Int J Radiat Oncol Biol Phys. 2023 May 1:S0360-3016(23)00371-1. doi: 10.1016/j.ijrobp.2023.04.010. Online ahead of print.
ABSTRACT
BACKGROUND/PURPOSE: Intermediate-risk prostate cancer is a heterogeneous disease state with diverse treatment options. The 22-gene Decipher genomic classifier (GC) retrospectively has shown to improve risk stratification in these patients. Herein, we assess the performance of the GC in men with intermediate-risk disease enrolled on xxxx with updated follow-up.
METHODS: After National Cancer Institute approval, biopsy slides were collected from xxxx, a randomized phase III trial of men with intermediate-risk prostate cancer randomized to 70.2 Gy vs 79.2 Gy of radiotherapy without androgen deprivation therapy. RNA was extracted from the highest-grade tumor foci to generate the locked 22-gene GC model. The primary endpoint for this ancillary project was disease progression (composite of biochemical-, local-failure, distant metastasis, prostate cancer-specific mortality, and use of salvage therapy). Individual endpoints were also assessed. Fine-Gray or cause-specific Cox multivariable models were constructed adjusting for randomization arm and trial stratification factors.
RESULTS: Two-hundred and fifteen patient samples passed quality control for analysis. The median follow-up was 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] 1.12, 95%CI 1.00-1.26, p=0.04), biochemical failure (sHR 1.22, 95%CI 1.10-1.37, p<0.001), distant metastasis (sHR 1.28, 95%CI 1.06-1.55, p=0.01), and PCSM (sHR 1.45, 95%CI 1.20-1.76, p<0.001). 10-year distant metastasis in GC low patients was 4% compared to 16% for GC high risk patients. In patients with lower GC scores, the 10-year difference in metastasis-free survival rate between arms was -7%, compared to 21% for higher GC patients (p-interaction 0.04).
CONCLUSIONS: This study represents the first validation of a biopsy-based gene expression classifier, assessing both its prognostic and predictive value, using data from a randomized phase III trial of intermediate-risk prostate cancer. Decipher improves risk stratification and can aid in treatment decision-making in men with intermediate-risk disease.
PMID:37137444 | DOI:10.1016/j.ijrobp.2023.04.010
