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New Test Developed to Detect Men at High Risk of Prostate Cancer Recurrence

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Key Points

  • Researchers used array comparative genomic hybridization to develop a genetic signature that identified men at high and low risk of their prostate cancer recurring.
  • The test became even more accurate when the genetic signature was combined with additional information about the tumor’s oxygen content.
  • Men with low levels of genetic changes and low hypoxia had the best outcome, with 93% surviving for 5 years without their cancer recurring.

A new genetic signature to identify prostate cancer patients who are at high risk of their cancer recurring after surgery or radiotherapy has been developed by researchers in Canada, according to a study presented at the 33rd Conference of the European Society for Radiotherapy and Oncology in Vienna.

Although surgery and precision radiotherapy are the mainstays of treatment for localized prostate cancer, the cancer will return in 30% to 50% of patients due to metastasis that was undetected during the initial treatment.

Patients in whom treatment has failed within 2 years may be at the highest risk of dying from their prostate cancer, noted Robert Bristow, MD, PhD, FRCPC, of the Princess Margaret Cancer Centre and the University of Toronto.

“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,” he said. “These men can then be offered additional treatments, such as chemo- and hormone therapy, that will combat the prostate cancer throughout their entire body, rather than therapies solely focused on the prostate, in order to improve their chances of survival.”

New Test to Predict Treatment Failure

Dr. Bristow and Paul Boutros, PhD, from the Ontario Institute of Cancer Research, together with their research team, 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. The tumor’s genetic characteristics and its microenvironment were analyzed from biopsy tissue taken before the start of treatment.

“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,” Dr. Bristow said.

The researchers need to validate the test over the next 2 to 3 years in different and larger groups of patients to ensure that it will work successfully in hospitals worldwide. “If all goes well, then this will lead to a new test for cancer patients that can be turned around in 3 days and will tell doctors which patients will do well with local treatment alone—surgery or radiotherapy—and which will need extra treatment,” he said.

Genetic Signature

The researchers analyzed DNA from biopsied tissue taken from 126 men who were predicted to be at intermediate risk of their cancer returning. The men were treated with image-guided radiotherapy, which focuses the radiation more precisely on the tumor, and were followed up for an average of 7.8 years. The researchers used array comparative genomic hybridization to develop the genetic signature that identified men at high and low risk of their cancer recurring.

Then the researchers tested the genetic signature on a second group of 150 patients who were also at intermediate risk of cancer recurrence and who went on to have their tumors removed by radical prostatectomy. The signature test produced results similar to those in the first group.  

Impact of Hypoxia

In a secondary study, the researchers tested the oxygen content of the tumors from men treated with image-guided radiotherapy and found that this also predicted outcome, independently of the genetic signature test. Tumors with high levels of hypoxia were associated with worse survival.

“Importantly, we found that when we combined the signature with the additional information about the tumor’s oxygen content, this made the genetic test even more accurate,” Dr. Bristow said.

Men with low levels of genetic changes and low hypoxia had the best outcome, with 93% surviving for 5 years without their cancer recurring. Men with high levels of genetic alterations and high hypoxia had worse outcomes, with 49% surviving for 5 years without recurrence.

“These results will enable us to develop a new way of personalizing medicine, so that we can improve cure rates and reduce the chances of the cancer spreading to other parts of the body,” concluded Dr. Bristow.

Vincenzo Valentini, MD, President of ESTRO and a radiation oncologist at the Policlinico Universitario A. Gemelli, Rome, Italy, commented, “This is exciting research because an accurate and quick test that can predict which men are most likely to need extra treatment to reduce the risk of a recurrence of their cancer is urgently needed. If the utility of this genetic signature is confirmed in further research over the next few years, it could become an important tool for helping us to better target appropriate treatment according to the genetic make-up of each man’s tumor.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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