A 22-genomic classifier (the Decipher score) was able to predict the course of disease in men with high-risk prostate cancer, according to a patient-level meta-analysis of three randomized clinical trials presented at the 2021 American Society for Radiation Oncology (ASTRO) Annual Meeting.1 Use of this genomic classifier (GC) score has the potential to personalize treatment for men with high-risk prostate cancer by identifying appropriate candidates for deintensification vs intensification of therapy.
This is reportedly the first study to validate a genetic biomarker using archived tissue samples obtained before treatment at the time of diagnosis within a phase III trial of high-risk prostate cancer. The Decipher score was previously validated as a prognostic biomarker after treatment following radical prostatectomy.
Two-thirds of prostate cancer deaths occur in men with high-risk disease. Standard therapy for this group of patients is irradiation plus 2 years of androgen-deprivation therapy, which has been associated with side effects that may compromise quality of life (eg, loss of libido, hot flashes, and potential cardiovascular and cognitive changes). The hope is that a biomarker (such as GC) may be used to develop treatment guidelines based on patients suited for more intensive therapy and those who can be treated with less intensive therapy, for example, 1 year of androgen-deprivation therapy instead of the standard 2 years.
Paul L. Nguyen, MD
“We have been using a ‘one-size-fits-all’ approach to treat high-risk prostate cancer. Use of genomic testing to stratify patients at higher and lower risk of developing metastasis may allow for personalization of therapy for patients with prostate cancer, which is where we want the field to go,” said lead presenter Paul L. Nguyen, MD, Professor at Harvard Medical School and Vice Chair for Clinical Research in the Department of Radiology at Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston.
Details and Key Findings of Meta-analysis
The meta-analysis Dr. Nguyen presented was based on archived pretreatment biopsy samples of the highest-grade tumors from participants in three major prostate cancer trials: RTOG 9202, RTOG 9413, and RTOG 9902. It involved a total of 385 samples from individuals enrolled in those trials. Of these samples, 69% passed microarray quality control, and the median follow-up was 11 years. “Some of these samples were 29 years old,” Dr. Nguyen remarked.
The investigators used the Decipher biopsy test, which analyzes the activity of 22 genes involved in prostate tumors, to develop a GC score reflecting the aggressiveness of each patient’s tumor. They then determined the association of the GC scores with long-term outcomes.
“We found that the genomic classifier was highly prognostic for distant metastasis, prostate cancer–specific survival, and overall survival,” he stated. “This was true for each of the three randomized trials.”
In a multivariate analysis adjusted for confounding variables that included age, prostate-specific antigen, Gleason score, tumor stage, trial, and randomized treatment arm, the GC score remained prognostic for distant metastasis, prostate cancer–specific survival, and overall survival “across the board,” Dr. Nguyen said. For example, the rate of distant metastasis at 10 years was 29% for those with an intermediate/high GC score (ie, ≥ 0.45) compared with 13% for those with a low GC score.
“The genomic classifier score is the only factor that consistently stays significantly associated with distant metastasis, prostate cancer–specific survival, and overall survival,” Dr. Nguyen told the ASTRO audience. “It trumps all the other factors predicting outcome, including the Gleason score.”
Dr. Nguyen continued: “This is the first validation study of any biopsy-based genomic classifier from prospective randomized trials of high-risk prostate cancer. We know high-risk prostate cancer is a heterogeneous disease. The genomic classifier score may personalize the treatment approach.”
The next step, according to Dr. Nguyen, is a phase III trial—NRG-GU009/PREDICT-RT, and he encouraged the audience to enroll patients.
“PREDICT-RT is the first prospective trial of high-risk prostate cancer to use the genomic classifier score to decide upon intensification or deintensification of therapy. This is an important step required before this score can be used to personalize therapy in the clinic. We want patients with higher scores who need intensive therapy to get it; for those with a lower genomic classifier score, we hope to deintensify hormone therapy from 24 to 12 months,” he said.
DISCLOSURE: Dr. Nguyen has received research grants from Janssen, Astellas, and Bayer; has received honoraria from Bayer and Janssen; has served as a consultant to Infinity Pharmaceuticals, GI Windows, Astellas, Augmenix, Janssen, Boston Scientific, COTA, and Myovant Sciences; has served on the advisory board for Ferring Pharmaceuticals, Medivation, Dendreon, Astellas, Bayer, and Blue Earth.
1. Nguyen PL, et al: Validation of a 22-gene genomic classifier in the NRG Oncology/RTOG 9202, 9413, and 9902 phase III randomized trials. 2021 ASTRO Annual Meeting. Abstract 95. Presented October 25, 2021.
“Regarding Dr. Nguyen’s study, genomic classifiers are here. They are the future of our field for personalized prostate cancer therapy,” stated Sophia C. Kamran, MD, Assistant Professor of Radiation Oncology at Massachusetts General Hospital, speaking at a press conference where this abstract was...