Current opinion in urology · 2026
Personalized therapy in metastatic hormone-sensitive prostate cancer: a 2026 update on navigating therapeutic complexity.
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Koett Magdalena, Artamonova Nastasiia, Heidegger Isabel
Аннотация
PURPOSE OF REVIEW: 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.
RECENT FINDINGS: 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.
SUMMARY: 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.
RECENT FINDINGS: 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.
SUMMARY: 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.