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评估药物去势疗效的方法:一项系统评价

Methods for Evaluating the Efficacy of Medical Castration: A Systematic Review.

作者信息

Aguilar Adriana, Planas Jacques, Trilla Enrique, Morote Juan

机构信息

Department of Urology, Vall d'Hebron Hospital, 08035 Barcelona, Spain.

Department of Surgery, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

出版信息

Cancers (Basel). 2023 Jul 3;15(13):3479. doi: 10.3390/cancers15133479.

DOI:10.3390/cancers15133479
PMID:37444589
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10341338/
Abstract

Measuring serum testosterone determination during medical castration is recommended by prostate cancer (PCa) guidelines to assess its efficacy and define castration resistance. It has been suggested that other biochemical compounds, such as free testosterone or luteinising hormone (LH), could also assess castration efficacy. We aimed to analyse the current evidence for serum biochemical compounds that could be appropriate candidates for evaluating medical castration efficacy. A systematic review was conducted after two investigators independently searched the literature in the PubMed, Cochrane Library, and EMBASE databases published between January 1980 and February 2023. Their searches used the medical subject headings 'prostatic neoplasms', 'testosterone and androgen antagonists', 'gonadotropin-releasing hormone/analogues and derivatives', 'free testosterone', and 'luteinising hormone'. Studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, and their eligibility was based on the Participants, Intervention, Comparator, and Outcome strategy. The search was limited to original articles published in English. Among the 6599 initially identified titles, 15 original studies analysing the clinical impact of serum testosterone levels in PCa patients undergoing androgen deprivation therapy (ADT) were selected for evidence acquisition. The risk of bias in individual studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All selected studies used immunoassays to measure serum testosterone, although only methods based on liquid or gas chromatography and mass spectrometry are recommended to measure low testosterone concentrations. The reported series were not uniform in clinical stage, ADT types, and the time or number of serum testosterone measurements. Only some studies found low serum testosterone levels (<20 or <32 ng/dL) associated with greater survival free of biochemical progression and castration resistance. We conclude that little current evidence justifies the measurement of serum testosterone during ADT using no appropriate methods. No reported longitudinal studies have examined the clinical impact of serum testosterone measured using liquid chromatography with tandem mass spectrometry (LC-MSMS), free testosterone, or LH in PCa patients undergoing medical castration. We conclude that well-designed longitudinal studies examining the clinical impact of serum testosterone measured with LC-MSMS, serum-free testosterone, and LH on biochemical progression and castration resistance in PCa patients undergoing neo-adjuvant castration in radiation therapy or continuous castration are needed.

摘要

前列腺癌(PCa)指南建议在药物去势期间测量血清睾酮水平,以评估其疗效并确定去势抵抗。有人提出,其他生化化合物,如游离睾酮或促黄体生成素(LH),也可用于评估去势疗效。我们旨在分析目前关于血清生化化合物的证据,这些化合物可能是评估药物去势疗效的合适候选物。在两名研究人员独立检索1980年1月至2023年2月期间发表在PubMed、Cochrane图书馆和EMBASE数据库中的文献后,进行了一项系统综述。他们的检索使用了医学主题词“前列腺肿瘤”、“睾酮和雄激素拮抗剂”、“促性腺激素释放激素/类似物和衍生物”、“游离睾酮”和“促黄体生成素”。根据系统综述和Meta分析的首选报告项目标准选择研究,其纳入标准基于参与者、干预措施、对照和结局策略。检索仅限于以英文发表的原创文章。在最初确定的6599个标题中,选择了15项分析血清睾酮水平对接受雄激素剥夺治疗(ADT)的PCa患者临床影响的原创研究进行证据收集。使用诊断准确性研究质量评估2工具评估个别研究的偏倚风险。所有选定的研究均使用免疫测定法测量血清睾酮,尽管仅推荐基于液相或气相色谱和质谱法的方法来测量低睾酮浓度。报告的系列在临床分期、ADT类型以及血清睾酮测量的时间或次数方面并不统一。只有一些研究发现低血清睾酮水平(<20或<32 ng/dL)与更长的无生化进展生存期和去势抵抗相关。我们得出结论,目前几乎没有证据支持使用不合适的方法在ADT期间测量血清睾酮。没有报告的纵向研究考察了在接受药物去势的PCa患者中,使用液相色谱串联质谱法(LC-MSMS)测量的血清睾酮、游离睾酮或LH的临床影响。我们得出结论,需要进行精心设计的纵向研究,考察在接受放疗新辅助去势或持续去势的PCa患者中,用LC-MSMS测量的血清睾酮、游离睾酮和LH对生化进展和去势抵抗的临床影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5616/10341338/b919bd524de7/cancers-15-03479-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5616/10341338/8041b119ed70/cancers-15-03479-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5616/10341338/b919bd524de7/cancers-15-03479-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5616/10341338/8041b119ed70/cancers-15-03479-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5616/10341338/b919bd524de7/cancers-15-03479-g002.jpg

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A Phase I Clinical Trial Evaluating the Safety and Dosing of Relugolix with Novel Hormonal Therapy for the Treatment of Advanced Prostate Cancer.一项评估瑞戈非尼联合新型激素疗法治疗晚期前列腺癌的安全性和剂量的 I 期临床试验。
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