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Updated: Jul 19, 2025

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Impact of Somatic DNA Repair Mutations on the Clinical Outcomes of Bone Metastases from Castration-Resistant Prostate

Maria Concetta Cursano1, Emilio Francesco Giunta1, Emanuela Scarpi2

  • 1Department of Medical Oncology, Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"-IRST S.r.l., 47014 Meldola, Italy.

International Journal of Molecular Sciences
|August 12, 2023
PubMed

Insights

DNA damage repair (DDR) gene mutations are common in castration-resistant prostate cancer (CRPC) with bone metastases. While DDR mutations correlate with higher bone metastasis volume, they do not worsen skeletal-related event outcomes.

Area of Science:

  • Oncology
  • Genetics
  • Prostate Cancer Research

Background:

  • Castration-resistant prostate cancer (CRPC) frequently involves bone metastases, affecting up to 80% of patients.
  • Approximately 25% of CRPC patients exhibit mutations in DNA damage repair (DDR) genes, which are crucial for genomic stability.

Purpose of the Study:

  • To investigate the prevalence of DDR gene alterations in CRPC patients with bone metastases.
  • To evaluate the impact of DDR mutations on clinical outcomes related to bone metastases, including skeletal-related events (SREs).

Main Methods:

  • Retrospective observational study analyzing 121 metastatic CRPC (mCRPC) patients with bone metastases.
  • FoundationOne® analysis of tissue or liquid biopsies to determine DDR mutational status at mCRPC diagnosis.
  • Evaluation of bone-related efficacy endpoints, including SRE incidence and time to SRE onset.

Main Results:

  • 38 out of 121 patients (approx. 31%) had mutations in at least one DDR gene.
  • DDR mutated status was significantly associated with increased bone metastases volume (p = 0.006).
  • No significant difference was observed in SRE incidence or time to SRE onset between DDR mutated and non-mutated groups.

Conclusions:

  • DDR gene mutations are prevalent in mCRPC patients with bone metastases.
  • While DDR mutations are linked to higher bone metastatic burden, they do not appear to negatively impact skeletal-related event outcomes.
  • Liquid and tissue biopsies show comparable results for detecting DDR alterations.
Keywords:
DDR deficiencyDNA damage repairSREbone metastasesliquid biopsymCRPCprostate cancersheletal related events

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