Treatment Strategies in Metastatic Castration-Resistant Prostate Cancer: A Narrative Review of Considerations in the Post-ARTA, Post-Docetaxel Setting.

IF 3.4 Q2 ONCOLOGY

Oncology and Therapy Pub Date : 2026-03-01 Epub Date: 2026-01-19 DOI:10.1007/s40487-025-00412-9

Kenrick Ng, Birth-Lynn Tyers, Aruni Ghose, Abbas Kassamali, Reem El Debri, Jonathan Shamash

{"title":"Treatment Strategies in Metastatic Castration-Resistant Prostate Cancer: A Narrative Review of Considerations in the Post-ARTA, Post-Docetaxel Setting.","authors":"Kenrick Ng, Birth-Lynn Tyers, Aruni Ghose, Abbas Kassamali, Reem El Debri, Jonathan Shamash","doi":"10.1007/s40487-025-00412-9","DOIUrl":null,"url":null,"abstract":"<p><p>The management of advanced prostate cancer has evolved significantly with the advent of androgen receptor-targeted agents (ARTAs) and docetaxel, which now form the cornerstone of first-line systemic therapy in advanced disease. However, as increasing numbers of patients progress after exposure to both an ARTA and docetaxel, optimal treatment sequencing in the post-ARTA, post-docetaxel metastatic castration-resistant prostate cancer (mCRPC) setting remains an area of clinical uncertainty, with limited comparative data to guide decisions. This narrative review synthesises the current evidence surrounding treatment strategies for mCRPC in this later-line setting. Available therapeutic options include radioligand therapy (e.g. lutetium-177-PSMA-617), cabazitaxel, PARP inhibitors (particularly for patients with DNA repair gene alterations), second-line ARTAs, further chemotherapy and immunotherapeutic approaches. However, direct head-to-head trials comparing these modalities are sparse, and much of the available data comes from retrospective or subgroup analyses, necessitating a nuanced interpretation of outcomes and limitations. Beyond efficacy, this article emphasises the critical role of practical and individualised considerations in therapy selection. These include toxicity profiles, patient comorbidities and preferences, biomarker-driven stratification (e.g. BRCA status, PSMA expression, sites of metastases), and health system factors such as drug availability and reimbursement policies, which may significantly influence access to optimal care. Finally, the review provides an overview of promising emerging therapies poised to expand the treatment landscape for mCRPC. These include bispecific T cell engagers, androgen receptor degraders, and antibody-drug conjugates, which are currently under investigation in clinical trials and may soon offer new avenues for treatment beyond traditional mechanisms.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"173-187"},"PeriodicalIF":3.4000,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992898/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncology and Therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40487-025-00412-9","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The management of advanced prostate cancer has evolved significantly with the advent of androgen receptor-targeted agents (ARTAs) and docetaxel, which now form the cornerstone of first-line systemic therapy in advanced disease. However, as increasing numbers of patients progress after exposure to both an ARTA and docetaxel, optimal treatment sequencing in the post-ARTA, post-docetaxel metastatic castration-resistant prostate cancer (mCRPC) setting remains an area of clinical uncertainty, with limited comparative data to guide decisions. This narrative review synthesises the current evidence surrounding treatment strategies for mCRPC in this later-line setting. Available therapeutic options include radioligand therapy (e.g. lutetium-177-PSMA-617), cabazitaxel, PARP inhibitors (particularly for patients with DNA repair gene alterations), second-line ARTAs, further chemotherapy and immunotherapeutic approaches. However, direct head-to-head trials comparing these modalities are sparse, and much of the available data comes from retrospective or subgroup analyses, necessitating a nuanced interpretation of outcomes and limitations. Beyond efficacy, this article emphasises the critical role of practical and individualised considerations in therapy selection. These include toxicity profiles, patient comorbidities and preferences, biomarker-driven stratification (e.g. BRCA status, PSMA expression, sites of metastases), and health system factors such as drug availability and reimbursement policies, which may significantly influence access to optimal care. Finally, the review provides an overview of promising emerging therapies poised to expand the treatment landscape for mCRPC. These include bispecific T cell engagers, androgen receptor degraders, and antibody-drug conjugates, which are currently under investigation in clinical trials and may soon offer new avenues for treatment beyond traditional mechanisms.

Abstract Image

查看原文本刊更多论文

转移性去势抵抗性前列腺癌的治疗策略：在arta后，后多西他赛设置考虑的叙述性回顾。

随着雄激素受体靶向药物（ARTAs）和多西他赛的出现，晚期前列腺癌的治疗发生了重大变化，这两种药物现已成为晚期疾病一线全身治疗的基石。然而，随着越来越多的患者在同时接受ARTA和多西紫杉醇治疗后病情进展，在ARTA和多西紫杉醇后转移性阉割抵抗性前列腺癌（mCRPC）的最佳治疗序列仍然是一个临床不确定的领域，指导决策的比较数据有限。这篇叙述性综述综合了目前关于晚期mCRPC治疗策略的证据。可用的治疗方案包括放射配体治疗（如黄体-177- psma -617）、卡巴他赛、PARP抑制剂（特别是对DNA修复基因改变的患者）、二线ARTAs、进一步化疗和免疫治疗方法。然而，比较这些模式的直接正面试验很少，而且大部分可用数据来自回顾性或亚组分析，因此需要对结果和局限性进行细致的解释。除了疗效，这篇文章强调了在治疗选择中实用性和个体化考虑的关键作用。这些因素包括毒性概况、患者合并症和偏好、生物标志物驱动的分层（如BRCA状态、PSMA表达、转移部位）以及卫生系统因素，如药物可获得性和报销政策，这些因素可能会显著影响获得最佳护理的机会。最后，本综述概述了有望扩大mCRPC治疗前景的新兴疗法。这些包括双特异性T细胞接合物、雄激素受体降解物和抗体-药物偶联物，它们目前正在临床试验中进行研究，并可能很快为传统机制之外的治疗提供新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Oncology and Therapy ONCOLOGY-

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

6 weeks

期刊介绍： Now indexed in PubMed Aims and Scope Oncology and Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Oncology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid and efficient communication of the latest research and reviews, allowing the advancement of clinical therapies. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts. Digital features and plain language summaries Oncology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Please see here for further information on preprint sharing: https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550 Peer Review Process Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case by case basis and should be sent to the journal editor. Copyright Oncology and Therapy''s content is published open access under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0 Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of £3650/€4500/$5100. The journal will consider fee discounts for developing countries and this is decided on a case by case basis. Open Access All articles published by Oncology and Therapy are published open access Contact For more information about the journal, including pre-submission enquiries, please contact managing editor Lydia Alborn at lydia.alborn@springer.com.