ArticleProstate cancer and prostatic diseases2022
Impact of DNA damage repair defects on response to PSMA radioligand therapy in metastatic castration-resistant prostate cancer.
Article in Prostate cancer and prostatic diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Therapeutic sensitivity to standard treatments in BRCA positive metastatic castration-resistant prostate cancer patients-a systematic review and meta-analysis.Prostate cancer and prostatic diseases · 2023Pooled it
- Trial
- Tumor microenvironment-mediated hematologic toxicity ofWorld journal of urology · 2026Review
- Association of Prior PARP Inhibitor Exposure with Clinical Outcomes afterEuropean urology oncology · 2026Article
- Variable cellular and radiobiological effects of [Journal of experimental & clinical cancer research : CR · 2026Article
- α-Therapy and Combination Strategies to Overcome Resistance and Enhance Clinical Outcomes in Prostate Cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Genomic alterations and associated outcomes in patients with PSMA-positive metastatic castration-resistant prostate cancer treated with 177Lu-PSMA-617.The oncologist · 2025Article
- Bridging the Gap: PSMA Radioligand Therapy for Asian Men with Prostate Cancer.Nuclear medicine and molecular imaging · 2025Review
- Design ofAnnals of translational medicine · 2024Review
- [European journal of nuclear medicine and molecular imaging · 2024Article
- Role of Lutetium Radioligand Therapy in Prostate Cancer.Cancers · 2024Review
- Genomic Correlates of Prostate-Specific Membrane Antigen Expression and Response toJCO precision oncology · 2024Article
- Radiotheranostics in advanced prostate cancer: Current and future directions.Prostate cancer and prostatic diseases · 2024Review
- Implementing Ac-225 labelled radiopharmaceuticals: practical considerations and (pre-)clinical perspectives.EJNMMI radiopharmacy and chemistry · 2024Review
- Impact ofTheranostics · 2024Article
- Article
- Status ofWorld journal of urology · 2023Article
- PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study.Cancers · 2022Article
- DNA Damage Repair Defects and Targeted Radionuclide Therapies for Prostate Cancer: Does Mutation Really Matter? A Systematic Review.Life (Basel, Switzerland) · 2022Review
- Genomic biomarkers to guide precision radiotherapy in prostate cancer.The Prostate · 2022Review
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeProstate-specific membrane antigen radioligand therapy (PSMA-RLT) is a novel treatment for castration-resistant prostate cancer (mCRPC). While the majority of patients responds to PSMA-RLT, with 10-15% having an exceptional response, approximately 30% of patients is unresponsive to PSMA-RLT. The molecular underpinning may in part explain these varying responses. This study investigated alterations in DNA damage repair (DDR) genes in tumour biopsies and their association with response to PSMA-RLT.
methodsA predefined retrospective cohort study was performed in mCRPC patients of whom the tumours had undergone next-generation sequencing of 40 DDR genes and received Lu-177-PSMA and/or Ac-225-PSMA-RLT. The primary outcome of this study was to compare the progression free survival (PFS) after PSMA-RLT for patients with and without pathogenic DDR aberrations in their tumour. Secondary outcomes were prostate-specific antigen (PSA) response and overall survival (OS).
resultsA total of 40 patients were included of which seventeen had a tumour with a pathogenic DDR aberration (DDR+), of which eight had defects in BRCA1/2. DDR+ patients had an equal varying response to PSMA-RLT compared to those without pathological DDR anomalies (DDR-) in terms of PFS (5.9 vs. 6.4 months, respectively; HR 1.14; 95% CI 0.58-2.25; p = 0.71), ≥50% PSA response (59% vs. 65%, respectively; p = 0.75) or OS (11.1 vs. 10.7 months, respectively; HR 1.40; 95% CI: 0.68-2.91; p = 0.36).
conclusionIn this study of a selected cohort, pathogenic DDR aberrations were not associated with exceptional responsiveness to PSMA-RLT. Translational studies in larger prospective cohorts are warranted to associate DDR gene defects with differential responses to PSMA-RLT.
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