Prostate cancer, which usually occurs in older men, forms in tissues of the gland in the male reproductive system found below the bladder and in front of the rectum. Now, a team of Canadian researchers have developed a new genetic signature to identify those prostate cancer patients who are at a high risk of their cancer recurring following surgery or radiotherapy. Dr. Robert Bristow, a professor at the University of Toronto, presented the new research at the 33rd conference of the European Society for Radiotherapy and Oncology in Vienna.

Worldwide, more than 1.1 million cases of prostate cancer were recorded in 2012, and this accounted for nearly eight percent of all new cancer cases. For anywhere between 30 and 50 percent of patients, prostate cancer removed by surgery or radiation will eventually return having spread beyond the reproductive gland. "Existing methods for identifying high risk patients are imperfect, so new tests are required that are better at predicting which patients will have their cancer recur,” said Bristow in a statement.

To identify patients likely to re-experience cancer, Bristow, along with Dr. Paul Boutros from the Ontario Institute of Cancer Research, and a team of researchers, have developed a "signature" based on the DNA of the patient's prostate cancer that can accurately predict treatment failure in patients undergoing radiotherapy or surgery. Analyzing biopsy tissue taken before the start of treatment, the researchers were able to identify genetic characteristics of the tumor and of its microenvironment. To accomplish this, the researchers used a process called array comparative genomic hybridization (aCGH) for analyzing the tumor DNA. This tool helps researchers compare the tumor DNA to a patient’s whole genome in search of areas where there are missing, extra, or irregular sections of DNA.

The researchers first examined DNA from biopsied tissue taken from 126 men. Next, these men were treated with image-guided radiotherapy (IGRT), which focuses the radiation more precisely on the tumor. Then, the researchers followed the group, on average, for close to eight years.  By way of comparison, the researchers tested the genetic signature on a second group of 150 patients who had had their tumors removed by surgery in a procedure known as radical prostatectomy. From all the information they derived, the researchers developed a genetic signature to identify those men at high risk of their cancer recurring.

In a secondary study, the researchers tested the oxygen content of the tumors from men treated with IGRT and found that this also predicted each man’s eventual outcome; tumors with high levels of hypoxia (oxygen deprivation) were linked to those men with the worst survival rates.

Men with low levels of genetic changes and low hypoxia had the best outcome, with 93 percent surviving for five years without their cancer recurring. Men with high levels of genetic alterations and high hypoxia had worse outcomes, with slightly less than half (49 percent) surviving for five years without recurrence. "This is the first report of a test using this information derived from biopsy samples that can predict with close to 80% accuracy which men are at high or low risk of their prostate cancer recurring," Bristow said.

Over the next two to three years, the researchers will work to validate the test in different and larger groups of patients. "If all goes well, then this will lead to a new test for cancer patients that can be turned around in three days and will tell doctors which patients will do well with local treatment alone — surgery or radiotherapy — and which will need extra treatment."

 

Source: Bristow R, Lalonde E, Milosevic M, et al. Complementarity of genomic instability & hypoxia indices for predicting prostate cancer recurrence. European Society for Radiotherapy and Oncology Conference. 2014.