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. 2025 Oct 31.
doi: 10.1038/s41416-025-03243-7. Online ahead of print.

Molecular reflex testing in patients with early metastatic castration-resistant prostate cancer within the PROMPT-study

Iris S H Kloots  1 , Peter H J Slootbeek  1 , Sofie H Tolmeijer  1 , Sandra van Wilpe  1 , Minke Smits  1 , Sjoerd van Helvert  2 , Leonie I Kroeze  2 , Jolique A van Ipenburg  2 , Katrien Grünberg  2 , C Marleen Kets  3 , Marjolijn J L Ligtenberg  2   3 , James Nagarajah  4 , Jurgen Fütterer  4 , Joyce M van Dodewaard  5 , Theo van Voorthuizen  6 , Frederiek Terheggen  7 , Tineke J Smilde  8 , Jack A Schalken  9 , Inge M van Oort  9   10 , Haiko J Bloemendal  1 , Winald R Gerritsen  1 , Niven Mehra  11 ; PROMPT collaboration network
Collaborators, Affiliations

Molecular reflex testing in patients with early metastatic castration-resistant prostate cancer within the PROMPT-study

Iris S H Kloots et al. Br J Cancer. .

Abstract

Background: Precision oncology using genotype-matched treatments (GMT) offers potential to improve survival in metastatic castration-resistant prostate cancer (mCRPC).

Patient and methods: In the PROMPT study (NCT04746300), reflex tumour testing through next-generation sequencing was performed in treatment-naïve or first-line mCRPC patients. All patients received a molecular tumour board (MTB) recommendation for GMT based on predefined druggable targets (DT). The main objective was to identify clinicopathological variables associated with DT.

Results: Analysis included 340 tissue samples from 307 patients, 51% of samples were newly biopsied. Valid results were generated in 84% (76% new, 92% archived; P < 0.01). DT were identified in 39% of the patients, with PI3K-AKT (26%) and Homologous Recombination (HR; 21%) pathways most frequently affected. Metastatic tissue, especially from mCRPC setting (P < 0.01), yielded higher GMT recommendations than primary tissue (P = 0.03). HR-associated genes were linked with shorter ADT-to-CRPC time (OR 3.77, 95%CI 1.62-10.32, P < 0.01). PI3K-AKT alterations were associated with metachronous metastatic disease (OR 0.48, 95%CI 0.26-0.89, P = 0.021) and longer time to CRPC (OR 0.47, 95%CI 0.25-0.87, P = 0.017). No distinct variables predicted DT genotypes.

Conclusion: Molecular tumour testing should preferably be done on metastatic mCRPC tissue. No combination of features could robustly identify druggable genotypes; therefore, reflex molecular characterisation should be routine for every mCRPC patient.

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Conflict of interest statement

Competing interests: MJL received consulting fees from GlaxoSmithKline B.V., Janssen-Cilag B.V., AstraZeneca; received honoraria for lectures: AstraZeneca, Janssen, Roche, MSD, Pfizer. All payments to Radboudumc. WRG is a member of the advisory boards of Astellas, Coretag holding AG, Merck Sharp and Dohme, and Novartis; received personal fees for coaching activities by Bayer; and is member of the board of directors of ORCA therapeutic B.V. NM received consultancy fees from Astellas Pharma, AstraZeneca, Bayer, Janssen-Cilag, Johnson & Johnson, Merck Sharp and Dohme, and Pfizer; and research funding (all paid to the institution) from Astellas Pharma, AstraZeneca/Merck, Bristol Myers Squibb Foundation, and Janssen-Cilag. All other authors declare that they have no competing interests. Ethics approval and consent to participate: The trial was conducted in accordance with the principles of the Declaration of Helsinki and classified by the medical ethical committee of “Commissie Mensgebonden Onderzoek” (CMO) regio Arnhem-Nijmegen. No ethics approval was needed for this study. All patients provided written informed consent. The study is registered in ClinicalTrials.gov under the number NCT04746300. Consent for publication: Not applicable.

References

    1. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–33. https://doi.org/10.1056/NEJMoa1405095 . - DOI - PubMed - PMC
    1. Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23. https://doi.org/10.1056/NEJMoa1213755 . - DOI - PubMed
    1. 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;382:2091–102. https://doi.org/10.1056/NEJMoa1911440 . - DOI - PubMed
    1. Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385:1091–103. https://doi.org/10.1056/NEJMoa2107322 . - DOI - PubMed - PMC
    1. Westgeest HM, Kuppen MCP, van den Eertwegh AJM, de Wit R, Bergman AM, van Moorselaar RJA, et al. The effects of new life-prolonging drugs for metastatic castration-resistant prostate cancer (mCRPC) patients in a real-world population. Prostate Cancer Prostat Dis. 2021;24:871–9. https://doi.org/10.1038/s41391-021-00344-1 . - DOI

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