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Background <p>Precision oncology using genotype-matched treatments (GMT) offers potential to improve survival in metastatic castration-resistant prostate cancer (mCRPC).</p> Patient and methods <p>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.</p> Results <p>Analysis included 340 tissue samples from 307 patients, 51% of samples were newly biopsied. Valid results were generated in 84% (76% new, 92% archived; <i>P</i> &lt; 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 (<i>P</i> &lt; 0.01), yielded higher GMT recommendations than primary tissue (<i>P</i> = 0.03). HR-associated genes were linked with shorter ADT-to-CRPC time (OR 3.77, 95%CI 1.62–10.32, <i>P</i> &lt; 0.01). PI3K-AKT alterations were associated with metachronous metastatic disease (OR 0.48, 95%CI 0.26–0.89, <i>P</i> = 0.021) and longer time to CRPC (OR 0.47, 95%CI 0.25–0.87, <i>P</i> = 0.017). No distinct variables predicted DT genotypes.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月31日

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  • Iris S. H. Kloots,
  • Peter H. J. Slootbeek,
  • Sofie H. Tolmeijer,
  • Sandra van Wilpe,
  • Minke Smits,
  • Sjoerd van Helvert,
  • Leonie I. Kroeze,
  • Jolique A. van Ipenburg,
  • Katrien Grünberg,
  • C. Marleen Kets,
  • Marjolijn J. L. Ligtenberg,
  • James Nagarajah,
  • Jurgen Fütterer,
  • Joyce M. van Dodewaard,
  • Theo van Voorthuizen,
  • Frederiek Terheggen,
  • Tineke J. Smilde,
  • Jack A. Schalken,
  • Inge M. van Oort,
  • Haiko J. Bloemendal,
  • Winald R. Gerritsen,
  • Niven Mehra,
  • Joyce M. van Dodewaard,
  • Theo van Voorthuizen,
  • Inge M. van Oort

摘要

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.