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Clinical Impact of Germline Pathogenic Variants in High-risk Prostate Cancer Treated with Radiotherapy
Javier Galego-Carro1,2,3, Marta Santamariña1,2,4, Ana Blanco-Pérez1,2
1Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
European Urology Open Science
|August 7, 2026
Summary
Pathogenic germline variants in cancer susceptibility genes are common in high-risk prostate cancer patients. These variants impact overall survival and disease progression, highlighting the importance of genetic testing for treatment decisions.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- Pathogenic and likely pathogenic (P/LP) germline variants in cancer susceptibility genes (CSGs) are found in 5-10% of prostate cancer patients.
- The clinical significance of these variants in high-risk prostate cancer is not well understood.
Purpose of the Study:
- To determine the prevalence of P/LP variants in CSGs among patients with high-risk prostate cancer.
- To investigate the association between these variants and oncologic outcomes in patients treated with radiotherapy.
Main Methods:
- A retrospective study of 600 men with high-risk prostate cancer.
- Germline DNA analysis using a 19-gene panel.
- Comparison of variant prevalence with non-cancer controls using Fisher's exact test.
- Time-to-event analyses for overall survival, biochemical recurrence, distant metastasis, prostate cancer-specific mortality, and second primary malignancies in 390 radiotherapy-treated patients.
Main Results:
- P/LP variants were identified in 8.0% of patients.
- CHEK2, ATM, and BRCA2 variants were significantly enriched in patients.
- BRCA1/BRCA2 carriers showed significantly worse overall survival, higher rates of biochemical recurrence, distant metastasis, and prostate cancer-specific mortality.
- CHEK2 carriers had a higher incidence of second primary malignancies.
- ATM carriers did not experience metastatic progression or prostate cancer-specific mortality during follow-up.
Conclusions:
- Germline P/LP variants are prevalent in high-risk prostate cancer.
- These variants define patient subgroups with distinct oncologic outcomes.
- Germline genetic testing can aid in risk stratification and treatment decision-making for high-risk prostate cancer.
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