ASCO GU 2022: Validation of the Performance of the Decipher Biopsy Genomic Classifier in Intermediate-Risk Prostate Cancer in the Phase III Randomized Trial NRG Oncology/RTOG 0126

( On the first day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022, Poster Session A focussed on the care of patients with prostate cancer. Dr. Dan Spratt presented a poster outlining validation of the Decipher biopsy genomic classifier in intermediate-risk prostate cancer. The 22-gene Decipher genomic classifier (GC) is a prognostic biomarker that has been validated in phase III trials in high-risk localized, post-prostatectomy, and metastatic and non-metastatic castration-resistant prostate cancer.

In this study, the authors used the phase III randomized trial NRG/RTOG 0126 trial to provide the first validation of the biopsy GC in intermediate-risk prostate cancer. Following National Cancer Institute approval, the authors obtained biopsy slides from the NRG biobank from RTOG 0126. RTOG 0126 is a phase III randomized trial of men with intermediate-risk prostate cancer who were randomized to 70.2 Gy versus 79.2 Gy of radiotherapy without the use of concomitant hormone therapy.

The authors extracted RNA from the highest grade tumor foci and processed this through a quality control (QC) pipeline prior to generation of the previously locked 22-gene GC model. After GC data was generated, it was linked with clinical outcomes to assess the prognostic performance of the Decipher assay. The primary endpoint for this ancillary project was disease progression, defined as biochemical failure, local failure, distant metastasis or prostate cancer-specific mortality, as well as use of salvage therapy. Secondarily the authors assessed the previous individual endpoints, metastasis-free survival, and overall survival. Independent Decipher GC prognostic performance was assessed using cause-specific Cox or competing risk adjusted Fine-Gray multivariable models that included randomization arm and prognostic stratification factors. Death without events were treated as competing risks.

Among the 449 patient samples that had suitable cDNA for expression analysis, 215 passed quality control. Of these patients, 61% had Gleason 3+4, 24% had Gleason 4+3, and the median PSA was 7.2 ng/mL (IQR 5.0-10.2). Patients were followed for a median of 12.8 years (range 2.4-17.7).

On multivariable analysis the 22-gene GC (per 0.1 unit) was independently prognostic for disease progression (subdistribution hazard ratio [sHR] 1.13, 95%CI (1.01-1.26), p = 0.03), biochemical failure (sHR 1.23, 95%CI 1.10-1.37, p < 0.001), distant metastasis (sHR 1.28, 95%CI 1.06-1.54, p = 0.01), and PCSM (sHR 1.45, 95%CI 1.20-1.76, p < 0.001).

Cumulative incidence (or 1-cumulative incidence) estimates of GC low (<0.45), intermediate (0.45-0.6), and high (>0.6) risk groups for (A) BF Phoenix, (B) BF ASTRO, (C) receipt of salvage therapy, (D) disease progression, (E) distant metastasis, (F) MFS, (G) PCSM, and (H) overall survival.

Further, dichotomization of the Decipher GC scores into low and intermediate-high risk groups provided clinically meaningful differences in nearly all outcome metrics. For example, 10-year distant metastasis rates differed from 5% among those with Decipher low to 26% among those with Decipher intermediate-high scores.

Further, the authors demonstrated a predictive ability for GC with a greater benefit of radiotherapy dose escalation seen among patients with higher GC scores.

The authors therefore conclude that this, the first validation of any biopsy-based gene expression classifier in intermediate-risk prostate cancer, demonstrates that Decipher is independently prognostic and can identify patients that have low rates of metastatic events despite not receiving concurrent hormone therapy, and can be used to help personalize care.

Presented by: Daniel Eidelberg Spratt MD, University Hospitals Seidman Cancer Center, Cleveland, OH