Genetic Data, Medical Imaging Inform Prostate Cancer Risk Prediction

January 18, 2021 - The use of both genetic data and medical imaging could increase the accuracy of prostate cancer risk prediction, leading to more informed decision-making and proactive care, according to a study published in the Journal of Urology.

Some prostate cancers grow slowly and are unlikely to result in any long-term consequence, researchers noted. This means that many men are at risk for overtreatment and associated side effects, resulting in the emergence of active surveillance as a viable option for prostate cancer management.

“MRI of the prostate and tissue-based genomic markers are two of the new technologies that have emerged over the past few years to improve decision making and risk prediction for men who are watching their cancers for progression,” said principal investigator Sanoj Punnen, MD, co-chair of the Genitourinary Site Disease Group at Sylvester and associate professor of urology at the University of Miami Miller School of Medicine.

“This trial, called the MRI-guided Active Selection for Treatment of Prostate Cancer [Miami MAST] trial, adds clarity to how these new tests might be used to improve the selection and monitoring of men considering surveillance.”

Researchers noted that men typically get a prostate biopsy to check for cancer if they have a high prostate specific antigen (PSA) test.

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“We do the biopsy by taking samples of the gland in 10 to 12 different areas. If only one or two of those cores come back with a low-grade cancer, then the patient likely does not yet need treatment and we monitor the cancer,” Punnen said.

While most patients do well with surveillance, initial biopsy results underestimate patients’ risk for cancer progression in a small percentage of patients. As a result, many providers will conduct a prostate biopsy every year to check for progression.

“That can be burdensome for the patient. In the MAST study, the National Cancer Institute (NCI) grant paid for each patient in the trial to get a biopsy and MRI every year for the first three years. Overall, from the time a man is diagnosed to the time he comes off this trial, we have about five years of data on each patient,” Punnen said.

“Within this time, we have serial imaging of the prostate on MRI, pathology data from serial biopsy, and molecular information from serial blood and urine tests that we can relate to the risk of tumor progression to learn how to better tailor the intensity of each surveillance program to the individual’s personalized risk of cancer progression.”

Although MRI has played an increasingly bigger role in detecting prostate cancer, the technology is subjective and can miss anywhere from ten to 30 percent of clinically significant cancers.

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Using genetic information from biopsy tissue, as well as blood and urine samples, researchers can add another layer of risk stratification to inform prostate cancer decision-making. The team assessed the value of adding genetic data focused on genes or signatures that may indicate risk for more aggressive cancer.

“Many scientists have suggested these genomic signatures may be more predictive than cancer grade in predicting how aggressive the cancer will be,” Punnen said.

“Part of our work in the MAST study has been collaborating with one of the biggest genomic vendors in this space to analyze the genomics from prostate cancer biopsy tissue from men on the trial.”

A chief concern with genomic testing is that these tests are conducted only on a single core with the highest-grade cancer. However, the team stated that prostate cancer multi-focal and heterogeneous, and the core with the highest grade may not always represent the core with the highest genomic risk.

The group combined data from the MAST trial and another prostate cancer trial in radiation oncology and found that the cancer with the highest grade tends to have the highest genomic risk in more than 80 percent of the cases. However, nearly 20 percent of cases found the worst genomic risk in cancer of a lower grade that would not have been analyzed per standard of care.

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“This is a novel finding that adds important information regarding the benefits and limitations of these tests in the biopsy setting,” Punnen said.

The researchers also found that biopsy cores performed with MRI targeting had higher genomic risks than biopsy cores performed without MRI targeting.

The team expects that this combination of genetic and imaging data could evolve precision medicine and advance prostate cancer risk stratification in all men considering prostate cancer surveillance.

“We believe the Journal accepted our work because it provides something new about how we can use these signatures and what we need to be aware of,” Punnen said.

“At this point, we know using the MRI is going to enhance patient surveillance, but now we have all these different data points at the genomic and molecular level on men that are monitoring their tumors to detect change.”