Management of metastatic prostate cancer

Prostate cancer is the most frequently diagnosed type of neoplasm among male patients worldwide and a lea­ding cause of cancer-related death. Despite advances in early de­tec­tion, the rising proportion of distant-stage diag­no­ses – particularly among younger patients – sig­nals an urgent need for timely screening. Androgen de­pri­va­tion therapy, achieved through GnRH agonists or an­ta­go­nists to suppress serum testosterone below 50 ng/dL, con­ti­nues to be the cornerstone of systemic treatment, aiming to extend survival and preserve the quality of life. The current management of metastatic prostate cancer is anchored in consensus recommendations from both European and American guidelines, which integrate in­sights from pivotal clinical trials. Landmark studies such as LATITUDE, TITAN, ARCHES and ARANOTE have defined up­front intensification strategies in hormone-sensitive di­sease, with PEACE-1 and ARASENS further refining pa­tient selection and combination regimens, such as triple therapy. In the castration-resistant setting, PROPEL and PROFOUND have reshaped systemic sequencing and bio­marker-driven approaches. These guidelines and trial out­comes collectively structure the key takeaways for op­ti­mi­zing survival and quality of life across both treat­ment phases. This systematic review synthesizes current evi­dence on systemic therapies in metastatic hormone-sen­si­tive (mHSPC) and castration-resistant prostate cancer (mCRPC), evaluating the roles of upfront chemotherapy and androgen receptor pathway inhibitors in mHSPC along­side the integration of ARPIs and PARP inhibitors, che­mo­therapy and radiopharmaceuticals in mCRPC. By critically appraising clinical trial data and guideline re­com­men­da­tions, we aim to clarify optimal sequencing and combination strategies across both disease phases. To optimize outcomes, enhanced patient profiling – in­cor­po­ra­ting genomic, molecular and clinical predictive and prog­nos­tic factors – is essential for guiding the sequential use of available therapies and for personalizing treatment decisions.