The management of metastatic hormone-sensitive prostate cancer (mHSPC) has rapidly evolved into a complex landscape of doublet and triplet combination strategies. While treatment intensification was initially guided by clinical characteristics, growing insights into tumour biology are reshaping biomarker-driven decision-making algorithms. This review summarizes recent developments in mHSPC and incorporates new data presented at ESMO 2025 and ASCO GU 2026 within the current treatment landscape.
Phase III trials in the mHSPC presented at ESMO 2025 provide clinically relevant evidence supporting the earlier integration of biomarker-driven strategies, including poly(ADP-ribose) polymerase (PARP) inhibition in homologous recombination repair (HRR)-altered disease, protein kinase B (AKT) inhibition in PTEN-deficient tumours, and prostate-specific membrane antigen (PSMA)-targeted radioligand therapy. These approaches consistently improve radiographic progression-free survival (rPFS); however, overall survival (OS) data remain immature, and quality-of-life benefits are variable. The optimal treatment sequencing as well as patient selection remain to be defined. In parallel, phase II studies, presented at ASCO GU 2026, are hypothesis-generating and highlight emerging concepts such as intensified androgen receptor blockade and biomarker-guided treatment de-escalation.
Recent data reinforce the shift toward biomarker-driven management in mHSPC, but further maturation of clinical outcomes and careful balancing of efficacy and toxicity are required before broad clinical implementation.
Current opinion in urology. 2026 Jun 26 [Epub ahead of print]
Magdalena Koett, Nastasiia Artamonova, Isabel Heidegger
Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.