The Road Ahead for Prostate Cancer Disparity

The year 2020 will be remembered for many reasons, few of them good. But among the fires, floods, locusts, and other natural disasters, two tsunamis have swept the country and the world, unequaled in a generation. The first, of course, is the COVID-19 pandemic; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19), the other is a groundswell of support for racial justice unequaled in breadth and impact since the civil rights movement over a half-century ago. Both have been met with breathtaking indifference and incompetence by a federal government whose three branches have been rendered virtually powerless by the small-minded machinations of a reactionary minority.

What can urologists do? We are a small specialty with relatively little to offer in terms of the pandemic, interesting biologic observations about TMPRSS2 and SARS-CoV-2 notwithstanding. We can join marches and issue departmental statements and participate in what are generally the echo chambers of social media—all important in their own ways but ultimately not much more impactful than any other individuals’ efforts.

One goal we can set—in a lane we swim better than anyone else—is to eliminate, finally, the racial disparity in prostate cancer. Prostate cancer remains by far the most common visceral cancer among men in the United States (US), and the excess burden of disease among African American men is the highest for prostate cancer among all common cancers. African American men, like all US men, have benefited from a sharp drop in mortality rates in the era of prostate-specific antigen (PSA)-based early detection, but continue to face more than twice the mortality rate among Caucasian men. The gap nationwide has narrowed in the past few years, but only slightly.¹ In some regions, great progress has been made; in others, the disparity is worse than ever.²

This is not news; the racial disparity in prostate cancer incidence and mortality has been recognized for decades. For all this time, however, what explains the disparity remains remarkably poorly understood. Potential explanatory factors include innate biological differences, with most of the focus on germline genetic variance; environmental factors, a broad category including dietary and other lifestyle variables, differential exposure to toxins and pollutants, chronic allostatic stressors, and many others; and structural factors, including insurance coverage, logistic access to and quality of care, and neighborhood disadvantage inequalities. While much research has been done, studies nearly always focus on one or a few of these factors; these reductionist viewpoints do identify various differences, but obscure the likely truth that the origins of the disparity are multifactorial and complex, likely reflecting combina­tions of—and interactions among—all three categories of variables.

What does seem increasingly clear is that prostate cancer is not fundamentally different, biologically, between African American and Caucasian men. Comparative genomic studies have identified some germline and somatic differences by race, but at this stage, these are largely descriptive and best considered hypothesis-generating. Given the truism that race in the US is more a social construct than a biological one, this may not be surprising. While some studies have found race to be an independent predictor of prostate cancer outcomes, most—including the largest, multi-cohort analyses—have found that with adequate adjustment for stage, grade, and other clinical parameters, African American men do not have worse cancer outcomes.³ Likewise, large studies of treatment patterns, with adequate adjustment for potential confounders, do not find major differences by race in treatment.⁴

A significant piece of the puzzle, then, may lie prior to diagnosis and primary treatment. Men of African ancestry were essentially non-represented in the European Randomized Study of Screening for Prostate Cancer (ERSPC) screening trial, but detailed analyses of observed screening and incidence data suggest that much of the observed disparity in prostate cancer incidence would be explained by a roughly five-year earlier onset of disease.⁵ The observation that younger African American men bear the highest excess burden of advanced disease (three- to four-fold compared to Caucasian men)⁶ is consistent with this hypothesis.

What combination of genetic, environmental, or structural factors explains this observa­tion is not clear—but the models do suggest that an intervention worth considering at this moment is more aggressive screening among younger African American men. This strategy is reflected in the American Cancer Society and National Comprehensive Cancer Network guidelines, but while screening rates are actually slightly better for younger African American men compared to Caucasian men, they remain far too low.⁷ Median and ranges of PSA levels by age do not vary by race,⁸ supporting the case for early baseline testing among younger African American men, with low thresholds for further workup, extended intervals to subsequent testing for those (the majority) with low initial tests, and high-quality treatment only for those found to have clinically significant, potentially lethal disease.

So as 2020 approaches its end (like the kidney stone of a year it has been—it too shall pass), what can we do? We can take seriously, finally, the goal of eliminating the intractable excess burden of lethal prostate cancer borne by African American men in the US. In the long term, this will require more multidisciplinary, almost certainly multi-center, studies—expensive and difficult, but essential—comparing both biological and environmental factors between African American and Caucasian men. Moreover, all research efforts, even if not focused explicitly on disparities, must accrue more representative populations of men. In the short term, let’s engage with colleagues in primary care and with community and patient organizations to improve both awareness and quality of screening efforts, and redouble our efforts to reach younger African American men.

Written by: Matthew R. Cooperberg, MD, MPH, Professor of Urology, Epidemiology & Biostatistics, Helen Diller Family Chair in Urology, UCSF Department of Urology, University of California, San Francisco, California

References:

1. DeSantis, Carol E., Kimberly D. Miller, Ann Goding Sauer, Ahmedin Jemal, and Rebecca L. Siegel. "Cancer statistics for African Americans, 2019." CA: a cancer journal for clinicians 69, no. 3 (2019): 211-233.
2. Benjamins, Maureen R., Bijou R. Hunt, Sarah M. Raleigh, Jana L. Hirschtick, and Michelle M. Hughes. "Racial disparities in prostate cancer mortality in the 50 largest US cities." Cancer epidemiology 44 (2016): 125-131.
3. Dess, Robert T., Holly E. Hartman, Brandon A. Mahal, Payal D. Soni, William C. Jackson, Matthew R. Cooperberg, Christopher L. Amling et al. "Association of black race with prostate cancer–specific and other-cause mortality." JAMA oncology 5, no. 7 (2019): 975-983.
4. Washington SL 3rd, Jeong CW, Lonergan PE, et al. "Active surveillance for prostate cancer in the United States: trends, predictors, and regional variation." JAMA Netw Open, in press.
5. Tsodikov, Alex, Roman Gulati, Tiago M. de Carvalho, Eveline AM Heijnsdijk, Rachel A. Hunter‐Merrill, Angela B. Mariotto, Harry J. de Koning, and Ruth Etzioni. "Is prostate cancer different in black men? Answers from 3 natural history models." Cancer 123, no. 12 (2017): 2312-2319.
6. Kelly, Scott P., Philip S. Rosenberg, William F. Anderson, Gabriella Andreotti, Naji Younes, Sean D. Cleary, and Michael B. Cook. "Trends in the incidence of fatal prostate cancer in the United States by race." European urology 71, no. 2 (2017): 195-201.
7. Sammon, Jesse D., Deepansh Dalela, Firas Abdollah, Toni K. Choueiri, Paul K. Han, Moritz Hansen, Paul L. Nguyen, Akshay Sood, Mani Menon, and Quoc-Dien Trinh. "Determinants of prostate specific antigen screening among black men in the United States in the contemporary era." The Journal of urology 195, no. 4 Part 1 (2016): 913-918.
8. Preston, Mark A., Travis Gerke, Sigrid V. Carlsson, Lisa Signorello, Daniel D. Sjoberg, Sarah C. Markt, Adam S. Kibel et al. "Baseline prostate-specific antigen level in midlife and aggressive prostate cancer in black men." European urology 75, no. 3 (2019): 399-407.

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