Genomic testing helps inform treatment intensity decisions in intermediate-risk prostate cancer

Data from a large, real-world analysis presented at the American Society for Radiation Oncology (ASTRO) 67th Annual Meeting¹ suggest that treatment can be deintensified for many patients with intermediate-risk prostate cancer. Drawing on genomic biomarker test results across more than 60,000 patients, the study highlights how genetic testing can refine risk stratification and guide decisions between active surveillance, single-modality therapy, and intensified multimodal approaches.

In total, the study included more than 60,000 patients with either National Comprehensive Cancer Network favorable intermediate-risk or unfavorable intermediate-risk disease who had clinical pretreatment and biomarker data from a 31-gene cell cycle progression test. Data were obtained from the Myriad Collaborative Research Registry.

Of the 31,935 patients with favorable intermediate-risk disease, 58.2% were recommended to deintensify treatment and pursue active surveillance, 41.5% for single-modal therapy, and less than 1% to intensify treatment to multimodal therapy. Among the 28,487 patients with unfavorable intermediate-risk disease, 11.9% were recommended for active surveillance, 67.6% for single-modal therapy, and 20.5% for multimodal therapy.

Patients with favorable intermediate-risk disease had an estimated 10-year risk of metastasis ranging from 0.2% to 26.5%. For patients with unfavorable intermediate-risk disease, the estimated risk ranged from 0.2% to 66.7%. In patients with unfavorable intermediate-risk disease recommended for multimodal therapy, adding androgen deprivation therapy (ADT) to radiation led to an estimated absolute reduction in the risk of 10-year metastasis ranging from 3.7% to 19.2%.

In the following interview with Urology Times, presenting author Christopher Lee, MD, breaks down this study's implications and future directions. Lee is a radiation oncologist at Cancer Care Northwest in Spokane Valley, Washington.

Could you describe the background and rationale for this study?

Genomic and genetic testing are utilized more each year across many cancer subtypes. Of course, when we sit across from patients, we want to give them the best options. The benefit of having some of these genetic and biomarker tests is that they help give us independent risk information for our patients based on their individual cancer specimen. In our practice, we utilize biomarker testing frequently to help us guide patients to the correct type of treatment and to help us and patients have peace of mind that we have as much information as possible to make those critical decisions.

In this study, we looked at an extensive registry of patients who [underwent] genetic and genomic testing. The Myriad [Collaborative Research Registry] includes more than 1.3 million patients. For this study specifically, we focused on a group of patients with prostate cancer who had intermediate-risk disease, either favorable intermediate-risk disease or unfavorable intermediate-risk disease. That was more than 60,000 patients. The exciting part of this is that there are huge numbers here, and it helps us to better understand patterns of care. It helps us to understand patients' clinical features as they go into these treatment decisions.

We looked at the predicted statistics for these patients for the risk of metastasis for these different groups and looked at recommendations. This helped us to understand, in larger cohorts with risk classification, some of those absolute risk reduction numbers for a large subset of these unfavorable intermediate-risk and favorable intermediate-risk patients with prostate cancer.

What were the key findings presented at ASTRO?

Our key findings are No. 1, accurate risk classification and the ability to determine the absolute risk reduction for patients are crucial for us to [make] informed decisions regarding the intensity of the treatment we give. For a radiation oncologist, when I'm sitting in front of patients, it's often the question of No. 1: Does the patient need treatment? And No. 2: If they're getting radiation treatment, should we add hormone therapy? This test can be very helpful in making those decisions and helping us understand whether patients can be on an active surveillance paradigm or whether they need more intensive treatment by adding ADT to the radiation.

I think it's also [important] to highlight that having access to this large, real-world clinical and genetic data allows us to study patterns of clinical disease presentation, and it also helps us to gain insights into personalized risk for patients. Again, as we seek to provide a customized and personalized treatment approach for each patient, having these biomarker tests helps us better risk-stratify and make better-informed decisions with our patients. [It also allows us] to give them statistics such as the absolute reduction on the risk of metastasis to help make a final decision and have peace of mind in making that final decision.

As a radiation oncologist, how do you collaborate with urologists when genomic test results suggest deintensification or intensification for these patients?

Of course, patients with prostate cancer often require a multidisciplinary team. We work with urologists and medical oncologists, and often, these are joint decisions. In my clinic, for example, these tests are often ordered before the patient even arrives to help make decisions regarding whether the patient is an active surveillance candidate or whether the patient should proceed with treatment. I think the usefulness of these tests has become critical to decision-making for patients in many different risk groups.

Is there any future work planned based on the findings from this study?

As far as future research, there are many unanswered questions that in the future will be able to be better answered through genetic testing and biomarker testing. This is an exciting area of research to be in, not just in prostate cancer, but in all cancer tumor types. There's an excitement to better risk-stratify and understand the aggressiveness of the biology, because every patient with prostate cancer doesn't have the same biology of prostate cancer. We want to [be] informed [about patients’] cancer biology so we can provide treatment recommendations that best fit their situation.

Is there anything else that you’d like to add?

Access to large patient databases such as this is critical to answering future research questions. This type of database offers clinicians and researchers an opportunity to study patterns of clinical disease presentation and gain insights into personalized risk for patient care.

REFERENCE

1. Lee CM. Genomic tumor testing in NCCN favorable and unfavorable intermediate-risk prostate cancer informs treatment intensity: data from an open access research registry. Presented at: American Society of Radiation Oncology 67th Annual Meeting; September 27-October 1, 2025; San Francisco, CA. Abstract 3266.