药物对接受全身治疗的晚期不可切除或转移性RCC患者生存结果的影响。2024年8月，我们在PubMed、Scopus和Web of Science上查询了评估晚期不可切除或转移性RCC患者伴随用药的研究（PROSPERO：CRD42024573252）。主要结果是总生存期（OS）。根据异质性采用固定效应或随机效应模型进行荟萃分析。我们确定了 22 项符合条件的研究（5 项前瞻性研究和 17 项回顾性研究），包括 16,072 名患者。同时服用的药物包括质子泵抑制剂（PPI）（n = 3959）、抗生素（n = 571）、他汀类药物（n = 5466）、肾素-血管紧张素系统抑制剂（RASi）（n = 6615）和β-受体阻滞剂（n = 1964）。在接受 ICI 治疗的患者中，同时服用 PPI 和抗生素与较差的 OS 显著相关（PPI：HR：1.22，P = .01；抗生素：HR：2.09，P < .001）。同时服用他汀类药物、RASi 或 β-受体阻滞剂与 TKI 治疗患者的 OS 改善显著相关（他汀类药物：HR：0.81，P = 0.01，抗生素：HR：2.09，P < 0.001）：HR：0.81，P = .03；RASi：HR：0.63，P < .001；β-受体阻滞剂：HR：0.69，P < .001）。在接受 ICI 治疗的患者中，RASi 与 OS 的改善显著相关（HR：0.64，P = .02）。ICI 同时使用抗生素或 PPI 会降低其肿瘤疗效。相反，同时使用他汀类药物、RASi 或 β-受体阻滞剂可提高 TKI 的肿瘤疗效。在开始对转移性 RCC 进行全身治疗时，临床医生必须评估基线联合用药，并认识到它们可能产生的积极或消极影响。

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引用次数: 0

Avelumab First-Line Maintenance for Locally Advanced or Metastatic Urothelial Carcinoma: Results From the Real-World US PATRIOT-II Study 阿维单抗一线维持治疗局部晚期或转移性尿路上皮癌：美国 PATRIOT-II 真实世界研究结果。

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2024-10-17 DOI: 10.1016/j.clgc.2024.102238

Petros Grivas , Pedro Barata , Helen Moon , Shilpa Gupta , Thomas Hutson , Cora N. Sternberg , Jason R. Brown , Vaidehi Dave , Chad Downey , Alicia C. Shillington , Howard M. Katzenstein , Melissa Kirker , Sarah Hanson , Frank X. Liu , Valerie Morris , Abhijeet Bhanegaonkar , Guru P. Sonpavde

Introduction

In JAVELIN Bladder 100, avelumab first-line maintenance (1LM) improved overall survival (OS) and progression-free survival (PFS) in patients with locally advanced/metastatic urothelial carcinoma (la/mUC) without progression following 1L platinum-based chemotherapy (PBC) versus best supportive care. PATRIOT-II describes real-world outcomes with avelumab 1LM.

Patients and Methods

This observational, retrospective study of avelumab 1LM in US community/academic centers used medical record data collected from avelumab initiation for ≥12 months to assess survival, safety, and healthcare resource utilization; analyses are descriptive.

Results

The study included 160 patients from 37 centers (median age, 70 years; 77% male). Avelumab 1LM was initiated at a median of 4 weeks (IQR 3-6) after PBC completion. Median follow-up from avelumab 1LM was 16 months (IQR 11-21). At study end, 19.4% of patients continued avelumab; 73.7% had discontinued due to progression, adverse events (AEs), or performance status deterioration. Median PFS and OS from avelumab initiation were 5.4 months (95% CI, 3.8-6.9) and 24.4 months (95% CI, 20.4-28.4), respectively. Grade ≥3 treatment-related AEs (TRAEs) occurred in 15 patients (9.4%); 35 (21.9%) had any-grade immune-related AEs, and 23 (14.3%) received high-dose systemic corticosteroids for AEs. Forty-four patients (27.5%) were hospitalized during the avelumab treatment period, of whom 13 (8.1%) were hospitalized due to TRAEs. Limitations of this study include a small sample size, potential selection bias, and missing/unknown data.

Conclusion

These results align with the JAVELIN Bladder 100 clinical trial and other real-world studies, supporting avelumab 1LM use in patients with la/mUC without progression following 1L PBC.

简介在JAVELIN Bladder 100研究中，阿维列单抗一线维持治疗（1LM）与最佳支持治疗相比，提高了局部晚期/转移性尿路上皮癌（la/mUC）患者的总生存期（OS）和无进展生存期（PFS）。PATRIOT-II描述了阿维列单抗1LM的实际疗效：这项在美国社区/学术中心进行的阿维列单抗1LM观察性、回顾性研究使用了从阿维列单抗开始治疗≥12个月时收集的病历数据，以评估生存率、安全性和医疗资源利用率；分析为描述性分析：研究纳入了来自 37 个中心的 160 名患者（中位年龄 70 岁；77% 为男性）。阿维列单抗 1LM 在 PBC 结束后中位 4 周（IQR 3-6）时启动。阿维列单抗1LM的中位随访时间为16个月（IQR为11-21）。研究结束时，19.4%的患者继续使用阿维单抗；73.7%的患者因病情进展、不良事件（AE）或表现状态恶化而停药。从开始使用阿维鲁单抗起，中位PFS和OS分别为5.4个月（95% CI，3.8-6.9）和24.4个月（95% CI，20.4-28.4）。15名患者（9.4%）出现了≥3级治疗相关AEs（TRAEs）；35名患者（21.9%）出现了任何级别的免疫相关AEs，23名患者（14.3%）因AEs接受了大剂量全身皮质类固醇治疗。44名患者（27.5%）在阿维鲁单抗治疗期间住院，其中13名患者（8.1%）因TRAE住院。本研究的局限性包括样本量较小、潜在的选择偏倚以及数据缺失/未知：这些结果与JAVELIN Bladder 100临床试验及其他实际研究结果一致，支持阿维列单抗1LM用于1L PBC后无进展的la/mUC患者。

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引用次数: 0

NODESAFE Nomogram: A Novel Score System to Predict Lymph Node Involvement at the Time of Nephrectomy or Nodal Recurrence in Nonmetastatic Renal Cell Carcinoma NODESAFE Nomogram：预测非转移性肾细胞癌肾切除术时淋巴结受累或结节复发的新评分系统

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer

Pub Date : 2024-10-11 DOI: 10.1016/j.clgc.2024.102232

Cesare Saitta , Giuseppe Garofano , Jonathan A. Afari , Hajime Tanaka , Dattatraya Patil , Kit L. Yuen , Luke Wang , Julian Cortes , Margaret F. Meagher , Dhruv Puri , Clara Cerrato , Mimi V. Nguyen , Kevin Hakimi , Masaki Kobayashi , Shohei Fukuda , Marco Paciotti , Massimo Lazzeri , Giovanni Lughezzani , Nicolò M. Buffi , Yasuhisa Fujii , Ithaar H. Derweesh

Objective

We sought to develop a preoperative nomogram called NODESAFE (NODE SAFEty) to predict nodal involvement (NI) at time of surgery or subsequent follow up in localized renal cell carcinoma (RCC), as the role of lymphadenectomy in localized RCC remains controversial.

Methods

We conducted a multicenter retrospective analysis of RCC patients who underwent primary surgical resection. Patients with clinical metastasis at presentation were excluded. NI was defined as presence of histological RCC with lymphadenectomy at time of surgery, or subsequent development histologically proven NI. The dataset was divided into training (70%) and testing subsets to facilitate model evaluation which was constructed through a stepwise multivariable logistic regression (MLR) model. Accuracy was tested with receiver operator characteristic estimated area under the curve (AUC).

Results

Total 3308 patients (2221 [67.1%] male) met inclusion criteria. During follow-up 25 patients (0.76 %) experienced nodal recurrence, and 22/25 were preoperatively classified as cN0. In our cohort, 112 (3.4%) patients had clinical lymphadenopathy preoperatively (cN1), and 34/112 were pN1. The following covariates were found to be statically significant on a MLR model: hypertension (Odds ratio [OR] 3.35, < .001), Charlson Comorbidity Index ≥ 5 (OR 1.93 P = .025), tumor size ≥ 6 cm (OR 2.63, P = .001), tumor necrosis at CT scan (OR 1.83, P = .036), cN1 (OR 5.59, P < .001) and CRP ≥ 8.5 mg/L (1.96, P = .018). Testing the prediction performance of the model in the validation set AUC of the model was 0.89. NODESAFE demonstrated a sensitivity of 83.9%, specificity of 86.1% and 99.1% negative predictive values using a 4% threshold probability.

Conclusion

Combining clinical features, serum biomarkers and radiographic findings, we developed a model capable of predicting NI with high degree of accuracy. NODESAFE may refine clinical decision making with respect to the performance of lymphadenectomy at the time of surgery, postsurgical surveillance, and spur consideration for adjuvant therapy.

目的我们试图开发一种名为NODESAFE（NODE SAFEty）的术前提名图，用于预测局部肾细胞癌（RCC）手术或后续随访时的结节受累（NI）情况，因为淋巴结切除术在局部RCC中的作用仍存在争议。方法我们对接受初次手术切除的RCC患者进行了一项多中心回顾性分析。我们对接受初次手术切除的 RCC 患者进行了多中心回顾性分析。NI的定义是手术时存在组织学意义上的RCC并进行了淋巴结切除术，或随后出现组织学意义上的NI。数据集被分为训练子集（70%）和测试子集，以便于通过逐步式多变量逻辑回归（MLR）模型进行模型评估。结果共有 3308 例患者（2221 例[67.1%]男性）符合纳入标准。随访期间，25 名患者（0.76%）出现结节复发，22/25 在术前被归类为 cN0。在我们的队列中，112 例（3.4%）患者术前有临床淋巴结病（cN1），34/112 例为 pN1。以下协变量在 MLR 模型中具有统计学意义：高血压（Odds ratio [OR] 3.35，< .001）、Charlson 综合征指数≥ 5（OR 1.93 P = .025）、肿瘤大小≥ 6 cm（OR 2.63，P = .001）、CT 扫描时肿瘤坏死（OR 1.83，P = .036）、cN1（OR 5.59，P <.001）和 CRP ≥ 8.5 mg/L（1.96，P = .018）。在验证集测试模型的预测性能时，模型的 AUC 为 0.89。NODESAFE 的灵敏度为 83.9%，特异性为 86.1%，以 4% 的阈值概率计算，阴性预测值为 99.1%。NODESAFE 可以完善临床决策，包括手术时的淋巴腺切除、术后监测以及辅助治疗的考虑。

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引用次数: 0