Related Experiment Video

Updated: Jul 28, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

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Genomic Predictors of Response to Metastasis-directed Therapy With or Without Androgen Deprivation Therapy

Philip Sutera1, Kim Van der Eecken2, Yang Song3

  • 1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

European Urology Oncology
|September 21, 2025
PubMed

Insights

Metastasis-directed therapy (MDT) combined with androgen deprivation therapy (ADT) may benefit prostate cancer patients with high-risk mutations. These genetic markers can guide personalized treatment decisions for metachronous oligometastatic castration-sensitive prostate cancer.

Area of Science:

  • Oncology
  • Genetics
  • Urology

Background:

  • Metastasis-directed therapy (MDT) shows promise for metachronous oligometastatic castration-sensitive prostate cancer (omCSPC).
  • Optimal combination strategies for MDT and androgen deprivation therapy (ADT) remain unclear.
  • Personalization of MDT for omCSPC requires further investigation.

Purpose of the Study:

  • To evaluate the efficacy of combined ADT and MDT in omCSPC.
  • To identify genomic alterations that predict response to MDT.
  • To explore the prognostic and predictive value of genetic biomarkers in omCSPC.

Main Methods:

  • Analysis of patients with omCSPC treated with combined ADT and MDT.
  • Genomic profiling to identify high-risk (HiRi) mutations (TP53, BRCA1/2, ATM, Rb1).
  • Correlation of mutation status with treatment response and progression-free survival.

Main Results:

  • HiRi mutations in TP53, BRCA1/2, ATM, and Rb1 are associated with poor prognosis in omCSPC.
  • Patients with HiRi mutations demonstrated a greater benefit from the addition of ADT to MDT.
  • These genetic alterations serve as predictive biomarkers for intensified treatment.

Conclusions:

  • Genomic biomarkers can aid in personalizing MDT for omCSPC.
  • HiRi mutations identify patients who may benefit from combined ADT and MDT.
  • This approach may help optimize treatment strategies for omCSPC.
Keywords:
Castration-sensitive prostate cancerGenomicsMetastasis-directed therapyOligometastasisPersonalized medicine

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