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《柳叶刀》(The Lancet)发表一项基于个体患者数据的meta分析,旨在探讨根治性前列腺切除术后,辅助放疗联合激素治疗能否改善患者总生存期,并明确不同激素治疗时长及术前PSA水平对疗效的影响。本研究提供了迄今为止最高级别证据,对于术前PSA≤0.5ng/mL的患者,在术后放疗基础上增加短期或长期激素治疗,均未观察到具有临床意义的总生存期获益,并且短期与长期激素治疗之间的疗效也无明显差异识别文中二维码或点击文末“阅读原文”,查阅原文。

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复发性前列腺癌术后放疗联合激素治疗的效果及用药时长的影响:一项个体患者数据meta分析

背景

在局限性前列腺癌的根治性放疗中,加入激素治疗可改善总生存期,但在根治性前列腺切除术后行术后放疗(PORT)的场景下,联用激素治疗是否同样能提升总生存期尚不明确。本文报道一项基于随机对照试验的个体患者数据(IPD)meta分析,旨在量化术后放疗联用激素治疗的获益。

方法

本研究为个体患者数据meta分析,纳入了比较术后放疗联合或不联合激素治疗的随机III期临床试验。于2024年12月15日对MEDLINE、Embase、临床试验注册库、Web of Science、Scopus及相关会议论文集进行系统文献检索。个体患者数据通过MARCAP联盟获取。主要结局为总生存期。通过meta分析评估术后放疗基础上联用激素治疗、短期激素治疗(4–6个月)或长期激素治疗(24个月)的获益。基于术前前列腺特异性抗原(PSA)水平与激素治疗时长进行交互作用检验,并构建术前PSA与总生存期之间的非线性关联模型。本研究在MARCAP联盟总方案下开展(PROSPERO注册号:CRD42019134376)。

结果

共纳入6项随机试验、6057例患者,中位随访时间9.0年(IQR7.2–10.7年)。放疗基础上联用激素治疗未显著改善总生存期(风险比HR=0.87,95%CI 0.76–1.01,p=0.06)。激素治疗时长与该效应之间未观察到显著交互作用(p-interaction=0.17),但术前PSA>0.5ng/mL与≤0.5ng/mL组间存在显著交互作用(p-interaction=0.02)。在不区分术前PSA水平时,术后放疗联合或不联合短期激素治疗(n=3938)患者总生存期风险比的95%置信区间上限均跨越1.0。在术后放疗联合或不联合长期激素治疗的患者中(n=1088),当PSA>1.6ng/mL时,总生存期风险比的95%置信区间上限低于1.0。

解释

本研究提供了迄今为止最高级别证据,对于术前PSA≤0.5ng/mL的患者,在术后放疗基础上增加短期或长期激素治疗,均未观察到具有临床意义的总生存期获益,且短期与长期激素治疗的疗效无明显差异。目前仍迫切需要可预测激素治疗潜在获益的生物标志物

Funding

National Institutes of Health.

Declaration of interests

AUK reports grant support from the NIH (P50CA09213 and 1R37CA292795) and the Department of Defense (PC210066); contracts from Novartis, Janssen, Lantheus, Varian Medical Systems, and ViewRay Systems; consulting fees from Lantheus, Varian Medical Systems, Novartis, and Janssen; honoraria from Janssen, Boston Scientific, Varian Medical Systems, and Lantheus, and low-value stock in MiraDx and Alethian AI. CCP reports consulting fees from Novartis and Janssen and participation on a data safety montoring board or advisory board for Telix. MRS reports previous emplyoment with the UKRI-MRI; grant suppport from Astellas, Janssen and Sanofi-Aventis; honoraria from Eisai, Eli-Lily, and Janssen; support for travel from the Health Research Board of Ireland, the Trials Methodology Network in Ireland, and the National Cancer Grid in India; and previous participation in several data monitoring committees in an unpaid capacity. LFV reports grants from Bristol Myers Squibb Foundation Winn CDA, National Institutes of Health SPORE Career Enhancement Program, Mike Slive Foundation for Prostate Cancer Research, The Parker Institute for Cancer Immunotherapy, and the US Department of Veteran Affairs; and consulting fees from the Dedham Group and Health Advances. JES reports grants from the National Institutes of Health and Congressionally Directed Medical Research Programs; consulting fees from Boston Scientific and Engaged MD; honoraria from Onclive; and a leadership or fiduciary role in the American Urological Association. JAG reports consulting fees from AstraZeneca, BeiGene USA, Dava Oncology, GlaxoSmithKline, MJH Life Sciences, Pfizer, and Urogen Pharma. JRB reports honoraria from Ipsen and Merck; support for attending meetings or travel for Johnson & Johnson; and participation in data safety monitoring boards or advisory boards for AstraZeneca, Pfizer, and Johnson & Johnson. MBR reports consulting fees from Immune Bio; honoraria from Bayer and Johsnon&Johnson; and a patent for Inhibitors of the N-terminal domain of the androgen receptor. AES reports consulting fees from Adaptyx Biosciences; honoraria from OncLive, ScientiaCME, Targeted Oncology, Eisai; and participation on a data safety monitoring board or advisory board for Aveo Oncology, Bristol Myers Squibb, Eisai, and Exelixis. SE reports consulting fees with Janssen. SR reports grant support from the Prostate Cancer Foundation; honoraria from Specialty Network; and stock with Merck, Pfizer, Eli Lilly, and Johnson & Johnson. NGZ reports grants from the American Cancer Society—Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG-20-013-01-CCE (2020–) and the Department of Defense (2020–). AYJ reports grants from Novartis and honoraria from Novartis. JAE reports grants from Blue Earth Diagnostics; consulting fees from Blue Earth Diagnostics, Boston Scientific, and Clarity Pharmaceuticals; honoraria from Elekta, IBA, Genentech, UpToDate, Pfizer, and Astellas; participation on a data safety monitoring board or advisory board for Myovant Sciences, Janssen, Johnson & Johnson, Bayer Healthcare, Progenics Pharmaceuticals, Pfizer, Gilead, Lantheus, Angiodynamics, Bioprotect, MDxHealth, and Boston Scientific; and leadership or fiduciary roles as a board member for the Massachusetts Prostate Cancer Coalition, American College of Radiology, and Radiation Oncology Institute; as well as functioning as the Co-Chair of the NCI GU Steering Committee. OM reports honoraria from Bayer. JJD reports funding from National Cancer Institute and US National Institutes of Health. AP reports a leadership role as the co-chair emeritus of the GU translational research programme at NRG oncology. HMS reports leadership roles as a member of the Board of Directors for ASTRO and Speed of Light, The ASTRO Foundation. PLN reports grants from Bayer, Astellas, and Janssen; consulting fees from Boston Scientific, Augmenix, Janssen, Blue Earth, MDxhealth, AIQ, Novartis, and Bayer; a ledership role in NRG Oncology as the GU Chair; and stock or stock options in Nonocan, Reversal Therapeutics, and Strategen Bio. DES reports grant funding from the National Institutes of Health (U01); consulting fees from Boston Scientific; and honoraria from AstraZeneca, Astellas, Bayer, Blue earth, Janssen, Novartis, and Pfizer. All other authors declare no competing interests.



中文翻译仅供参考,所有内容以英文原文为准。

DOI: 10.1016/S0140-6736(26)00137-6


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《柳叶刀》前列腺癌委员会重大报告指出,预计全球前列腺癌的患病人数将从2020年的140万例增加到2040年的290万例,患病人数将翻倍,中低收入国家的增幅最大;全球每年死于前列腺癌的人数将从2020年的37.5万增加到2040年的近70万,增幅约为85%。

人口老龄化和预期寿命的延长使得未来老年男性人数增加。由于前列腺癌的主要危险因素,如年龄在50岁以上以及有家族史,是不可改变的因素,因此无法通过改变生活方式或预防干预措施来避免即将激增的病例数。

作者建议,可使用核磁共振成像(MRI)扫描结合PSA检测对高收入国家的前列腺癌高风险男性人群进行筛查。在中低收入国家,尚未对人群水平PSA检测的有效性进行研究,需要尽快在这些国家开展PSA筛查试验。在中低收入国家推广能够早期诊断前列腺癌的新方法至关重要,因为这些国家的前列腺癌大多为转移性的,即晚期癌症已经扩散到身体的其他部位(通常是骨骼)。与早期前列腺癌的相比,被诊断为晚期前列腺癌的男性存活的时间要短得多。

报告的共同作者指出,中国前列腺癌的发病率正在快速增长,亟需推进早期筛查。

《中国前列腺癌筛查与早诊早治指南(2022,北京)》指出[1],前列腺癌筛查包括:


  • 预期寿命10年以上高风险男性,在充分知晓筛查获益和危害后,可进行前列腺癌筛查
  • 推荐首选PSA作为前列腺癌筛查手段,PSA的临界值为4.0 ng/ml
  • 已接受筛查且预期寿命10年以上的男性,推荐每2年检测1次血清PSA
  • PSA检测水平<1.0 ng/ml的60岁及以上男性停止筛查
  • 年龄≥75岁的男性结合个人健康状况选择是否停止筛查
  • 预期寿命<10年者停止筛查

高风险男性包括:

  • 年龄≥60岁年龄;
  • 年龄≥45岁且有前列腺癌家族史;
  • 携带BRCA2基因突变且年龄≥40岁

References
[1] 赫捷, 陈万青, 等. 中国前列腺癌筛查与早诊早治指南(2022,北京). 中华肿瘤杂志 2022, 44(1):29-53.


题图 Copyright: Linda Raymond/GettyImages        

中文翻译仅供参考,所有内容以英文原文为准。

DOI: 10.1016/S0140-6736(24)00651-2


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重大报告 | 2020至2040年间,预计全球前列腺癌患病人数将翻倍

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