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

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.

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.

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.

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.