Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

De Novo Metastatic Prostate Cancer: Are We Moving towards a Personalized Treatment?

Version 1 : Received: 7 September 2023 / Approved: 8 September 2023 / Online: 11 September 2023 (07:17:07 CEST)

A peer-reviewed article of this Preprint also exists.

Piombino, C.; Oltrecolli, M.; Tonni, E.; Pirola, M.; Matranga, R.; Baldessari, C.; Pipitone, S.; Dominici, M.; Sabbatini, R.; Vitale, M.G. De Novo Metastatic Prostate Cancer: Are We Moving toward a Personalized Treatment? Cancers 2023, 15, 4945. Piombino, C.; Oltrecolli, M.; Tonni, E.; Pirola, M.; Matranga, R.; Baldessari, C.; Pipitone, S.; Dominici, M.; Sabbatini, R.; Vitale, M.G. De Novo Metastatic Prostate Cancer: Are We Moving toward a Personalized Treatment? Cancers 2023, 15, 4945.

Abstract

De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5-10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since 2015, the prognosis of mHSPC has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. This review describes the current therapeutic opportunities in de novo mHSPC, focusing on potential molecular biomarkers identified in the main clinical trials that have changed the standard of care, the genomic features of de novo mHSPC, and the principal ongoing trials that are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment in this setting. The road towards a personalized treatment for de novo mHSPC is still long considering that the randomized clinical trials, which have furnished the basis of the current therapeutic options, stratified patients according to clinical criteria that not necessarily reflect the biological rationale of the chosen therapy. The role of transcriptomic profiling of mHSPC as predictive biomarker requires further validation, as well as it remains to ascertain how the genomic alterations detected in mHSPC, that are considered predictive in the castration-resistant disease, can be exploited in the mHSPC setting.

Keywords

metastatic hormone-sensitive prostate cancer; new hormonal agents; transcriptomic profiling; DNA damage repair genes; tumor suppressor genes; androgen receptor; immunotherapy; CDK4/6 inhibitors; PARP inhibitors; AKT inhibitors.

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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