Treatment Strategies in Metastatic Castration-Resistant Prostate Cancer: A Narrative Review of Considerations in the...

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.