Metastatic hormone-naïve prostate cancer: a distinct biological entity

Abstract

Metastatic hormone-naïve prostate cancer (mHNPC) is often the initial form of presentation for metastatic prostate cancer and encompasses a heterogeneous patient population with high inter-patient heterogeneity in prognosis and response to therapy. A more precise treatment of mHNPC, guided by evidence-based biomarkers, remains an unmet medical need. In addition, the limited number of representative laboratory models of mHNPC hampers the translation of basic research into clinical applications. We provide a comprehensive overview of the clinical and biological features that characterize mHNPC, highlight molecular data that could explain the unique prognostic characteristics of mHNPC, and identify key open questions.

Keywords: clinical trials; experimental models; metastasis; metastatic hormone-naïve prostate cancer; molecular data; prostate cancer.

Figure 1

Principal pathways targeted in metastatic hormone-naïve prostate cancer (mHNPC). AR and microtubule targeting are already part of the standard of care, and AKT, DNA repair, PSMA, and CDK4/6 targeting are currently under investigation. Abbreviations: AR, androgen receptor; CDK, cyclin-dependent kinase; PSMA, prostate-specific membrane antigen. Figure created with BioRender.

Figure 2

Natural history, molecular alterations, and therapeutic interventions in localized prostate cancer (PCa) and metastatic hormone-naïve prostate cancer (mHNPC). The green line represents the evolution of de novo mHNPC, and the purple line represents the progression of localized PCa. Abbreviations: ADT, androgen deprivation therapy; AR, androgen receptor; CRPC, castration-resistant prostate cancer; Del, deletion; LBD, ligand-binding domain; PARPi, PARP inhibitor; PSMA, prostate-specific membrane antigen; RT, radiotherapy.