DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

The Impact of a Gene Expression Profile on Treatment Choice and Outcome among Minority Men Newly Diagnosed with Prostate Cancer

Posted September 15, 2021

Dr. Peter Gann, University of Illinois, Chicago
Dr. Adam Murphy, Northwestern University

Dr. Peter Gann
Dr. Peter Gann

Men with relatively low-risk prostate cancer (PCa) face a difficult decision between immediately treating the cancer, often by surgery or radiation, or instead choosing active surveillance (AS) to monitor the cancer over time and possibly defer or even avoid treatment if the cancer doesn’t progress. AS is considered a safe alternative for properly selected patients and can reduce potentially unnecessary treatments and their associated side effects. The adoption of AS in the United States has increased dramatically in recent years, although its adoption in Black men, who are at an increased risk for PCa mortality, may be lagging. There are concerns by PCa providers about whether AS is an equally safe alternative to treatment for Black men due to factors that disproportionately affect this group of men, such as increased biologic aggressiveness of the cancer and reduced compliance with treatment follow-up due to healthcare access issues. For patients considering AS, the Oncotype DX Genomic Prostate Score (GPS) test can be performed on biopsy tissue to predict adverse clinical outcomes using expression levels of 12 known PCa genes plus clinical features of the tumor biopsy. This test has shown promise for increasing rates of AS for men with low or intermediate risk PCa, although studies to validate its clinical utility were conducted in mainly White, affluent populations. Dr. Peter Gann (University of Illinois, Chicago), and Dr. Adam Murphy (Northwestern University) teamed up to conduct a randomized clinical trial in a predominantly Black population to determine the effects of adding GPS to standard risk counseling for PCa decision making.

Dr. Adam Murphy
Dr. Adam Murphy

With funding from an FY14 Biomarker Development Award, Drs. Gann and Murphy sought to determine the true clinical utility of the Oncotype DX GPS test and how it impacts actual treatment decisions. Through their ENACT (Engaging Newly Diagnosed Men About Cancer Treatment Options) clinical trial, they recruited 200 men, predominantly representing Black patients, with low risk PCa from three public hospitals in Chicago. These men were randomly assigned at the time of PCa diagnosis to standard risk counseling with or without the GPS test to see how the test would influence their decision to try AS. Through this trial, they found that although a high level of AS adoption was achieved overall (80.7% of Black participants and 73.3% of non-Black participants), more men who had GPS added to the standard risk counseling chose immediate therapy instead. This effect was markedly evident in men with low health literacy (46% of their study population), who were seven times more likely to reject AS if they received GPS compared to men with higher health literacy, even after factors such as the patient’s risk of aggressive cancer (as determined by established clinical factors were taken into consideration). This suggests that the net impact of GPS on treatment choice is very different in this study population than has been previously reported, and that men who struggle to understand their medical diagnosis and treatment options are most likely to reject the long-term commitment of surveillance if they receive the test. These results stress the need for better educational support for low literacy patients so they can better make informed treatment decisions and possibly improve their physical quality of life by deferring unnecessary treatments.

Through the ENACT trial, Drs. Gann and Murphy also established the largest cohort of Black men on AS, with a median follow-up of 1.8 years. They plan to extend the follow-up of this cohort to answer new questions regarding risk of progression and factors affecting adherence to AS in Black men. Recent data has shown that multiparametric MRI (mpMRI) can be a useful tool to help select patients for AS, although this has not been tested in Black patient populations. The team recently received an FY20 Translational Science Award to test the hypothesis that additional risk assessment with mpMRI could increase patient adherence to AS in Black and low income men. Overall, they hope to improve the safety and uptake of AS in these men, and by allowing them to more confidently choose AS and avoid treatment-related morbidity, and increase their overall quality of life.

Gann Murphy Figure

Publication:

Murphy AB, Abern MR, Liu L, Wang H, Hollowell CMP, Sharifi R, Vidal P, Kajdacsy-Balla A, Sekosan M, Ferrer K, Wu S, Gallegos M, King-Lee P, Sharp LK, Ferrans CE, Gann PH. Impact of a Genomic Test on Treatment Decision in a Predominantly African American Population With Favorable-Risk Prostate Cancer: A Randomized Trial. J Clin Oncol. 2021 May 20;39(15):1660-1670. doi: 10.1200/JCO.20.02997. Epub 2021 Apr 9. PMID: 33835822; PMCID: PMC8148420.

Link:

The Impact of a Gene Expression Profile on Treatment Choice and Outcome among Minority Men Newly Diagnosed with Prostate Cancer: A Randomized Trial

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Last updated Wednesday, September 15, 2021