Combination Therapies in Locally Advanced and Metastatic Hormone-sensitive Prostate Cancer.

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Tác giả: Neeraj Agarwal, Gerhardt Attard, Arun A Azad, Ian D Davis, Tanya Dorff, Karim Fizazi, Silke Gillessen, Louise Kostos, Chris Parker, Matthew R Smith, Christopher J Sweeney, Bertrand Tombal

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Switzerland : European urology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 721940

BACKGROUND AND OBJECTIVE: The treatment landscape for advanced prostate cancer has evolved significantly over the past decade. The introduction of docetaxel, androgen receptor pathway inhibitors (ARPIs), poly(ADP-ribose) polymerase inhibitors, and targeted radionuclides has redefined the treatment paradigm, with a focus now on early treatment intensification through combination therapies. This narrative collaborative review summarises the current evidence of combination therapies in locally advanced and metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: We conducted a literature search up to November 2024. Search terms included "metastatic hormone-sensitive prostate cancer", "metastatic castration-sensitive prostate cancer", "locally advanced prostate cancer", "combination", "intensification", and "de-escalation". Articles were selected by the authors based on their scientific merit, clinical impact, and relevance to provide a summary of the evidence surrounding combination therapy in locally advanced prostate cancer and mHSPC. KEY FINDINGS AND LIMITATIONS: A doublet approach with an androgen deprivation therapy (ADT) backbone and an ARPI is now considered the standard treatment for mHSPC, with a triplet regimen incorporating docetaxel considered in select subgroups. Similar efforts to improve survival in the high-risk localised and locally advanced disease setting have led to several trials evaluating the benefit of combination therapy in addition to standard-of-care surgery or radiotherapy with ADT. Continued improvements in survival have turned the focus to optimising patient selection for treatment intensification and, in some cases, de-escalation, with the goal of reducing unnecessary overtreatment and minimising harm from long-term treatment toxicity. This is particularly important with the integration of prostate-specific membrane antigen positron emission tomography, which has led to the earlier detection of metastatic disease. CONCLUSIONS AND CLINICAL IMPLICATIONS: In select subgroups, early treatment intensification with combination therapy leads to improved survival, though it can be associated with long-term toxicity.
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