A blood test could help identify men with advanced prostate cancer most likely to benefit from targeted radiotherapy

by Institute of Cancer Research

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A blood test could help identify men with advanced prostate cancer who are more likely to experience longer disease control following targeted radiotherapy, according to research led by The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, London and University College London. The findings are published in the journal JAMA Network Open.

New analysis from the TRAP trial found that measuring circulating tumor DNA (ctDNA) in the blood before treatment could provide additional information about how a patient's cancer may respond to radiotherapy.

CtDNA consists of small fragments of genetic material released by cancer cells into the bloodstream. Analyzing these fragments can help researchers detect signs of cancer activity that are not apparent on scans.

The TRAP trial investigated the use of stereotactic body radiotherapy (SBRT) in patients with hormone-resistant oligoprogressive prostate cancer. Oligoprogressive cancer occurs when cells from the original tumor travel within the body but are only active at fewer than three sites, forming new tumors or lesions. The men on the trial received radiotherapy to these areas while continuing their existing hormone therapies, such as abiraterone or enzalutamide.

An advanced form of radiotherapy

However, cancer may also be growing in areas too small to be detected by scans, and not all patients experience the same duration of cancer control following radiotherapy. A blood test could help researchers better understand these differences and investigate which patients may be most suitable for this treatment.

Stereotactic body radiotherapy (SBRT) is an advanced form of radiotherapy that delivers highly focused radiation to tumors. In men whose prostate cancer is progressing in a small number of areas, it can target these sites while allowing them to continue their existing hormone-based treatment.

The research team analyzed blood samples collected before radiotherapy from 77 men participating in the TRAP trial. The patients were monitored for more than two years. Of these men, 19 had detectable ctDNA before radiotherapy, while 58 had no detectable ctDNA.

Could ctDNA guide treatment decisions?

Men with no detectable ctDNA experienced significantly longer progression-free survival following radiotherapy than those with detectable ctDNA. Median time without disease progression was 7.8 months for men with no detectable ctDNA, compared with three months for those with detectable ctDNA.

Six months after treatment, around 58% of men whose blood samples were negative for ctDNA remained free from disease progression, compared with 21% of men who tested positive.

The association remained significant after the researchers accounted for other clinical factors, including age, prostate-specific antigen (PSA) levels, previous chemotherapy and the location of the treated tumor.

The findings could help inform future studies investigating whether ctDNA testing can guide treatment decisions for men with advanced prostate cancer.

Men with no detectable ctDNA may be more likely to experience longer disease control after radiotherapy to the visible areas of progression. In contrast, detectable ctDNA could indicate that cancer remains active elsewhere in the body, potentially helping researchers investigate when alternative treatment may be needed.

Combining test results with imaging

By combining blood-test results with imaging and other clinical information, researchers hope to develop a clearer understanding of how advanced prostate cancer progresses and how best to tailor treatment to individual patients.

Alison Tree, consultant clinical oncologist at The Royal Marsden NHS Foundation Trust, honorary reader at The Institute of Cancer Research and chief investigator of the TRAP trial, said, "These findings suggest that a simple blood test could give us valuable additional information about how advanced prostate cancer is behaving, beyond what we can see on scans. We found that men with no detectable ctDNA before radiotherapy tended to have longer periods without their cancer progressing than those with detectable levels.

"Although more research is needed before this test can be used to guide treatment decisions, our findings are an important step toward understanding which patients may benefit most from targeted radiotherapy and how we could better personalize treatment for men with advanced prostate cancer."

Dr. Alison Reid, consultant medical oncologist at The Royal Marsden NHS Foundation Trust and first author of the trial, said, "Having a blood-based marker that aids us in determining for whom this is an appropriate approach is extremely helpful. It allows those that will benefit to continue abiraterone and enzalutamide and have SBRT alongside, whereas for others, the right approach might be to move on to a new medication for their prostate cancer."

Royal Marsden patient Tony Sparrow, 73, was first diagnosed with bladder cancer in 2014 and received treatment to bring the disease under control.

As part of his ongoing monitoring, in 2019, a biopsy discovered that he had advanced prostate cancer and he was referred to The Royal Marsden for surgery to remove both his prostate and bladder.

Further tests found that the prostate cancer had metastasized to his hip, spine and groin.

Sparrow, from Epsom, underwent radiotherapy and then was invited to join the TRAP trial and underwent SBRT.

He said, "The SBRT radiotherapy process was absolutely fine. Just 10 minutes a session, completely painless and most importantly it did the trick—afterward there was nothing on the scan. There weren't really any side effects either."

Publication details

Alison Reid et al., Circulating Tumor DNA in Oligoprogressive Prostate Cancer Treated With Stereotactic Radiotherapy, JAMA Network Open (2026). DOI: 10.1001/jamanetworkopen.2026.43400

Journal information: JAMA Network Open

Key medical concepts

Circulating Tumor DNAProgression-Free SurvivalRadiotherapy, Stereotactic Body

Clinical categories

OncologyUrologyMen's health Provided by Institute of Cancer Research Who's behind this story?

Gaby Clark

MA in English, copy editor since 2021 with experience in higher education and health content. Dedicated to trustworthy science news. Full profile →

Robert Egan

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