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

Azad, AA; Kostos, L; Agarwal, N; Attard, G; Davis, ID; Dorff, T; Gillessen, S; Parker, C; Smith, MR; Sweeney, CJ; Tombal, B; Fizazi, K

Author(s): Azad, AA; Kostos, L; Agarwal, N; Attard, G; Davis, ID; Dorff, T; Gillessen, S; Parker, C; Smith, MR; Sweeney, CJ; Tombal, B; Fizazi, K;
Details: Publication Year 2025-04,Volume 87,Issue #4,Page 455-467
Journal Title: European Urology
Publication Type: Review
Abstract: 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.
Keywords: Humans; Male; *Prostatic Neoplasms/drug therapy/pathology; Neoplasm Metastasis; Androgen Antagonists/therapeutic use; Combined Modality Therapy; Neoplasm Staging; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Combination therapy; Doublet therapy; Locally advanced prostate cancer; Metastatic hormone-sensitive prostate cancer; Prostate cancer; Radiotherapy; Triplet therapy
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1016/j.eururo.2025.01.010
Open Access at Publisher's Site: https://doi.org/10.1016/j.eururo.2025.01.010
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-03-14 07:06:18

Last Modified: 2025-03-27 06:22:25