New genetic test predicts risk of prostate cancer returning

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A group of Canadian researchers have developed a new genetic test that accurately predicts the risk of coming back after treatment and identifies patients who would benefit from additional therapy. The test is unique because it uses the genomic profile of the tumour and the oxygen content of the area around the tumour to determine the risk of relapse. The study, which was recently published in the journal The Lancet Oncology, tackles an important challenge in treating prostate cancer.

“The problem we wanted to solve was to find a way to avoid over-treatment in men with slow-moving cancers and identify the patients with aggressive disease who would fail treatment,” says the study’s lead author Ms. Emilie Lalonde, a PhD candidate at the Ontario Institute for Cancer Research (OICR). “This is the first time that tumour genomics and oxygen-content have been linked together to predict patient outcomes.”

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To develop the test the researchers looked back at the DNA of two groups of patients with low to intermediate risk prostate cancer – those who were treated with image-guided radiotherapy and those who had surgery to remove their tumours. The genetic test was made more robust when the oxygen content of the tumour was considered in the analysis. Low levels of oxygen in tumours, known as tumour hypoxia, had been previously linked on its own as a potential way to predict the spread of prostate cancer.

“What was really interesting was that when we brought in information on the oxygen content of the tumours we found that this impact was independent of the genomics and if you considered the two together the effect was compounded, essentially,” says Lalonde. “That was actually pretty surprising because we knew that they both had predictive value alone and we thought that the same patients were affected by both processes, but we found that not to be the case.”

The study was supervised by Drs. Paul Boutros of OICR and Robert Bristow of the University Health Network’s Princess Margaret Cancer Centre. Boutros and Bristow are investigators in the Canadian Prostate Cancer Genome Network (CPC-GENE), which is working to ‘crack’ the genetic code of prostate cancer to predict treatment failure for immediate risk prostate cancers. Prostate Cancer Canada, the Movember Foundation, OICR and The Princess Margaret Cancer Foundation came together to fund the study.

Lalonde began working in Boutros’ lab a few years ago and says that working in the CPC-GENE has been a great experience for a young researcher. “Being part of the network has given me a chance to work with established researchers from a variety of backgrounds. The diverse makeup of the team has allowed us to tackle the challenges of prostate cancer using the combined strengths of researchers and clinicians. The expertise and experience of my supervisors, Dr. Boutros, a researcher, and Dr. Bristow, a clinician-scientist, really put us in a good position to succeed with this study.”

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“This is the first test of its kind that doesn’t require surgery to decide if additional therapy is required,” says Boutros. “From a patient perspective all that is needed is the standard biopsy that is obtained before treatment even begins. There is currently a real dilemma in identifying the men who would benefit from aggressive treatment and those men who would not – this test will provide much more accurate information and allows for improved treatment decisions.”

Bristow agrees that the test will make a big difference in the clinic. “The potential is enormous for thousands of patients. This is a potential way forward to personalize prostate cancer medicine in a major way – an ability to target treatment to patients based on their cancer‘s genetic fingerprint and the factors that affect the environment around those cancer cells. This joint information should lead to improved treatments that increase cure rates by reducing the chances of the cancer recurring and spreading outside the prostate gland.”

The research team is moving quickly to get the test into clinical use. “We are aiming to complete a follow-up study in the next few months using a different technology to give us further technical validation of the test. After that is complete we hope to work with a partner to complete the necessary clinical trials to eventually get the test into hospital labs,” says Lalonde.

 

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