ANZUP’s TheraP trial has found that certain ‘spelling mistakes’ in prostate cancer DNA found in the blood can reveal hidden weaknesses that make the cancer easier to target with specific treatments.
Led by Dr Edmond Kwan, clinician-scientist and medical oncologist from Eastern Health Clinical School and the Monash Biomedicine Discovery Institute, in partnership with Associate Professor Alexander Wyatt and senior scientists from the Vancouver Prostate Centre, the study published in Nature Medicine shows that patients with lower levels of circulating tumour DNA (ctDNA) – fragments of tumour DNA circulating in the bloodstream – responded significantly better to treatment with an innovative intravenous therapy called Lutetium PSMA than to patients receiving best standard treatment with chemotherapy.
The results were determined in the TheraP clinical trial, designed and conducted by ANZUP, involving 200 participants.
The study is the first to show that a blood test can help predict how well an advanced prostate cancer will respond to Lutetium PSMA, offering a simpler, more accessible way to support treatment decisions alongside the specialised PET scans doctors currently rely on.
Dr Kwan said that the blood test will help doctors and patients make more informed, personalised treatment decisions based on real-time insights into the cancer. “Unlike traditional approaches that rely on tissue biopsies, blood tests offer a contemporary, non-invasive snapshot of what’s happening in a patient’s body now, shaped by the cancer’s evolution in response to previous therapies,” he said.
“This new approach could allow doctors and patients to select treatments that are more appropriate for a particular person, and reduce unnecessary exposure to side effects from a treatment less likely to give benefit. That is particularly important for patients from regional and rural areas, where Lutetium PSMA treatment may not be readily available and access might be difficult.”
Lutetium PSMA targets a specific protein abundant on the surface of prostate cancer cells and delivers lethal doses of radiation. Using a specialised blood test, the research team showed that prostate cancer mutations can be detected through fragments of tumour DNA circulating in the bloodstream, allowing doctors to identify them without needing invasive tissue biopsies.
While detection of mutations is one piece of the puzzle, another challenge is knowing which patients are most likely to benefit from Lutetium PSMA or other treatments like chemotherapy. These options are increasingly becoming available for Australians with prostate cancer, but doctors and patients face a difficult choice in choosing the right treatment for each individual.
Therapies are costly, side effects can sometimes be significant, there might be a limited period when people can safely get a certain treatment, and access is limited, especially outside major cities.
Professor Ian Davis, ANZUP Chair and joint senior author of the TheraP trial, said that the discovery could reshape the future treatment of prostate cancer. “A simple tool like this to help people choose the best treatment options for their cancer will reduce trial-and-error decision-making, improve the chance of optimal sequencing of treatments, and preserve scarce resources,” he said.
“Ultimately, we hope this clinical trial result leads to better outcomes for the estimated 72 Australians who are diagnosed with prostate cancer every day, and for the millions affected globally.”
Read ‘Lutetium-177–PSMA-617 or cabazitaxel in metastatic prostate cancer: circulating tumor DNA analysis of the randomized phase 2 TheraP trial’ here.