Degree of Genomic Damage and Hypoxia Predict Likelihood of Prostate Cancer Relapse

A team of Canadian cancer researchers has developed a test based on genetic and environmental indices that distinguishes between prostate cancer patients with low or high risk of relapse following treatment.

Clinical prognostic groupings for localized prostate cancers are imprecise, with the tumor recurring in 30%–50% of patients following image-guided radiotherapy or radical prostatectomy. Investigators at the Princess Margaret Cancer Center (Toronto, ON, Canada) tested combined genomic and environmental (level of hypoxia) indices in prostate cancer to improve risk stratification and complement clinical prognostic factors in order to differentiate between patients with high or low risk of relapse.

To this end they worked with two groups of patients. DNA was extracted from pretreatment biopsies that consisted of at least 70% tumor cells as estimated by a pathologist, and a custom DNA array was used to detect gene copy number alterations. Intraglandular measurements of partial oxygen pressure were taken before radiotherapy with an ultrasound-guided transrectal needle piezoelectrode.

In the first group of patients, the investigators 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, they applied the test to 150 men whose tumors were removed surgically (radical prostatectomy).

Results revealed that patients with the best outcomes—less than 7% recurrence of prostate cancer at five years—had fewer genetic changes and lower levels of hypoxia. For men with multiple genetic changes and high levels of hypoxia, outcomes were worse—more than 50% of patients had recurrence.

Senior author Dr. Robert Bristow, a clinician-scientist at Princess Margaret Cancer Center, said, "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 many more 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."

"Our findings set the stage to tackle the ongoing clinical problem of under-treating men with aggressive disease that will recur in 30% to 50% of patients due to hidden, microscopic disease that is already outside the prostate gland during initial treatment," said Dr. Bristow. "The clinical potential is enormous for thousands of patients. 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 is going on in the cancer cell's surrounding environment. We hope to improve cure rates by reducing the chances of the cancer recurring and prevent the cells from spreading."

The study was published in the November 12, 2014, online edition of the journal Lancet Oncology.

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Princess Margaret Cancer Center