Molecular reflex testing in patients with early metastatic castration-resistant prostate cancer within the PROMPT-study
A partir de l'analyse moléculaire de 340 échantillons tissulaires issus de 307 patients atteints d'un cancer métastatique de la prostate résistant à la castration, cette étude identifie les variables clinicopathologiques associées à la présence ou l'absence de génotypes tumoraux pouvant être ciblés par des médicaments prédéfinis
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.
British Journal of Cancer , article en libre accès, 2025