How Biomarkers Now Drive First-Line Therapy in mHSPC

The panelists explain why biomarker testing now selects first-line therapy in metastatic hormone-sensitive prostate cancer (mHSPC) rather than only guiding treatment after progression. They review the recent wave of biomarker-defined options at the onset of metastatic disease, including niraparib plus abiraterone for BRCA2-altered disease, talazoparib plus enzalutamide for homologous recombination repair (HRR)-altered disease, capivasertib plus abiraterone for PTEN-deficient disease, and lutetium Lu 177 vipivotide tetraxetan for PSMA-positive disease, warning that delayed or missing results may cost patients a biomarker-matched third agent. The discussion defines an actionable finding as one linked to an approved therapy or randomized evidence of benefit, led by BRCA1/2 alterations, with other HRR genes actionable as a class for certain regimens and mismatch repair deficiency supporting pembrolizumab. SPOP, TP53, and RB1 alterations carry prognostic weight but no matched drug. The panelists favor ordering PTEN immunohistochemistry (IHC) alongside next-generation sequencing on the same tissue block before considering capivasertib.