Packing the Punch: Current and Emerging Treatment Strategies in Metastatic Castration-Sensitive Prostate Cancer

TL;DR

This paper reviews treatment strategies for metastatic castration-sensitive prostate cancer, focusing on how combining therapies improves patient outcomes.

Contribution

The paper highlights the shift from monotherapy to multimodal treatment and evaluates emerging triplet regimens and targeted therapies.

Findings

Triplet therapy (ADT, docetaxel, and ARSI) improves outcomes in high-volume metastatic castration-sensitive prostate cancer.

Combining ADT with docetaxel or ARSIs improves survival compared to monotherapy.

Targeted radionuclides and metastasis-directed radiotherapy may refine personalized treatment approaches.

Abstract

Prostate cancer remains a significant source of morbidity and mortality worldwide, with metastatic castration-sensitive disease (mCSPC) representing a complex therapeutic challenge. This review explores how a deeper understanding of the androgen receptor axis has shifted mCSPC management from monotherapy to more intense treatment. We discuss emerging data on triplet regimens, targeted therapies, and the role of local treatment.

Randomized trials have shown that adding docetaxel or androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) improves survival. Triplet therapy (ADT, docetaxel, and an ARSI) improves outcomes in patients with high-volume disease compared to ADT and docetaxel alone, although comparisons to ADT plus ARSI doublet therapy are ongoing. The early use of targeted radionuclides, biomarker-driven therapies, and metastasis-directed radiotherapy has also emerged, potentially refining treatment personalization in clinical practice.

Current guidelines recommend ADT combined with an ARSI, with the addition of docetaxel reserved for high-volume disease. Future research aims to optimize intensity, inform biomarker-driven strategies, and reduce toxicity. Advancements in management of mCSPC underscore the importance of a multimodal, personalized approach to improve outcomes.

The online version contains supplementary material available at 10.1007/s11934-025-01272-6.