Genomic Prostate Score for Identifying Biologically Low-risk Disease in Patients with Prostate Cancer Undergoing Active Surveillance, Surgery, or Radiotherapy.

Validated genomic classifiers are recommended for use when this may change the management of patients with prostate cancer (PCa). However, their potential for management de-escalation is unclear. Here, we retrospectively evaluated the 17-gene Genomic Prostate Score (GPS) in patients with clinically localised and locally advanced PCa (n = 409; median follow-up ≥6 yr) managed with active surveillance (AS), radical prostatectomy (RP), or radiotherapy (RT). To evaluate de-escalation potential against metastasis and European Association of Urology (EAU) high-risk biochemical recurrence (BCR), patients with low GPS scores (58% of the study population) were stratified into "concordant" and "discordant" low-risk groups based on agreement with standard National Comprehensive Cancer Network (NCCN) risk categories. The "discordant low-risk" phenotype (NCCN ≥2 but low GPS) proved highly prevalent, comprising 46% of NCCN≥2 AS, 57% of NCCN≥3 RP, 36% of NCCN≥4 RT, and 48% of NCCN5 locally advanced patients. Six-yr event-free survival estimates in these patients were 88% in AS, 100% in RP and RT, and 95% in the locally advanced groups, similar to the 100% 6-yr treatment-free survival seen in all "concordant low-risk" (low GPS and lower-risk NCCN) patients. Overall, identifying a prevalent group with favourable 6-yr outcomes despite high clinical risk supports the feasibility of future trials using genomic classifiers for targeted management de-escalation.