Grant: Project Grant

When prostate cancer spreads to other organs, patients receive treatments that aim to extend life by shrinking the cancer. However, not all patients benefit, and these treatments can be costly and cause side effects. It is therefore important to detect early if a treatment is not working. In prostate cancer, monitoring relies on prostate specific antigen (PSA) tests and bone scans, but these can be inaccurate especially in the first few months of therapy. Our team of prostate cancer oncology and genetics experts have pioneered ways to analyze cancer genetic material shed into the blood, called circulating tumor DNA (ctDNA). We have shown that ctDNA levels in a blood sample reflect cancer size and aggression. Emerging research suggests that measuring ctDNA early during treatment may reveal whether the cancer is shrinking. The critical next steps are to determine the exact ctDNA change that signals a true treatment response, and the best time to measure it. Here, we will study a unique resource of pre- and on-treatment blood samples from 1800 patients with metastatic prostate cancer who received chemotherapy, hormonal therapy, radioligand therapy, or targeted therapy. This will allow us to define the precise ctDNA change linked to benefit for therapy type. For some patients, we are collecting blood at multiple time points during the initial weeks of treatment to find the earliest time at which a ctDNA test can accurately predict durable patient benefit from therapy. We will also assess whether patient factors such as medications or other health conditions affect test reliability. By the end of this 4-year project, we will deliver validated ctDNA thresholds and sampling strategies that can be implemented in clinical trials. This will enable earlier, more accurate assessment of treatment success or failure, reducing patient exposure to ineffective therapies and guiding timely switches to better options.