Utilizing a model-based analysis in prostate cancer screening among Black men

From the Etzioni and Nyame Group, Division of Public Health Sciences

For at least five decades, prostate cancer mortality rates among Black men have been two-fold higher than the mortality rates of other races. This is the most severe racial disparity among all cancers in the US. In several studies, a cancer survival disparity did not exist between Black and white men when matched by disease severity settings of equal treatment access. In contrast, Black men are diagnosed at a younger age and with more advanced stages of prostate cancer than white men. In order to decrease the racial disparity within mortality rates, Black men should be screened earlier in life and given definitive therapy to combat clinically significant disease. Prostate-specific antigen (PSA) screening is similar between Black and white men. However, there are varied reports of positive tests from prostate biopsies between Black and white men. Some studies have reported less use of prostate biopsies among Black men. The Etzioni and Nyame Group, from the Division of Public Health Sciences, evaluated the impact of heightening screening in Black men to maximize the early detection of cancers that can be cured with definitive treatment. Dr. Nyame, first author of the study, explained, “Black men are twice as likely to die from prostate cancer as men of all other races/ethnicities in the US and are diagnosed with prostate cancer at younger ages.  Yet current guidelines from the USPSTF do not provide any recommendations for early detection among Black men.  Our study provides evidence that annual PSA screening of Black men between 45-69 years reduces deaths from prostate cancer beyond the benefit observed with historic screening practices.”  The researchers increased PSA testing and prostate biopsy for abnormal test results and considered earlier and later ages for starting and ending testing. By assessing the impact of intense prostate cancer screening in Black men, the researchers’ goal is to work towards achieving racial equity in prostate cancer.  The study is published in the Journal of the National Cancer Institute.

Within a historical context, prostate screening happens biennially for PSA testing in men ages 50-84 years and the biopsy rate is 40% for abnormal PSA testing. In this study, researchers intensified early detection to consist of more PSA testing and/or increased frequency of prostate biopsy in Black men with elevated PSA concentration. The researchers utilized two microsimulation models to investigate the impact of intensified early detection on prostate cancer mortality and overdiagnosis among Black men. Dr. Nyame stated, ““This study leverages models developed through the CISNET collaborative group and allowed us to measure the benefit and harm of various screening strategies in the absence of clinical trial or screening cohort data.  In fact, Black men represent 3% or fewer of participants in the major prostate cancer screening trial worldwide.”  In the Fred Hutchinson Cancer Research Center model, cancer grade remains the same as the progression of cancer is correlated with individual PSA growth trajectories. In the Erasmus Medical Center microsimulation screening analysis model, cancer progresses by stages and grades, but it is not correlated with individual PSA growth trajectories.  The simulated, calibrated models consist of a greater risk of disease and onset of progression among Black men compared to all other races. The simulations represent the population disease experience of onset, progression, and diagnosis. The mean lead time (MLT) is the average time by which screening advances detection under a specific screening strategy. In analyses, the MLT based estimates increase the benefits of prostate cancer screenings. The authors analyzed the following factors for intense early detection by calculating MLT: the impact of increasing the frequency of screening and biopsies on mortality reduction, the effect of increasing the biopsy rate to 100% for men with a positive test, and the consequences of using different start and stop ages for screening. 

Graphical Representation of Fred Hutchinson Cancer Research Model
Fred Hutchinson Cancer Research Model Image from Dr. Nyame
Graphical Representation of Erasmus Medical Center MIcrosimulation Screening ANalysis Model
Erasmus Medical Center MIcrosimulation Screening ANalysis Model Image from Dr. Nyame

In both models, Black men had a higher incidence of latent disease compared to other races. In turn, Black men had more screenings and higher rates of overdiagnosis per 1,000 men. Black men’s MLTs under historical screening and biopsy were 2.8-3.5 years compared to 2.7-2.6 years for other races. Mortality was reduced by an estimated 21-24% among Black men and 20-24% among other races by historical screening and prostate biopsy utilization. However, there were 75-86 overdiagnoses per 1,000 men screened among Black men. When screening was restricted to 55-69 years, there was a mortality reduction of 18-20% and a lowered overdiagnosis rate of 33 per 1,000 men. When biopsy utilization was increased to an upper bound of 100% of positive tests, this yielded the largest mortality reduction (31-35%) and an inflation of overdiagnosis to historical levels of 67-88 per 1,000 men. The intensified early detection strategy using the Fred Hutchinson Cancer Research Center model yielded the following outcomes: 50 prostate cancer deaths with no screening, 40 prostate cancer deaths per 1,000 men with screening at a historical frequency, and 35 prostate cancer deaths for ages 45-69 years with annual screening when prostate biopsy rate was not increased from historical levels.

Currently, limited resources exist on racial disparities and PSA screening for prostate cancer outcomes. The Etzioni and Nyame Group found that racial parity can be developed by increasing the frequency of PSA testing in Black men. Due to high rates of overdiagnosis and preclinical disease in Black men, screening interventions should target men under 70 years old. The authors agreed that a screening strategy that minimizes overdiagnosis – and subsequent treatment - is prudent as we explore ways to use early cancer detection to minimize racial disparities in prostate cancer outcomes. Dr. Nyame elaborated, “The next step of this study is in understanding how we can develop patient centered studies to support and operationalize the screening strategies that showed increased benefit for Black men in our models.”

This research was supported by the Department of Defense and the National Cancer Institute.

Fred Hutch/UW Cancer Consortium members Yaw A Nyame, John L. Gore, and Ruth Etzioni contributed to this work.

Nyame YA, Gulati R, Heijnsdijk EA, Tsodikov A, Mariotto AB, Gore JL, Etzioni R. The Impact of Intensifying Prostate Cancer Screening in Black Men: A Model-Based Analysis. JNCI: Journal of the National Cancer Institute. 2021 May 8. https://doi.org/10.1093/jnci/djab072