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Personalized therapy in metastatic hormone-sensitive prostate cancer: a 2026 update on navigating therapeutic

Magdalena Koett1, Nastasiia Artamonova, Isabel Heidegger

  • 1Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.

Current Opinion in Urology
|July 4, 2026
PubMed
Abstract

Insights

Biomarker-driven strategies, including PARP inhibitors for HRR-altered disease, are improving outcomes in metastatic hormone-sensitive prostate cancer (mHSPC). Further data are needed to define optimal sequencing and patient selection for these advanced treatments.

Area of Science:

  • Oncology
  • Genitourinary Cancers
  • Prostate Cancer Research

Background:

  • Metastatic hormone-sensitive prostate cancer (mHSPC) management is evolving from clinical characteristics to complex doublet and triplet therapies.
  • Tumor biology insights are driving a shift towards biomarker-driven decision-making algorithms in mHSPC treatment.

Purpose of the Study:

  • To review recent advancements in mHSPC treatment strategies.
  • To incorporate new data from ESMO 2025 and ASCO GU 2026 into the current mHSPC treatment landscape.

Main Methods:

  • Review of Phase III trials presented at ESMO 2025 focusing on biomarker-driven strategies.
  • Analysis of Phase II studies presented at ASCO GU 2026 exploring emerging concepts.
  • Evaluation of data on poly(ADP-ribose) polymerase (PARP) inhibitors, AKT inhibitors, and prostate-specific membrane antigen (PSMA)-targeted radioligand therapy.

Main Results:

  • Phase III trials support earlier integration of biomarker-driven strategies like PARP inhibition (HRR-altered), AKT inhibition (PTEN-deficient), and PSMA-targeted radioligand therapy.
  • These approaches show consistent improvement in radiographic progression-free survival (rPFS), but overall survival (OS) data are immature and quality-of-life benefits vary.
  • Phase II studies highlight intensified androgen receptor blockade and biomarker-guided de-escalation as emerging concepts.

Conclusions:

  • Recent data confirm a trend towards biomarker-driven management in mHSPC.
  • Further maturation of clinical outcomes and balancing efficacy with toxicity are crucial for widespread clinical adoption.
Keywords:
AKT inhibitorsbiomarker-guided therapieshormonal therapymetastatic hormone-sensitive prostate cancerpersonalized treatmentpoly(ADP-ribose) polymerase inhibitorsprostate cancerradioligand therapy

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