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Both biologic and socioeconomic factors may be to blame. Better screening may help to close the gap.

INA WU, MD
Glickman Urological and Kidney Institute, Cleveland Clinic

CHARLES S. MODLIN, MD, MBA
Executive Director, Minority Health; Director, Minority Men’s Health Center; Staff, Glickman Urological and Kidney Institute, Cleveland Clinic; Associate Professor of Surgery, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

ADDRESS: Charles S. Modlin, MD, MBA, Glickman Urological and Kidney Institute, Q10-1, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail modlinc@ccf.org

ABSTRACT
African-American men have a higher incidence of prostate cancer than white men, and also a higher rate of death due to prostate cancer. Although both biologic and socioeconomic factors may be to blame, better screening in this population may help to close the gap.

KEY POINTS

  • African American men have the dual disadvantages of being less likely to receive adequate care and also, possibly, of having biological differences that make them more prone to prostate cancer and more aggressive cancer.
  • Prostate-specific antigen (PSA) cutoff levels have not been officially modified according to race, but we believe primary care physicians should have a lower threshold for referring African American men who have a suspiciously high PSA level for further urologic evaluation.
  • A healthy lifestyle, with a low-fat diet, healthy body mass index, and daily exercise, may decrease the risk of prostate cancer, among other benefits.
  • Primary care physicians, who are often the gatekeepers to care, play a key role in educating and screening their patients.
Prostate cancer is the most common cancer affecting American men. In 2010, an estimated 217,730 men were diagnosed with it and 32,050 died of it.1 African American men are disproportionately affected, with a prostate cancer incidence two-thirds higher than whites and a mortality rate twice as high.1 Owing to such disparities, the life expectancy of African Americans is several years shorter than that of non-Hispanic whites.2

For the primary care provider, who is often the first access point for health care in the United States, it is important to understand what mechanisms may underlie these differences and what can be done to narrow the gap.3

WHAT IS THE CAUSE OF THESE DIFFERENCES?

Many studies have looked into the causes of the higher incidence of prostate cancer in African-American men and their higher mortality rate from it. The disparity may be due to a variety of factors, some socioeconomic and some biologic.

Poorer access to care, or lower-quality care?

A study of US servicemen who had equal access to care showed that African American men had a higher rate of prostate cancer regardless of access to care and socioeconomic status.4

However, the 2002 Institute of Medicine report, Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care, found evidence that racial and ethnic minorities tend to receive lower-quality health care than whites, “even when access-related factors, such as patients’ insurance status and income, are controlled.”5

Genetic predisposition?

Some have proposed that the disparity may be a function of genetic predisposition.

Evidence of a genetic component to the high incidence and mortality rate in African American men comes from epidemiologic studies of men with similar genetic backgrounds. For example, men in Nigeria and Ghana also have a high incidence of prostate cancer, as do men of African descent in the Caribbean islands and in the United Kingdom.6

Chromosome 8q24 variants have been shown in several studies to be associated with prostate cancer risk and are more common in African American men.7–10 Some studies have also shown a higher rate of variations in cell apoptosis genes such as BCL211 and tumor-suppression genes such as EphB2 in African American men.12

These findings suggest that genetic differences may contribute to the higher prostate cancer incidence and mortality rate seen in African American men.

More-aggressive cancer, or later detection?

Not only do African American men tend to have a higher incidence of prostate cancer, they also tend to have more aggressive disease (ie, a higher pathologic grade) at the time of diagnosis, which may contribute to the disparity in mortality rates.13–19

Initially, there was some controversy as to whether this observation is a result of genetic and biologic factors that may predispose African American men to more-aggressive disease, or if it is due to inadequate screening and delayed presentation. However, a body of evidence supports the contention that prostate cancer is more aggressive in African American men.

For example, a study of autopsy data from men who died of prostate cancer at ages 20 to 49 showed that the age of onset of prostate cancer was similar between African American and white men.20 The Surveillance Epidemiology and End Results (SEER) database showed that African American men had a higher incidence of metastatic disease across all age groups.20A similar study conducted 10 years later confirmed that rates of subclinical prostate cancer in African American and white men do not differ by race at the early ages, but that advanced or metastatic disease occurred nearly four times as frequently in African American men.21

Another study examined prostate biopsies from African American men and found that their tumors expressed higher levels of biomarkers, suggesting they had more-aggressive disease.22

SCREENING FOR PROSTATE CANCER

Serum prostate-specific antigen (PSA) testing has become the method of choice for prostate cancer screening. However, PSA screening in asymptomatic men is under debate, because it can lead to overdetection and subsequent overtreatment of indolent disease.23

Several recent studies showed differing results from prostate cancer screening.

The US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial found that the mortality rate was no lower with combined PSA screening and digital rectal examination during a median follow-up of 11 years than in a control group that had a lower rate of screening.24 However, further analysis of these data, with stratifying by comorbidities, showed that PSA screening in young and healthy men reduces the risk of death from prostate cancer, with minimal overtreatment.25

The European Randomized Study of Screening for Prostate Cancer found a statistically significant 20% reduction in deaths from prostate cancer with PSA screening, but that it was necessary to treat 48 men in order to save one life.26

Another study, published in 2010, showed that regular PSA screening reduced the rate of prostate cancer mortality by half over 14 years.27

African American men generally present with disease that is more advanced than in white men.28 This historically has been attributed to the fact that African Americans have been less likely to be screened for prostate cancer, though recent data indicate the gap is lessening.29–31 A cross-sectional study from the Texas Medical Center showed that 54.4% of African American men had received PSA screening, compared with 63.2% of white men.32

Another study showed that African Americans were more likely to have had a longer interval between PSA screenings before diagnosis, and that a longer PSA screening interval was associated with greater odds of having advanced disease at diagnosis.33 However, when the researchers controlled for the PSA screening interval, they found that African Americans had the same odds of being diagnosed with advanced prostate cancer as white patients did. They concluded that more frequent or systematic PSA screening may reduce the racial differences in cancer stage at diagnosis and in deaths.

Reasons for the disparities in screening

Many reasons have been proposed to explain why African Americans receive less screening, including poor communication between physicians and minority patients due to lack of cultural competency among physicians, lack of health insurance (and poor access to quality care as a result), and deficiency of knowledge about screening. Though awareness is rising, many African Americans are unaware of early detection methods for prostate cancer (eg, PSA testing), and other barriers such as cost and transportation exist that may prevent African American men from being screened.34,35

As gatekeepers, primary care physicians are in a position to address these shortcomings in patient education and to enhance the physician-patient relationship.36

Black men have higher PSA levels, with or without cancer

Physicians must also be aware of racial differences in PSA levels and realize that the predictive value of PSA in the diagnosis of prostate cancer may differ between African Americans and whites.

Black men, with or without prostate cancer, have been found to have higher PSA levels. Kyle and colleagues37 found that African American men without prostate cancer had significantly higher mean PSA levels than white men across all age groups. Furthermore, Vijayakumar et al38 found that African Americans with newly diagnosed localized prostate cancer had higher serum PSA levels than whites at diagnosis.

Although PSA cutoff levels have not been officially modified according to race, primary care physicians should have a lower threshold for referring African American men who have a suspiciously high PSA level for further urologic evaluation. Close partnership between the internist, family practitioner, and urologist will aid in the optimal use of PSA testing for the early detection of prostate cancer.

When to start PSA screening? How often to screen?

The age at which African American men should begin to have their PSA levels checked (with or without a digital rectal examination) continues to debated. However, the American Cancer Society39 recommends that African American men who have a father or brother who had prostate cancer before age 65 should begin having discussions with their physician on this topic and, with their informed consent, screening at age 45.

The frequency of PSA screening depends on the individual’s PSA level. The National Comprehensive Cancer Network40recommends that men at high risk be offered a baseline PSA measurement and digital rectal examination at age 40 and, if the PSA level is higher than 1 ng/mL, that they be offered annual follow-ups. If the PSA level is less than 1 ng/mL, they recommend screening again at age 45. Risk factors for prostate cancer include family history as well as African American race.41

How should PSA levels be interpreted?

Interpreting PSA results is important in detecting prostate cancer at early stages.

At first, we believed the normal range of PSA for all men was 4.0 ng/mL or less. However, the American Urological Association now recognizes that the normal PSA range, in addition to varying along racial lines, also is age-dependent.42The Cleveland Clinic Minority Men’s Health Center’s suggested normal ranges of PSA in African American men are:

  • Age 40–49: ≤ 2.5 ng/mL
  • Age 50–59: ≤ 3.0 ng/mL
  • Age 60–69: ≤ 3.5 ng/mL
  • Age 70–79: ≤ 4.5 ng/mL
  • Age > 80: ≤ 5.0 ng/mL.

Remember that an elevated PSA does not necessarily signify prostate cancer, and that these are reference ranges only and may vary in individual men.

SURVIVAL AFTER DIAGNOSIS

African American men with prostate cancer have significantly higher mortality rates than white men. The possible causes of worse outcomes are many, and there have been many studies that attempted to address this disparity. The question of a more biologically aggressive cancer was previously discussed, but additional factors such as socioeconomic factors, comorbidities, and treatment received have also been studied, and data are mixed.43–45

In a large SEER database review, once confounding variables of socioeconomic status, cancer stage, and treatment received were eliminated, African Americans had similar stage-for-stage survival from prostate cancer.46 Another study found, in 2,046 men, that differences in socioeconomic status explained the difference in mortality rates between white and black patients.47

However, other studies that adjusted for socioeconomic status as well as patient and tumor characteristics found that African American and Hispanic men were more likely to die of prostate cancer than white men.48

Do African American men receive less-aggressive care?

Studies have also determined that there may be differences in treatments offered to patients, which in turn negatively affect survival.28,49–53 Potentially curative local therapies (including radical surgery or radiation) may be recommended less often to black men because of major comorbidities or socioeconomic considerations.49–52

Additionally, potential metastatic disease may be identified in a less timely and accurate manner, as African-American men are less likely to undergo pelvic lymph node dissection. This was associated with worse survival in men with poorly differentiated prostate cancer.53

However, returning to the possibility that prostate cancer is biologically more aggressive in African American men, some studies have shown that even after adjusting for treatment, African Americans continue to have worse survival rates.54,55One study in men with stage T1 to T3 prostate cancer who chose brachytherapy for treatment reported that after adjusting for PSA, clinical stage, socioeconomic status, and comorbidities, African American and Hispanic race were associated with higher all-cause mortality rates.55

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