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Updated: Jan 12, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Molecular reflex testing in patients with early metastatic castration-resistant prostate cancer within the
Iris S H Kloots1, Peter H J Slootbeek1, Sofie H Tolmeijer1
1Department of Medical Oncology, Radboud university medical centre, Nijmegen, The Netherlands.
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.
Insights
Molecular tumor testing in metastatic castration-resistant prostate cancer (mCRPC) is most effective on metastatic tissue. Reflex molecular characterization should be standard for all mCRPC patients to identify druggable targets.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Precision oncology aims to improve survival in metastatic castration-resistant prostate cancer (mCRPC) through genotype-matched treatments (GMT).
- The PROMPT study investigated the utility of next-generation sequencing for identifying druggable targets in mCRPC patients.
Purpose of the Study:
- To identify clinicopathological variables associated with druggable targets (DT) in treatment-naïve or first-line mCRPC patients.
- To evaluate the effectiveness of reflex tumor testing and molecular tumor board recommendations for GMT.
Main Methods:
- Next-generation sequencing was performed on 340 tissue samples from 307 mCRPC patients.
- Molecular tumor board recommendations for GMT were provided based on predefined druggable targets.
- Clinicopathological variables were analyzed to identify associations with identified DT.
Main Results:
- Druggable targets were identified in 39% of patients, with PI3K-AKT (26%) and Homologous Recombination (HR; 21%) pathways being most common.
- Metastatic tissue, particularly from mCRPC, yielded higher GMT recommendations compared to primary tissue.
- HR-associated genes correlated with shorter androgen deprivation therapy (ADT) to CRPC time, while PI3K-AKT alterations were linked to metachronous metastasis and longer time to CRPC.
Conclusions:
- Molecular tumor testing is most informative when performed on metastatic mCRPC tissue.
- No combination of clinical features reliably predicted druggable genotypes.
- Routine reflex molecular characterization is recommended for all mCRPC patients to guide treatment decisions.
