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22-Gene Classifier Score May Allow for Personalization of Therapy in Patients With High-Risk Prostate Cancer


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A 22-gene genomic classifier (the Decipher score) may be 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 by Paul L. Nguyen, MD, at the 2021 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 95). Use of this genomic assay has the potential to personalize treatment for men with high-risk prostate cancer by identifying appropriate candidates for de-intensification vs intensification of therapy.

This is the first study to validate a genetic biomarker using archived tissue samples obtained pretreatment at the time of diagnosis. Decipher was previously validated as a prognostic biomarker after radical prostatectomy.

Paul L. Nguyen, MD

Paul L. Nguyen, MD

Two-thirds of deaths due to prostate cancer occur in men with high-risk disease. Standard therapy for this group of patients is radiation plus 2 years of androgen-deprivation therapy (ADT). ADT has side effects that can compromise quality of life, including loss of libido, hot flashes, and potential cardiovascular and cognitive changes. The hope is that a biomarker (such as the genomic classifier) could help develop treatment guidelines for which patients should receive more intensive therapy vs less intensive therapy—for example, 1 year of ADT instead of the standard 2 years.

“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 could allow for personalization of therapy for patients with prostate cancer, which is where we want the field to go,” said lead presenter Dr. Nguyen, 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 in Boston.

Meta-analysis Details

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. The meta-analysis involved a total of 385 samples from individuals enrolled in those trials. Of these, 69% passed microarray quality control; median follow-up was 11 years.

“Some of these samples were 29 years old,” Dr. Nguyen noted.

The investigators used the Decipher biopsy test, which analyzes the activity of 22 genes involved in prostate tumors, to develop a score reflecting the aggressiveness of each patient’s tumor. Then they determined the association of the Decipher scores with long-term outcomes.

Effectiveness of Decipher

“We found that the genomic classifier was highly prognostic for distant metastasis, prostate cancer–specific survival, and overall survival,” Dr. Nguyen stated. “This was true for each of the three randomized trials.”

We found that the genomic classifier was highly prognostic for distant metastasis, prostate cancer–specific survival, and overall survival...This was true for each of the three randomized trials.
— Paul L. Nguyen, MD

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In a multivariate analysis adjusted for confounding variables that included age, prostate-specific antigen, Gleason score, tumor stage, trial, and randomized treatment arm, the genomic classifier was still prognostic for distant metastasis, prostate cancer­–specific survival, and overall survival “across the board,” he said.

For example, the rate of distant metastasis at 10 years was 29% for those with intermediate/high genetic classifier scores (ie, genomic classifier score > 0.45) compared to 13% for those with a low genetic classifier score.

“The genomic classifier score is the only factor that stays significantly associated with distant metastasis, prostate cancer–specific survival, and overall survival. It trumps all the other factors predicting outcome, including the Gleason score,” Dr. Nguyen told the audience.

“This is the first validation study of any genomic classifier from prospective randomized trials. We know high-risk prostate cancer is a heterogeneous disease. The genetic classifier score can personalize the treatment approach,” he said.

Dr. Nguyen said the next step is a phase III trial—NRG-GU009/PREDICT-RT—and he encouraged the audience to enroll patients.

“This is first prospective trial to use the genetic classifier score to decide upon intensification or deintensification of therapy. This is an important step required to using this score in the clinic. We want patients who need intensive therapy to get it, and for those with a lower genetic classifier score, we hope to de-intensify hormone therapy from 24 months to just 12 months,” he said.

Disclosure: For full disclosures of the study authors, visit redjournal.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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