Improving Prostate Cancer Diagnosis and Management in the Yukon
John Lewis, University of Alberta
Lead Investigator Bio:
John Lewis holds the Frank and Carla Sojonky Chair in Prostate Cancer Research at the University of Alberta. He is a Professor in the Department of Oncology and chairs the Alberta Prostate Cancer Research Initiative. As an entrepreneur, Dr. Lewis has also founded three Canadian biotechnology companies. Dr. John Lewis’s laboratory studies prostate cancer, the most commonly diagnosed cancer in Canadian men. Since no man dies of prostate cancer that stays in his prostate, the group uses real-time intravital imaging of the tumour microenvironment to learn about the mechanisms of cancer metastasis, including the invasion, intravasation and extravasation steps that lead to metastatic dissemination. The group has used this approach to identify key drivers of metastatic progression in prostate and other cancers, and is leveraging this information to develop non-invasive tests to detect aggressive prostate cancer and to develop novel nanoparticles to block the spread of prostate cancer.
Prostate cancer is the most commonly diagnosed cancer and the third leading cause of cancer deaths in men. In the Yukon, men with elevated PSA tests who are suspected for prostate cancer are currently referred to a Urologist in BC or Alberta for a prostate biopsy. Up to half of these men ultimately do not have prostate cancer and up to 90% have clinically insignificant prostate cancer, resulting in substantial travel and healthcare costs. In this project, we will utilize a recently developed blood test called EV-FPS to assess whether it could be used to help select patients more effectively for prostate biopsy. This should provide more reliable information about how dangerous a patient’s cancer is so that resources are allocated to those who most need it.
The current screening and diagnosis regime for prostate cancer in the Yukon does not serve men well due to the requirement to travel to Alberta or British Columbia for a prostate biopsy. Current screening for PCa is done mainly by digital rectal examination (DRE) and serum prostate-specific antigen (PSA) measurement. If these tests are abnormal, the patient is then referred for a prostate biopsy, which requires extensive travel. Unfortunately, most biopsies show no cancer and yet subject the patient to anxiety and risks of biopsy including sepsis requiring hospitalization. Given the logistics of prostate cancer screening and diagnosis in the Yukon, there is an immediate need for improved diagnostics to reduce unnecessary biopsies and over-diagnosis of indolent disease. To address this, we have recently developed a robust blood-based assay called the extracellular vesicle fingerprint score (EV-FPS) to predict the outcome of a prostate biopsy. We have completed an initial clinical validation of EV-FPS in a prospective cohort of 377 Albertan men for whom a prostate biopsy was ordered. EV-FPS was significantly higher in aggressive vs. indolent prostate cancer. At a sensitivity of 95%, clinical features including PSA provided only 17% specificity for aggressive prostate cancer with an AUC of 0.72. Combining EV-FPS with clinical features at sensitivity 95% increased the specificity for aggressive prostate cancer to 56% with an AUC of 0.84. Using a score cut-off that achieves 95% sensitivity, our decision curve analysis suggest that up to 40% of men could use this information to potentially avoid a biopsy. In this study, we will incorporate the Yukon PSA screening population into our clinical validation efforts with AHS and DynaLIFE. Once the performance of EV-FPS is validated propectively in this environment, it can be incorporated into clinical care in the Yukon. This will have a significant impact on the efficiency of screening activities in the territory.
Impact on prostate cancer patients:
The potential impact is considerable; Many men in the Yukon are forced to travel long distances to obtain a prostate biopsy even though the majority are negative or detect clinically insignificant cancers. Successful implementation could eventually eliminate up to 600,000 unnecessary biopsies, 24,000 hospitalizations and up to 50% of unnecessary treatments for prostate cancer in North America alone. Beyond an estimated cost savings to the healthcare system of more than $1.4B per year, this will have a dramatic impact on the healthcare experience and quality of life for men.