Prognostic Implications of Very High Decipher Scores in Prostate Cancer: Towards a Refined Genomic Risk Classification.

Background and objective: The 22-gene Decipher genomic classifier (DGC) is validated for risk stratification in prostate cancer. Our aim was to evaluate the association of a novel very high-risk (VHR) group (DGC score >0.85) with recurrence outcomes after radical prostatectomy (RP) and to assess the impact of integrating DGC scores with Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scores and European Association of Urology (EAU) biochemical recurrence (BCR) risk groups on prognostication.

Methods: We retrospectively analyzed data for 1673 patients who underwent RP (2015 and 2022). DGC scores were categorized as low risk (<0.45), intermediate (0.45-0.60), high (0.61-0.85), or VHR (>0.85). BCR was analyzed using the Kaplan-Meier method and log-rank tests. DGC scores were combined with CAPRA-S scores, and separately with EAU BCR risk groups to assess associations with BCR. Associations between DGC scores and adverse pathological features were also evaluated.

Key findings and limitations: Among the 1673 men who underwent RP, the incidence of adverse pathological features (International Society of Urological Pathology grade group ≥4, pT3b/T4, or pN1) increased with increasing DGC score (p < 0.001). DGC VHR was an independent predictor of BCR (hazard ratio 1.70, 95% confidence interval 1.26-2.52; p = 0.008). DGC scores further refined risk stratification within the EAU BCR and CAPRA-S risk groups. Decision curve analysis showed that combining DGC scores with CAPRA-S scores or EAU risk groups yielded a greater net benefit in comparison to using each model alone across the risk threshold range from 0.18 to 0.50. The retrospective, single-institution nature of the study highlights the need for external validation.

Conclusion and clinical implications: A DGC score >0.85 delineates a distinct subgroup with markedly adverse oncologic outcomes. Recognition of this VHR category refines postoperative assessment and supports personalized adjuvant or salvage therapy.