AbstractBackgroundThe natural history of biochemical recurrence (BCR) managed with delayed hormonal therapy is well documented by data from Johns Hopkins. However, as many patients receive treatment prior to metastasis, we evaluated the natural history and role of prostate-specific antigen doubling time (PSADT) in a more contemporary cohort of BCR patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC).MethodsPatients in the Veterans Health Administration (VHA; 01/01/06 to 06/22/20) with nmCSPC and BCR were divided into rapid ( ≤9 months) and less rapid ( >9 to ≤15 months) PSADT cohorts.

摘要背景约翰·霍普金斯大学的数据充分证明了延迟激素治疗的生化复发（BCR）的自然史。。方法退伍军人健康管理局（VHA；06年1月1日至20年6月22日）患有nmCSPC和BCR的患者分为快速（≤9个月）和不太快速（>9至≤15个月）的PSADT队列。

Patients with PSADT >15 months were excluded as outcomes, even with delayed treatment, are excellent. Outcomes included time to first antineoplastic therapy after BCR, metastasis, metastasis-free survival (MFS), and overall survival (OS). Cox models adjusted for baseline demographics and clinical characteristics.ResultsOverall, 781 patients with BCR were identified (502 rapid; 279 less rapid PSADT).

PSADT>15个月的患者被排除在外，因为即使延迟治疗，结果也很好。结果包括BCR后首次抗肿瘤治疗的时间，转移，无转移生存期（MFS）和总生存期（OS）。Cox模型根据基线人口统计学和临床特征进行了调整。结果共鉴定出781例BCR患者（502例快速；279例PSADT不太快速）。

Rapid PSADT was associated with shorter time to first systemic antineoplastic therapy (median 11.4 vs. 28.3 months, adjusted hazard ratio [95% confidence interval] 2.17 [1.83–2.57]), metastasis (102.4 months vs. not reached, 1.79 [1.33–2.40]), MFS (76.1 vs. 106.3 months, 1.73 [1.33–2.24]), and OS (120.5 vs.

快速PSADT与首次全身抗肿瘤治疗的时间较短（中位数11.4 vs.28.3个月，调整后的风险比[95%置信区间]2.17[1.83-2.57]），转移（102.4个月vs.未达到，1.79[1.33-2.40]），MFS（76.1 vs.106.3个月，1.73[1.33-2.24]）和OS（120.5 vs。

140.5 months, 1.76 [1.22–2.54]) versus less rapid PSADT.ConclusionMost patients with rapid PSADT underwent secondary treatment within 1 year after BCR. More contemporary patients treated with early secondary treatment had better outcomes than historical data from patients who had delayed treatment. Whether these results reflect the benefits of early secondary treatment or overall improvements in prostate cancer outcomes over time requires further study..

140.5个月，1.76[1.22-2.54]）与不太快的PSADT相比。结论大多数快速PSADT患者在BCR后1年内接受了二次治疗。与延迟治疗的患者的历史数据相比，接受早期二级治疗的当代患者的预后更好。这些结果是否反映了早期二级治疗的益处或随着时间的推移前列腺癌结局的整体改善需要进一步研究。。

IntroductionProstate cancer progresses through a series of characteristic clinical states reflecting the natural history of the disease and response to treatment. Following initial diagnosis and treatment, patients with prostate cancer may experience rising prostate-specific antigen (PSA) levels or biochemical recurrence (BCR).

引言前列腺癌通过一系列反映疾病自然史和治疗反应的特征性临床状态进展。在初步诊断和治疗后，前列腺癌患者可能会出现前列腺特异性抗原（PSA）水平升高或生化复发（BCR）。

Despite BCR, most patients do not develop metastases or die from prostate cancer after primary therapy [1, 2], but are at an increased risk of prostate cancer-related morbidity and mortality [3].Real-world data on treatment patterns and clinical outcomes are limited for patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC) and BCR after primary therapy.

尽管BCR，大多数患者在初次治疗后不会发生转移或死于前列腺癌[1，2]，但前列腺癌相关发病率和死亡率的风险增加[3]。对于初次治疗后的非转移性去势敏感性前列腺癌（nmCSPC）和BCR患者，治疗模式和临床结果的真实数据有限。

Current understanding of the natural history of BCR largely comes from treatment data from the Johns Hopkins Hospital [3, 4]. These studies included patients with BCR following radical prostatectomy (RP) and most patients received delayed androgen deprivation therapy (ADT) at metastasis, with few patients receiving early ADT (prior to metastasis).

目前对BCR自然史的理解主要来自约翰·霍普金斯医院的治疗数据[3，4]。这些研究包括根治性前列腺切除术（RP）后BCR患者，大多数患者在转移时接受延迟雄激素剥夺治疗（ADT），少数患者接受早期ADT（转移前）。

Among all BCR patients, regardless of PSA doubling time (PSADT), median time from BCR to metastasis was 8 years. However, this was dependent on PSADT, with worse outcomes reported for shorter PSADT (especially <3 months) [4]. These data contributed to guidelines recommending observation for patients with low-risk disease with nmCSPC and BCR after primary therapy, with salvage treatment or intermittent ADT recommended for high-risk disease [5,6,7,8].

在所有BCR患者中，无论PSA倍增时间（PSADT）如何，从BCR到转移的中位时间为8年。然而，这取决于PSADT，PSADT较短（尤其是<3个月）的结果较差（4）。这些数据有助于指导原则，建议在初次治疗后观察nmCSPC和BCR的低风险疾病患者，并建议对高危疾病进行补救治疗或间歇性ADT[5,6,7,8]。

However, real-world data show that most patients who receive ADT after BCR do so prior to metastases [9]. The benefits of early ADT are unclear. In TOAD, early ADT improved overall survival (OS) in patients with BCR or non-curable prostate cancer compared with delayed ADT [10]. However, wh.

然而，现实世界的数据显示，大多数在BCR后接受ADT的患者在转移之前就这样做了（9）。早期ADT的益处尚不清楚。在蟾蜍中，与延迟ADT相比，早期ADT改善了BCR或不可治愈前列腺癌患者的总生存期（OS）。然而，wh。

Data availability

数据可用性

As the data supporting the findings of this study were used under license for the current study, restrictions apply to the authors’ ability to make data publicly available. The data are available from the Veterans Health Administration.

由于支持本研究结果的数据是在当前研究的许可下使用的，因此作者公开数据的能力受到限制。。

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Download referencesAcknowledgementsMedical writing and editorial support were provided by Adam Anazim, BSc, Kirstie Anderson, BSc, and Rosie Henderson, MSc, of Onyx (a division of Prime, London, UK) and funded by the sponsors. The authors were involved in the collection and interpretation of information provided in the manuscript, and ultimate responsibility for opinions and conclusions lies with the authors.FundingThis study was sponsored by Pfizer Inc.

下载参考文献致谢医学写作和编辑支持由Onyx（英国伦敦Prime的一个部门）的理学学士Adam Anazim，理学学士Kirstie Anderson和理学硕士Rosie Henderson提供，并由赞助商资助。作者参与了稿件中提供的信息的收集和解释，作者对意见和结论负有最终责任。资助这项研究是由辉瑞公司赞助的。

(New York, NY, USA) and Astellas Pharma Inc. (Northbrook, IL, USA), the co-developers of enzalutamide. Open access funding provided by SCELC, Statewide California Electronic Library Consortium.Author informationAuthors and AffiliationsCedars-Sinai Cancer Center, Los Angeles, CA, USAStephen J. FreedlandThe Durham VA Medical Center, Durham, NC, USAStephen J.

（美国纽约州纽约市）和恩扎鲁胺的联合开发商Astellas Pharma Inc.（美国伊利诺伊州诺斯布鲁克）。由加州全州电子图书馆联盟SCELC提供的开放获取资金。作者信息作者和附属机构美国加利福尼亚州洛杉矶西奈癌症中心Stephen J.Freedland达勒姆VA医学中心，北卡罗来纳州达勒姆，美国Stephen J。

FreedlandAnalysis Group Inc., Boston, MA, USAWei Gao, Angela Lax & Hongbo YangPfizer Inc., New York, NY, USAKrishnan Ramaswamy, David Russell, Agnes Hong & Jasmina I. IvanovaAuthorsStephen J. FreedlandView author publicationsYou can also search for this author in.

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PubMed Google ScholarContributionsConceptualization: SJF, WG, AL, HY, KR, DR, AH, JII; Methodology: WG, AL, HY; Formal analysis and investigation: SJF, WG, AL, HY, KR, DR, AH, JII; Writing – original draft preparation, review, and editing: SJF, WG, AL, HY, KR, DR, AH, JII; Supervision: WG, AL, HY, JII, KR.

PubMed谷歌学术贡献概念：SJF，WG，AL，HY，KR，DR，AH，JII；方法：WG，AL，HY；正式分析和调查：SJF，WG，AL，HY，KR，DR，AH，JII；；监督：WG，AL，HY，JII，KR。

All authors read and approved the final manuscript.Corresponding authorCorrespondence to.

所有作者都阅读并批准了最终手稿。对应作者对应。

Stephen J. Freedland.Ethics declarations

斯蒂芬·J·弗里德兰德。道德宣言

Competing interests

相互竞争的利益

SJF reports consulting for Astellas Pharma Inc., AstraZeneca, Bayer, Eli Lilly, Exact Sciences, Janssen, Merck, Pfizer Inc., Sanofi, and Sumitomo Pharma America Inc. (formerly Myovant Sciences Inc). WG, AL, and HY are employees of Analysis Group. KR, DR, and JII own stocks or stock options in and are employees of Pfizer Inc., a study sponsor.

SJF报告为Astellas Pharma Inc.，AstraZeneca，Bayer，Eli Lilly，Exact Sciences，Janssen，Merck，Pfizer Inc.，Sanofi和Sumitomo Pharma America Inc.（前身为Myovant Sciences Inc.）提供咨询。WG、AL和HY是Analysis Group的员工。KR、DR和JII拥有研究赞助商辉瑞公司的股票或股票期权，并且是辉瑞公司的员工。

AH is an employee of Pfizer Inc., a study sponsor, and owns stock in Veru, Revance, and Insmed..

AH是辉瑞公司（Pfizer Inc.）的员工，辉瑞公司是一家研究赞助商，拥有Veru、Revance和Insmed的股票。。

Ethics approval and consent to participate

道德批准和同意参与

This study was conducted in accordance with legal and regulatory requirements, as well as with scientific purpose, value and rigor and followed generally accepted research practices described in Guidelines for Good Pharmacoepidemiology Practices issued by the International Society for Pharmacoepidemiology..

这项研究是根据法律和法规要求以及科学目的、价值和严谨性进行的，并遵循国际药物流行病学学会发布的《良好药物流行病学实践指南》中描述的公认研究实践。。

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Reprints and permissionsAbout this articleCite this articleFreedland, S.J., Gao, W., Lax, A. et al. Real-world outcomes following biochemical recurrence after definitive therapy with a short prostate-specific antigen doubling time: potential role of early secondary treatment.

转载和许可本文引用本文Freedland，S.J.，Gao，W.，Lax，A。等人。用短的前列腺特异性抗原倍增时间进行确定性治疗后生化复发后的现实世界结果：早期二级治疗的潜在作用。

Prostate Cancer Prostatic Dis (2024). https://doi.org/10.1038/s41391-024-00894-0Download citationReceived: 20 May 2024Revised: 02 September 2024Accepted: 03 September 2024Published: 13 September 2024DOI: https://doi.org/10.1038/s41391-024-00894-0Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

前列腺癌前列腺疾病（2024）。https://doi.org/10.1038/s41391-024-00894-0Download引文收到日期：2024年5月20日修订日期：2024年9月2日接受日期：2024年9月3日发布日期：2024年9月13日OI：https://doi.org/10.1038/s41391-024-00894-0Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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