An evolving arsenal: new hope in fighting advanced prostate cancer

Elijah Vanderkamp^1,#, Jacob M. Parker^1,#, Mark R. Wakefield^2,3, Yujiang Fang^1,2,3,*
1 Department of Microbiology, Immunology & Pathology, Des Moines University, West Des Moines, IA, USA
2 Department of Surgery, University of Missouri School of Medicine, Columbia, MO, USA
3 Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, MO, USA
* Corresponding Author: Yujiang Fang. Email: email
# These authors contributed equally to this work
(This article belongs to the Special Issue: Prostate Cancer: Biomarkers, Diagnosis and Treatment)

Canadian Journal of Urology https://doi.org/10.32604/cju.2026.078273

Received 28 December 2025; Accepted 20 May 2026; Published online 15 July 2026

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Abstract

Prostate cancer (PC) remains a global health challenge with metastatic progression driving PC-related mortality. Understanding the transition from localized disease to advanced disease allows novel therapeutics to be developed against metastatic disease. This is a comprehensive review that synthesizes the pathogenesis of advanced prostate cancer, evaluates key clinical trials in establishing current standards of care, and discusses promising novel therapeutics. This review examines phase III clinical data and phase I/II clinical trials for novel therapeutics. Research was obtained from PubMed, ASCO, and ESMO. All other evidence presented is from peer-reviewed journals obtained from PubMed. PC treatment has transitioned from androgen deprivation therapy (ADT) monotherapy to more sophisticated doublet and triplet regimens. Trials such as CHAARTED, STAMPEDE, and LATITUDE have established the use of docetaxel and AR signaling inhibitors (ARSIs) in hormone-sensitive disease. Whereas in metastatic castration-resistant PC (mCRPC), the TROPIC trials established cabazitaxel as a second-line therapy, and the VISION and PSMAfore trials validated 177-Lu-PSMA-617 radioligand therapy. This review also highlights the PROfound and TRITON3 trials that validated PARP inhibitors for patients with homologous recombination repair (HRR) mutations. Novel therapeutics, including mRNA vaccines, CAR-T, BiTE, and antibody drug conjugates (ADCs), are covered in more detail. To combat resistance, including AR-V7 and neuroendocrine trans-differentiation, early-phase data on AR-degrading PROTACs and Bipolar Androgen Therapy (BAT) are covered. Additionally, the roles of single-cell RNA sequencing (scRNA-seq) and circulating tumor DNA (ctDNA) as prognostic biomarkers are assessed. Managing metastatic PC is transitioning toward a precision-driven model that is incorporating molecular targeted therapy with established systemic therapies. This paper evaluates the current standards of care for patients with mCRPC, including the rise of radioligands such as PSMA-targeted radioligands and PARP inhibitors. This paper evaluates new and upcoming targeted therapies, including CAR-T, BiTEs, and mRNA vaccine therapies.