Grant: Project Grant

In 2020, 23,300 people were diagnosed with prostate cancer (PCa) in Canada. Despite medical and surgical interventions, 1 in 4 will die from the disease. Approximately 25% of advanced PCa patients have alterations in genes that normally repair damage to other genes. The genes that do the repair are called DNA damage response (DDR) genes. Genetic abnormalities in those genes make cancer cells sensitive to a form of chemotherapy called platinum-based chemotherapy (PBC). PBC, however, is not typically used to treat PCa because older studies-before there were screening tests for DDR genes-did not find it effective in treating PCa. Instead, the common chemotherapy agent used to treat advanced PCa is a non-platinum-based drug called docetaxel. A few recent studies have shown some benefit in using PBC to treat PCa with DDR gene alterations. In fact, some clinicians are already using PBC combined or in sequence with docetaxel despite the lack of good evidence that it benefits patients. In the past, genetic testing for DDR gene alterations was not routinely done in Canada. Health Canada recently approved the use of a drug to treat cancer in patients with specific DDR gene alterations because this drug improves survival (though not curative). This has resulted in widespread testing for DDR gene alterations in prostate cancer patients. We propose a study to identify the benefits and risks of using PBC combined with docetaxel to treat PCa in patients with DDR gene alterations compared to docetaxel alone. PBC is relatively inexpensive and, when used in combination with docetaxel, should not add significantly to healthcare costs. The study will specifically test whether PBC used in combination with docetaxel improves overall survival for advanced PCa patients with DDR gene alterations. If this study shows a positive benefit for those patients, it could change how PCa is treated in a way that could help extend the lives of a quarter of all advanced PCa patients.