New assessments may help enhance the selection of males contemplating prostate most cancers surveillance

Researchers at the Sylvester Comprehensive Cancer Center are looking at ways to combine imaging and biomarkers to more accurately predict prostate cancer progression. The study was part of an NCI-funded prospective study of men who monitor their prostate cancer through a management process called active monitoring. The results were recently published in the Journal of Urology.

Some types of prostate cancers grow slowly and are unlikely to have long-term consequences. As a result, many men with prostate cancer are at risk of over-treatment and the associated side effects. As a result, active surveillance has emerged as an increasingly popular option for treating prostate cancer.

Prostate and tissue-based genomic marker MRIs are two of the new technologies developed in recent years to improve decision making and risk prediction for men who are monitoring their cancers for progression. This study, dubbed MRI-Guided Active Selection for the Treatment of Prostate Cancer (Miami MAST), provides clarity on how these new tests can be used to improve the selection and monitoring of men who consider monitoring. "

Sanoj Punnen, M.D., Principal Investigator, Co-Chair of the Genitourinary Site Disease Group on New Years Eve, and Associate Professor of Urology at the University of Miami Miller School of Medicine

A new tool for detection and risk assessment

Dr. Punnen and colleagues started the MAST study in 2014 when prostate MRI emerged as one of the newest tools for detecting prostate cancer and assessing its risk.

"Before the MRI, we didn't have a reliable way to map the prostate to differentiate between benign prostate growth and cancer," said Dr. Punnen.

Typically, men with a high prostate specific antigen (PSA) test will get a prostate biopsy to check for cancer.

"We do the biopsy by taking gland samples in 10 to 12 different areas. If only one or two of these nuclei come back with a low-severity cancer, the patient is likely not to need treatment and we are monitoring the cancer," Punnen said .

One of the big problems with active surveillance is that while most patients can handle the surveillance well, the results of the first biopsy underestimate the patient's risk of cancer progression in a small percentage of patients. As a result, many providers perform a prostate biopsy every year to assess progression.

"This can be a nuisance for the patient," said Dr. Punnen. "In the MAST study, the National Cancer Institute (NCI) paid a biopsy and MRI every year for every patient in the study for the first three years. Overall, from a man's diagnosis to his discharge. In this study, we are about five years Data on each patient, "said Dr. Punnen. "Within that time, we have serial MRI imaging of the prostate, 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 the intensity of each one Prostate can be more customized surveillance program for personalized risk of cancer progression. "

While MRI is playing an increasing role in detecting prostate cancer, its role in active monitoring is less clear. In addition, MRI is subjective and can miss between 10% and 30% of clinically significant cancers.

Genomic signatures help predict

Genetic information from biopsy tissue and blood and urine samples add another level of risk stratification to aid decision-making. Sylvester researchers have explored the value of adding genetic data that focuses on genes or signatures that could suggest a risk for more aggressive cancer.

"Many scientists have suggested that these genomic signatures could be more predictive than cancer grade in predicting how aggressive the cancer will be," said Dr. Punnen. "Part of our work in the MAST study was to work with one of the largest genome providers in the field to analyze the genomics of prostate cancer biopsy tissue from men in the study."

One of the problems with genomic testing is that the test is only performed on a single nucleus with the highest grade of cancer. However, prostate cancer is multifocal and heterogeneous, and the nucleus with the highest grade may not always represent the nucleus with the highest genomic risk. Dr. Punnen and his team combined data from the MAST study and another prostate cancer study in radiation oncology (BlaStM study) and reported that the cancer with the highest grade has the highest genomic risk in more than 80% of cases. However, in nearly 20% of cases, the worst genomic risk was found in lower-grade cancer that would not have been analyzed according to standard of care.

"This is a novel finding that provides important information about the pros and cons of these tests in the biopsy setting," said Dr. Punnen.

The article also found that biopsy cores performed with MRI targeting had a higher genomic risk than biopsy cores performed without MRI targeting.

"We believe the Journal accepted our work because it delivers something new about how we can use these signatures and what to look out for," said Dr. Punnen. "At this point we know that using MRI will improve patient monitoring, but now we have all these different data points at the genomic and molecular level for men who are monitoring their tumors to see any changes."

The combination of data points is an advancement in precision medicine that could ultimately improve prostate cancer risk stratification in all men considering prostate cancer surveillance. Dr. Punnen and colleagues recently received a five-year NCI grant of $ 2.9 million to investigate how an artificial intelligence algorithm applied to prostate MRI can further improve prostate cancer risk assessments.

Source:

University of Miami Health System, Miller School of Medicine

Journal reference:

Punnen, S. et al. (2020) Heterogeneity in the Assessment of Genomic Risk Using Tissue-Based Predictive Signatures Used in Biopsy and the Impact of MRI-Targeted Biopsy. Journal of Urology. doi.org/10.1097/JU.0000000000001559.

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