Validation of a 22-Gene Genomic Classifier in Patients With Recurrent Prostate Cancer

Abstract

IMPORTANCE Decipher (Decipher Biosciences Inc) is a genomic classifier (GC) developed to estimate the risk of distant metastasis (DM) after radical prostatectomy (RP) in patients with prostate cancer.OBJECTIVE To validate the GC in the context of a randomized phase 3 trial. DESIGN, SETTING, AND PARTICIPANTSThis ancillary study used RP specimens from the phase 3 placebo-controlled NRG/RTOG 9601 randomized clinical trial conducted from March 1998 to March 2003. The specimens were centrally reviewed, and RNA was extracted from the highest-grade tumor available in 2019 with a median follow-up of 13 years. Clinical-grade whole transcriptomes from samples passing quality control were assigned GC scores (scale, 0-1). A National Clinical Trials Network-approved prespecified statistical plan included the primary objective of validating the independent prognostic ability of GC for DM, with secondary end points of prostate cancer-specific mortality (PCSM) and overall survival (OS). Data were analyzed from September 2019 to December 2019.INTERVENTION Salvage radiotherapy (sRT) with or without 2 years of bicalutamide. MAIN OUTCOMES AND MEASURESThe preplanned primary end point of this study was the independent association of the GC with the development of DM. RESULTSIn this ancillary study of specimens from a phase 3 randomized clinical trial, GC scores were generated from 486 of 760 randomized patients with a median follow-up of 13 years; samples from a total of 352 men (median [interquartile range] age, 64.5 (60-70) years; 314 White [89.2%] participants) passed microarray quality control and comprised the final cohort for analysis. On multivariable analysis, the GC (continuous variable, per 0.1 unit) was independently associated with DM (hazard ratio [HR], 1.17; 95% CI, 1.05-1.32; P = .006), PCSM (HR, 1.39; 95% CI, 1.20-1.63; P < .001), and OS (HR, 1.17; 95% CI, 1.06-1.29; P = .002) after adjusting for age, race/ethnicity, Gleason score, T stage, margin status, entry prostate-specific antigen, and treatment arm. Although the original planned analysis was not powered to detect a treatment effect interaction by GC score, the estimated absolute effect of bicalutamide on 12-year OS was less when comparing patients with lower vs higher GC scores (2.4% vs 8.9%), which was further demonstrated in men receiving early sRT at a prostate-specific antigen level lower than 0.7 ng/mL (−7.8% vs 4.6%). CONCLUSIONS AND RELEVANCEThis ancillary validation study of the Decipher GC in a randomized trial cohort demonstrated association of the GC with DM, PCSM, and OS independent of standard clinicopathologic variables. These results suggest that not all men with biochemically recurrent prostate cancer after surgery benefit equally from the addition of hormone therapy to sRT.

Current State of Personalized Genitourinary Cancer Radiotherapy in the Era of Precision Medicine

“…Decipher has been validated as part of a clinicalgenomic risk group classification for localized prostate cancer to improve risk stratification, finding that 67% of patients would be reclassified from the standard NCCN risk-system by the new system (44). In an ancillary study of the NRG/RTOG 9601 trial, Decipher was validated and independently associated with distant metastases (hazard ratio [HR] 1.17, 95% CI 1.05-1.32, p=0.006), prostate cancer-specific mortality (HR 1.39, 95% CI 1.20-1.63, p<0.001), and overall survival (HR 1.17, 95%CI 1.06-1.29, p=0.002), after adjusting for age, race/ethnicity, Gleason score, T stage, margin status, entry PSA, and treatment arm (45). Based on this data, several trials are incorporating this risk classifier for stratification to either intensification/deintensification treatment based on either high or low genomic risk, respectively (NRG-GU009, NCT0451371).…”

Post-Operative Radiotherapy in Prostate Cancer: Is It Time for a Belt and Braces Approach?

“…In an ancillary study of the RTOG-9601 trial, this score was generated from 352 of 760 randomized patients with a median follow-up of 13 years. On multivariable analysis, the genomic classifier (GC) was independently associated with the risk of distant metastasis (HR 1.17, 95% CI 1.05–1.32; p = 0.006), PCa-specific mortality (HR 1.39, 95% CI 1.20–1.63; p < 0.001), and OS (HR 1.17, 95% CI 1.06–1.29, p = 0.002) after adjusting for age, ethnicity, Gleason score, T stage, margin status, initial PSA, and treatment arm ( 61 ). The 4Kscore blood test can also be mentioned, awaiting its Clinical Laboratory Improvement Amendment (CLIA) accreditation.…”

Risikoermittlung beim Prostatakarzinom

“…352 Proben erfüllten alle Qualitätskriterien. Jeweils 176 Männer erhielten Bicalutamid und Placebo [1].…”