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Hormone naïve metastatic prostate cancer: How to treat it?

OBJECTIVES: Recent landmark studies (GETUG-AFU 15, CHAARTED, STAMPEDE (docetaxel), LATITUDE and STAMPEDE (abiraterone)) have changed the treatment of hormone sensitive metastatic prostate cancer (mHSPC) from androgen deprivation therapy (ADT) only to combined therapy with either docetaxelor abiraterone acetate plus prednisone (AAP) together with ADT. In this Review we highlight current evidence and recommendations on how to treat men with newly diagnosed mHSPC beyond ADT. METHODS: Narrative overview of available evidence retrieved from pubmed searches, hand searches and authoritative texts.

RESULTS: Docetaxel or AAP in combination with ADT improves overall survival (OS) in men fit for combined treatment presenting with newly diagnosed mHSPC. The strongest evidence is for men with high volume mHSPC (four or more bone metastases with at least one outside the axial skeleton and/or visceral metastases) or mHSPC with high risk features (A minimum of two out of three following high-risk features: Gleason score ≥ 8, ≥ 3 bone lesions or visceral metastasis) as per CHAARTED and LATITUDE criteria, respectively. While upfront docetaxel and AAP yield comparable OS improvement, docetaxel has not been shown to increase OS specifically for men with low volume/low risk mHSPC, whereas, a recent post-hoc analysis from the STAMPEDE (abiraterone) trial showed consistent overall survival benefit of AAP plus ADT independent of risk stratification. While these data are limited by their retrospective nature, they do suggest that patients with low-risk mHSPC should be offered AAP. In men with high volume/high risk mHSPC, choosing between six-cycles of docetaxel or AAP until disease progression relies on patient preference, cost and individual assessment of which drug side-effect profile is most suitable.

CONCLUSION: Offer men presenting with newly diagnosed mHSPC fit enough for combined therapy either ADT plus docetaxel or AAP.

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