Prostate cancer researchers develop personalized genetic test to accurately predict recurrence risk
U of T researchers have developed a genetic test to identify which men are at highest risk for their prostate cancer to come back after localized treatment with surgery or radiotherapy.
“The clinical potential is enormous for thousands of patients,” said Professor Robert Bristow. “This is personalized cancer medicine to the hilt – the ability to provide more targeted treatment to patients based on their unique cancer genetic fingerprint plus what’s going on in the cancer cell’s surrounding environment.”
The findings are published online in Lancet Oncology. Professor Bristow of the departments of radiation oncology and medical biophysics, and Assistant Professor Paul Boutros, of medical biophysics, report that the gene test provides a much-needed, quick and accurate tool to determine with greater precision the men who will do well with local treatment only (surgery or radiation), and those who will need extra treatment (chemotherapy and hormone therapy) to ensure the cancer is completely eradicated.
“Our findings set the stage to tackle the ongoing clinical problem of under-treating men with aggressive disease that will recur in 30 per cent to 50 per cent of patients due to hidden, microscopic disease that is already outside the prostate gland during initial treatment,” said Bristow, a clinician-scientist at Princess Margaret Cancer Centre.
“This genetic test could increase cure rates in intermediate- to high-risk men by preventing progression to this metastatic spread of prostate cancer.”
The next step will be testing the gene signature on patients worldwide for three to five years to turn the test into one that is readily available in the clinic to guide personalized prostate cancer treatments.
The predictive test analyzes biopsy tissue taken before treatment even starts to identify abnormal genetic characteristics (abnormal DNA) of the prostate cancer and its oxygen content. Low oxygen, or hypoxia, is an already known factor in the spread of prostate cancer. Together, this information can predict with almost 80 per cent accuracy – and in about three days – those prostate cancer patients who are at greatest risk of their disease returning, the study shows.
“We hope to improve cure rates by reducing the chances of the cancer recurring and prevent the cells from spreading,” Bristow said.
The researchers developed the genetic test with two groups of patients. In the first group, the team analyzed DNA from initial diagnostic biopsies of 126 men who were treated with image-guided radiotherapy (IGRT) and followed for an average 7.8 years. In the second group, the team used the test on 150 men whose tumours were removed surgically (radical prostatectomy). The genetic test produced similar results in both groups and therefore can be used in patients who choose radiotherapy or surgery as their initial treatment.
The researchers further found that when testing tumours for hypoxia in the men treated with IGRT and the gene test, this combined information made the test even more accurate, said Dr. Bristow.
The study showed that the men with the best outcomes – lower than 7 per cent recurrence of prostate cancer at five years – had low levels of genetic changes and low hypoxia. For men with high levels of genetic changes and high hypoxia, outcomes were worse – more than 50 per cent of patients had recurrence and these are men who, in the future, could be offered intensified treatment as part of a personalized treatment plan.
Drs. Bristow and Boutros also co-lead the Canadian Prostate Cancer Genome Network (CPC-GENE) Sequencing Project.
Funding was provided by Prostate Cancer Canada, the Movember Foundation, the Ontario Institute for Cancer Research, and The Princess Margaret Cancer Foundation. The study was conducted with assistance from the Wellcome Trust Clinical Research Facility, Addenbrooke’s Clinical Research Centre, Cambridge, U.K.