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Challenges of diagnosing homologous recombination deficiencies in metastatic prostate cancer: a six-year experience from a single institution

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Abstract

Purpose

We evaluated the prevalence of homologous recombination deficiencies (HRD) to determine the efficacy of different techniques and clinical characteristics of patients.

Methods

This retrospective study included patients with metastatic prostate cancer who underwent molecular testing at our hospital between 2016 and 2022. We used tumor tissue, ctDNA, and lymphocytes for somatic or germline testing. We analyzed the clinical characteristics and survival outcomes.

Results

144 patients were tested (113 somatic, 21 germline, and 10 both). Technical issues prevented the analysis of 23 prostatic samples (18.7%). 12 (8.3%) patients had HRD. BRCA2 was the most frequent mutation (66.7%). Patients with HRD were younger (57.5 years). Patients with BRCA mutations had poorer survival (31.9 vs 56.3 months, p = 0.048).

Conclusion

In our institution, 8.3% of the patients had HRD. Tumor tissue analysis failed in 18.7% of tests. ctDNA analysis is an alternative detection method. BRCA mutations are correlated with poor prognosis.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Flippot R, Patrikidou A, Aldea M, Colomba E, Lavaud P, Albigès L, et al. PARP inhibition, a new therapeutic avenue in patients with prostate cancer. Drugs. 2022;82(7):719–33. https://doi.org/10.1007/s40265-022-01703-5.

    Article  CAS  PubMed  Google Scholar 

  2. de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020;382(22):2091–102. https://doi.org/10.1056/NEJMoa1911440.

    Article  PubMed  Google Scholar 

  3. Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, TRITON3 Investigators, et al. Rucaparib or physician’s choice in metastatic prostate cancer. N Engl J Med. 2023;388(8):719–32. https://doi.org/10.1056/NEJMoa2214676.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pascual J, Attard G, Bidard FC, Curigliano G, De Mattos-Arruda L, Diehn M, et al. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2022;33(8):750–68. https://doi.org/10.1016/j.annonc.2022.05.520.

    Article  CAS  PubMed  Google Scholar 

  5. Castro E, Romero-Laorden N, Del Pozo A, Lozano R, Medina A, Puente J, et al. PROREPAIR-B: a prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(6):490–503. https://doi.org/10.1200/JCO.18.00358.

    Article  CAS  PubMed  Google Scholar 

  6. Matsubara N, de Bono J, Olmos D, Procopio G, Kawakami S, Ürün Y, et al. Olaparib efficacy in patients with metastatic castration-resistant prostate cancer and BRCA1, BRCA2 or ATM alterations identified by testing circulating tumor DNA. Clin Cancer Res. 2023;29(1):92–9. https://doi.org/10.1158/1078-0432.CCR-21-3577.

    Article  CAS  PubMed  Google Scholar 

  7. Trujillo B, Wu A, Wetterskog D, Attard G. Blood-based liquid biopsies for prostate cancer: clinical opportunities and challenges. Br J Cancer. 2022;127(8):1394–402. https://doi.org/10.1038/s41416-022-01881-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hussain M, Corcoran C, Sibilla C, Fizazi K, Saad F, Shore N, et al. Tumor genomic testing for >4000 men with metastatic castration-resistant prostate cancer in the phase III Trial PROfound (Olaparib). Clin Cancer Res. 2022;28(8):1518–30. https://doi.org/10.1158/1078-0432.CCR-21-3940. (PMID: 35091440).

    Article  CAS  PubMed  Google Scholar 

  9. Chi KN, Barnicle A, Sibilla C, Lai Z, Corcoran C, Barrett JC, et al. Detection of BRCA1, BRCA2, and ATM alterations in matched tumor tissue and circulating tumor DNA in patients with prostate cancer screened in PROfound. Clin Cancer Res. 2023;29(1):81–91. https://doi.org/10.1158/1078-0432.CCR-22-0931.

    Article  CAS  PubMed  Google Scholar 

  10. Schweizer MT, Sivakumar S, Tukachinsky H, Colerman I, De Sarkar N, Yu EY, et al. Concordance of DNA repair gene mutations in paired primary prostate cancer samples and metastatic tissue or cell-free DNA. JAMA Oncol. 2021. https://doi.org/10.1001/jamaoncol.2021.2350.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Olmos D, Lorente D, Alameda D, Cattrini C, Romero-Laorden N, Lozano R, et al. Presence of somatic/germline homologous recombination repair (HRR) mutations and outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) receiving first-line (1L) treatment stratified by BRCA status. Abstract of ASCO Congress 2023. J Clin Oncol. 2023;41(suppl 16):5003.

    Article  Google Scholar 

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Acknowledgements

The authors would like to thank M Llobet and O Ramirez for their contribution to data collection.

Funding

The authors did not receive any funding from the study.

Author information

Authors and Affiliations

  1. Medical Oncology Department, Hospital de La Santa Creu I Sant Pau, Sant Quintí 89, 08025, Barcelona, Spain

    Javier Gavira, Jose Carlos Tapia, Alejandra Romano, Georgia Anguera, María Aguado, Aida Piedra, Freya Bosma, Sofía Sánchez, Cristina Martin, Teresa Ramón y Cajal & Pablo Maroto

  2. Institut d’Investigació Biomèdica Sant Pau (IIB, SANT PAU), Sant Quintí 77-79, 08041, Barcelona, Spain

    Georgia Anguera, Cristina Martin, Teresa Ramón y Cajal & Pablo Maroto

  3. Pathology Department, Fundació Puigvert, Cartagena 340, 08025, Barcelona, Spain

    Ferran Algaba & Yolanda Arce

  4. Department of Cancer Medicine, Gustave Roussy, Villejuif, France

    Javier Gavira

  5. Medical Oncology Department, Velindre Cance Center, Cardiff, United Kingdom

    Jose Carlos Tapia

  6. Department of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

    Aida Piedra

Authors
  1. Javier Gavira
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  2. Jose Carlos Tapia
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  3. Alejandra Romano
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  4. Georgia Anguera
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  8. Sofía Sánchez
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  9. Cristina Martin
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  12. Teresa Ramón y Cajal
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  13. Pablo Maroto
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Contributions

Javier Gavira: Conceptualization, methodology, software, data curation, writing-original draft, writing-review and edition, project administration. Jose Carlos Tapia: Investigation, data curation, writing-original draft and writing—review and edition. Alejandra Romano: Investigation, data curation, writing-review and edition. Georgia Anguera: Investigation, data curation, and writing-review and edition. María Aguado: Investigation, data curation, writing—review and edition. Aida Piedra: Investigation, data curation, writing—review and edition. Freya Bosma: Investigation, data curation, writing—review and edition. Sofía Sánchez: Investigation, data curation, writing—review and edition. Cristina Martin: Investigation, and writing—review and edition. Ferrán Algaba: Methodology, Investigation, and writing—review and edition. Yolanda Arce: Methodology, Investigation, and writing—review and edition. Teresa Ramón y Cajal: Conceptualization, methodology, investigation, data curation, and writing—original draft and reviews. Pablo Maroto: Conceptualization, methodology, data curation, writing-original draft, writing—review and edition, and project administration.

Corresponding author

Correspondence to Javier Gavira.

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Conflict of interest

JG: Speakers’ bureau: Astellas, LEO Pharma. Travel, Accommodation, Expenses: Ipsen, BMS, Novartis, Roche and MSD. JCT: Travel, Accommodations, Expenses: Merck, Pfizer, Roche, MSD and Lily/Genentech. GA participated as Collaborator Investigator in clinical trials using PARPi. Speakers’ Bureau: Astellas Pharma, Ipsen, Bristol Myers Squibb, Merck/Pfizer, Leo pharma. Travel, Accommodations, Expenses: Merck, Ipsen, Bristol Myers Squibb. CM participated as Collaborator Investigator in clinical trials using PARPi. PM: participated as Principal Investigator in clinical trials related to the use of PARPi. Consulting or Advisory Role: Astellas Pharma, Ipsen, BMS, Merck/Pfizer, Bayer, Janssen. Travel, Accommodation, Expenses: Merck/Pfizer, Bayer. The rest of the authors declare no competing financial interest in relation to the work.

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Gavira, J., Tapia, J.C., Romano, A. et al. Challenges of diagnosing homologous recombination deficiencies in metastatic prostate cancer: a six-year experience from a single institution. Clin Transl Oncol (2024). https://doi.org/10.1007/s12094-024-03483-8

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