Can early prostate cancer screening help address mortality disparities among Black men?

Among Black men in the United States, as for the overall male population, prostate cancer is the most common noncutaneous cancer and the second-leading cause of cancer mortality. Compared with the whole population, however, prostate cancer among Black men accounts for a higher proportion of both diagnoses (37% vs 29%) and deaths (17% vs 11%) (1,2). In the era of prostate-specific antigen (PSA)–based screening, mortality rates fell at a similar pace among Black and White men, but the excess burden of mortality borne by Black men has not fallen; rate ratios for lethal disease have varied between 2 and 3 over the past 40 years (as high as 4 for younger Black men), the second highest among all major cancers (1,3,4). In fact, in recent years, mortality has risen among Black men—and at a rapid velocity (1). The essential questions that follow are why this disparity persists and what we can do about it. In this issue of the Journal, Kensler et al. (5) present a thorough review of the evidence regarding prostate cancer screening among Black men and make a set of policy recommendations. The review is quite timely, coming close on the heels of the updated (and much-improved) screening guideline from the American Urological Association and Society of Urologic Oncology (6), and should be read in the context of our evolving understanding of both prostate cancer disparities and optimized screening.

Whether Black men should be screened differently depends in part on where the disparity originates on the continuum of tumorigenesis, screening, diagnosis, initial treatment, and subsequent treatment. Kensler et al. (5) review these factors briefly at the start of the article, citing germline genetics and structural racism in terms of access to and quality of care. In terms of the latter, most studies of prostate cancer outcomes after diagnosis have found that with granular adjustment for clinical factors, race is not an independent predictor in multivariable models (7). Rates of definitive therapy are slightly lower for Black than for White men in some studies (8,9) but not others (10). How much these differences represent more undertreatment or less overtreatment among Black men is unclear, but either way, although potentially concerning, they likely explain at most a small proportion of the observed disparity. In terms of screening access, screening before age 60 is actually more common among Black than White men and screening over age 70 less common—although fewer than 25% of Black men undergo testing before age 50 (compared with 15% of White men) (11).

The origins of the mortality disparity, then, seem likely to lie in large part proximal to screening and diagnosis. A genetic contribution is clear; nations in sub-Saharan Africa and the Caribbean face the highest age-standardized rates of prostate cancer mortality in the world, exceeding by as much as an order of magnitude other regions with similar economic development indices (12). Environmental factors unrelated to health care per se play a key role as well; many of these, such as access to healthy diet and exercise, rates of smoking, exposure to environmental toxins, and chronic allostatic stress, reflect chronic structural inequalities (13). Health-care professionals, whether in primary or specialty care, have limited capacity (not to say none) to address these root problems. Therefore, by far the greatest opportunity we plausibly have to improve mortality disparities in the reasonably near-term future is to substantially increase rates of screening among Black men.

To address this possibility, Kensler et al. (5) pose 5 questions: 1) whether Black men should be screened, 2) when screening should start, 3) how often screening should occur, 4) when screening should stop, and 5) which modalities should be used. One critical additional question that should supersede all of these is: What is the purpose of screening? The end goal is reduction of prostate cancer mortality and disease-related morbidity, but any contemporary approach to screening—and certainly any shared decision making conversation—must explicitly acknowledge that the immediate endpoint of interest is identification not of prostate cancer but of potentially lethal disease.

In terms of these specific questions, no serious argument remains that screening reduces prostate cancer mortality, nor is there any reason to suspect that Black men would not benefit at least as much if not more from screening efforts as White men. There is an important flaw in Kensler et al.’s first conclusion, however, that Black men “who elect to undergo screening for [prostate cancer] should be offered a PSA [test].” This statement implies that the onus to initiate shared decision making lies with the patient, not the primary care clinician, which is not appropriate. Indeed, men with sufficient health education and awareness to ask for a test are less likely to have high-grade disease (14). Black men should be offered PSA testing in the context of shared decision making, period—as should all men in good health with a long life expectancy.

When first to offer testing is a crucial question. The United States Preventive Services Task Force (USPSTF) guideline is the only one remaining—though still by far the most influential—to recommend starting at age 55 (15). This age was selected not based on any evidence that it is optimal but rather on the unfortunate methodological decision to consider only the European Randomized Study of Screening for Prostate Cancer and not the Göteborg trial, which started enrollment at 50 years of age (16). Other guidelines—most notably, the new one from the American Urological Association/Society of Urologic Oncology—approach the literature more comprehensively and endorse early baseline testing, reflecting multiple large cohort studies demonstrating the exceptional value of an early baseline PSA measure. Detailed modeling studies, reviewed by Kensler et al. (5), have indicated that regardless of the relative contributions of genetic and environmental factors, prostate cancer has a similar average trajectory in Black and White men but develops about 5 years earlier among Black men, supporting the argument for starting at 40 or 45 years of age among Black men (17). The good news is that—again, as Kensler et al. review—baseline PSA levels overall are similar across racial groups, and low baseline PSA measurements are highly protective in terms of long-term risk, regardless of race. A PSA value under 1.0 ng/mL for a man in his 40s or early 50s can rule out risk of lethal aggressive disease over the next 10 to 25 years—for up to 75% of the population tested (18,19).

The questions of how frequently to test and when to stop are of lesser importance; the policy objective really should focus on any early testing in a higher proportion of Black men. Kensler et al. (5) rightly conclude that evidence regarding intervals and cessation timing for Black men is weak; after all, the parallel evidence is not much better for White men. They note appropriately that screening decisions after the initial baseline should be guided by the baseline level. A man with a PSA level of 0.6 ng/mL at 50 years of age can defer retesting for years; one with a PSA level of 1.4 ng/mL at the same age needs close follow-up if not early workup. Kensler et al.’s guarded recommendation that the utility of testing falls after age 70 (5) should likewise be tempered and individualized: A man with average comorbidity and low PSA levels in the past could likely stop around age 70; conversely, a man in excellent health at 72 years of age who has never had a PSA measurement should be offered one.

Kensler et al. (5) note that the guidelines all advocate primary screening with PSA testing and not digital rectal exam—although if the PSA level is elevated, then the exam becomes an important part of workup rather than screening. An imperative component of early baseline testing with low thresholds for workup is liberal use of secondary tests between PSA testing and biopsy to reduce both unnecessary biopsies and overdiagnosis of low-grade disease. As Kensler et al. discuss, access to magnetic resonance imaging and to blood-based and urine-based biomarker testing is not equitable in current US practice, and this problem must be corrected urgently. The authors note further that most of the available blood and urine tests have not been validated in Black cohorts (5). Two of the listed urine tests (MyProstateScore and ExoDx Intelliscore) are based in part on measurement of ERG fusion RNA transcripts, which are only half as common among Black men as among White men (20); validation of these tests among Black men is particularly necessary.

Kensler et al. (5) conclude that “there is limited evidence to guide [prostate cancer] screening” among Black men and call for additional research to inform recommendations. An alternative argument might be made that we have plenty of evidence today to optimize screening, focusing on 1) early baseline testing (starting at 40 or 45 years of age), with low PSA thresholds (as low as 1.0 ng/mL) for workup; 2) broad use of secondary tests for men with elevated PSA levels to minimize overdiagnosis; and 3) near-universal use of active surveillance for those diagnosed inadvertently with low-grade disease to minimize overtreatment. Major guidelines, with the exception of the USPSTF, now endorse some version of this pathway. Whether the USPSTF will be better aligned with its next revision remains to be seen, but surely increased screening among Black men, particularly at younger ages, would do more than any other near-term achievable intervention to improve prostate cancer health equity and outcomes nationwide.

Data availability

No new data were generated or analyzed for this editorial.

Author contributions

Matthew R. Cooperberg, MD, MPH (Writing—original draft; Writing—review & editing)

Funding

No funding was used for this editorial.

Conflicts of interest

Matthew Cooperberg, a JNCI associate editor and author of this editorial, was not involved in the editorial review of the manuscript or decision to publish the editorial.

Acknowledgements

None.