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Radiation Oncology Perspective

The Radiation Oncology Perspective: Genomic vs Genetic Testing in Prostate Cancer



A Frontline Forum hosted by CancerNetwork during the 2025 American College of Radiation Oncology Summit in March focused on gene expression testing options for patients with prostate cancer.

The discussion centered on genetic vs genomic testing, current NCCN guidelines, and decisions based on which testing options to use. Following the program, CancerNetwork spoke with leading clinicians in the radiation oncology space regarding the use of these tests, androgen deprivation therapy (ADT), and the thought process for selecting patients for active surveillance.

To begin, the distinction between a genomic biomarker vs germline testing was mentioned. A genomic biomarker includes a measurable DNA or RNA characteristic that can be used to indicate normal biological processes, disease, or response to treatment. Germline testing is the analysis of DNA to identify genetic variations that may be associated with health risks or cancer predisposition.

Decipher Prostate has a level 1B evidence rating among the NCCN guidelines. A news release from the developer stated that Decipher received the rating because of evidence from the postbiopsy and postprostatectomy settings.

Decipher Prostate is a 22-gene test incorporating RNA whole-transcriptome analysis plus machine learning to help inform treatment decisions for patients with prostate cancer. Biopsy or surgically resected samples are used to provide a patient’s risk for developing metastases with standard treatment. This information will better personalize care as well as provide options that are less treatment-intensive. Validation for this test comes from more than 75 studies and more than 100,000 patients.

The Oncotype DX test is a 17-gene assay that was created to assess 12 cancer-related genes and 5 reference genes through biopsy tissue.

A recent study looking into genomic classifiers across 10 studies reported the risk reclassification. In studies that had a low risk of bias and patients with prostate cancer who were very low or low risk, patients were more likely to have their risk levels classified as the same or lower with Oncotype DX at 100% to 88.1%, Decipher at 87.2% to 82.9%, and Prolaris at 76.9%. There was, however, 1 randomized trial of genomic classifiers with Oncotype DX that reclassified 34.5% of patients who were very low risk and 29.4% who were low risk to the high-risk category.

The study takeaway mentioned a need for more trials to better determine the role of genomic classifiers for patients with newly diagnosed prostate cancer who are considering first-line treatment.

The NCCN guidelines include Prolaris in the prostate cancer guidelines with category level 2A of evidence. This is a molecular diagnostic test that can provide personalized information regarding the aggressiveness of a tumor and can determine whether a patient should pursue treatment. Of note, a news release from Myriad Genetics stated that it is the only biomarker test to quantify the benefits of ADT to radiation therapy.

Findings from a study by Tward et al found the combined clinical cell-cycle risk (CCR) score for a single therapy that is a continuous variable was able to prognosticate metastases (HR, 3.97; 95% CI, 2.61-6.06) as well as for the dichotomized threshold (HR, 15.90; 95% CI, 5.43-46.52).5 If patients were given single-modality therapy of radiation therapy or surgery, the 10-year Kaplan Meier score was 4.3% (95% CI, 1.0%-17.1%) for those with a CCR score below the threshold and 20.4% (95% CI, 13.2%-30.7%) for those with a score above the threshold.

The authors stated that if the CCR score was below the 2.112 multimodality threshold, patients could safely avoid multimodality therapy. Additionally, clinicians can use the CCR scores to counsel patients on which type of therapy would be most effective for intermediate or high-risk prostate cancer.

A discussion during the program also occurred around clinical decision-making. The program also focused on active surveillance, which is used to identify appropriate candidates who are eligible for this treatment with favorable or intermediate disease; treatment modality selection included guiding choices between single and multimodality approaches; and ADT optimization was determining if there was a benefit by adding ADT to radiation therapy.

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