Racial Disparities in Prostate Cancer: Incidence, Mortality, and Treatment Outcomes

Introduction

Prostate cancer represented a significant global health challenge in 2020, with an estimated 1,414,259 new cases reported worldwide. It stands as the second most common cancer among men globally, surpassed only by lung cancer. The impact is further underscored by the estimated 375,304 deaths attributed to the disease in the same year, according to the Global Cancer Observatory [1]. While incidence rates are rising in many parts of the world, including Asia—potentially linked to increased prostate-specific antigen (PSA) screening, dietary westernization, and longer lifespans—stark racial and ethnic differences in prostate cancer incidence and mortality persist. African-American men, for instance, face disproportionately higher rates compared to other groups. Despite the known existence of these disparities, a comprehensive contemporary review is vital for understanding the current landscape. This review synthesizes available evidence on racial differences in prostate cancer characteristics, risk factors, screening considerations, treatment responses, genomic profiles, and overall mortality, highlighting critical areas impacting men’s health. As of April 2022, appreciating the depth and breadth of these disparities remains crucial for developing equitable healthcare strategies and improving outcomes for all men.

Global cancer statistics for 2020 showing estimated deaths and new cases, highlighting prostate cancer's prevalence among men.

Evidence Acquisition

To gather relevant information, a systematic search was conducted across multiple databases including PubMed, MEDLINE, Embase, Web of Science, Scopus, and the Cochrane database. Recent conference abstracts were also reviewed. The search focused on studies published before April 30, 2021, addressing racial differences in prostate cancer. Keywords used included “prostate cancer,” “prostate carcinoma,” “prostatic cancer,” “racial difference,” “human race specificity,” and “ethnic group.” Two independent reviewers (N.H., M.F.) screened the literature, noting reasons for exclusions. Selected studies underwent critical evaluation and full-text review to confirm relevance. Any disagreements between reviewers were resolved through consensus involving all co-authors.

Racial Differences in Incidence and Mortality

Profound variations exist in prostate cancer incidence rates across different global populations, with rates in some countries being 60 to 100 times higher than in others [2]. Generally, Asian men exhibit low incidence rates, with age-adjusted figures ranging from 2 to 10 per 100,000 men. Conversely, Northern European countries tend to report high incidence. African-American men experience the highest incidence rates globally.

World maps illustrating the estimated age-standardized incidence rates (A) and mortality rates (B) of prostate cancer by country in 2020.

Mortality rates also show significant racial disparities (Fig. 2B). In the United States, the incidence among African-American men is approximately 60% higher than among Caucasian men [3], and their prostate cancer-specific mortality rate is more than double that of non-Hispanic Caucasian men [4]. Specifically, African Americans in the USA have incidence and mortality rates roughly twice those of European American men and three to four times higher than Asian Americans [5]. However, there is some evidence suggesting that these race-specific differences in survival estimates might be narrowing over time [6].

Racial Differences and Prostate-Specific Antigen Screening

The disparities faced by African-American men are particularly stark: a 64% higher incidence rate and a 2.3 times higher mortality rate compared to Caucasian men [7, 8]. Autopsy studies suggest that prostate cancer may become more biologically active at a younger age in African-American men [8]. Data also indicate an earlier age of onset. Analysis of 2010 SEER data showed non-Hispanic Caucasian men were diagnosed 1.2 years later on average than non-Hispanic African-American men [9]. An earlier SEER analysis found a 3-year age difference at diagnosis [10]. A UK study reported Caucasian men were diagnosed a mean of 5.1 years later than men of African descent [11], and another estimated men of African descent were twice as likely to be diagnosed before age 45 [12].

These findings have led to proposals for race-specific PSA reference ranges for biopsy decisions [13]. Modeling studies further suggest African-American men might have a higher burden of preclinical disease and increased metastatic risk compared to Caucasian Americans [14]. Baseline PSA levels are considered strong predictors, potentially more so than race itself [15]. A large study within the VA Health Care System found the optimal PSA threshold for predicting cancer diagnosis within 4 years was lower for African-American men (1.9 ng/mL) than for Caucasians (2.5 ng/mL) [16]. Prospective data also indicate that Black men aged 40-64 with PSA levels in the highest decile face a significantly elevated risk of aggressive prostate cancer [17].

Multiple factors contribute to these racial disparities, including genetic predispositions, environmental exposures, differences in patient and physician behaviors, socioeconomic factors affecting access to quality care (including screening and follow-up), delayed diagnosis, and inadequate treatment [18–22]. Additionally, earlier onset of puberty in males has been proposed as a potential risk factor contributing to racial disparities in prostate cancer burden [23].

Given the higher incidence, mortality, younger age at diagnosis, and potential for earlier progression in African-American men, it is reasonable to recommend initiating discussions about PSA screening (shared decision-making) at age 40, potentially considering annual screening rather than biennial screening for this population [14].

Regarding Asian populations, incidence and mortality rates are significantly lower compared to North America, Europe, and Oceania. However, Asian immigrants in Western countries tend to have higher incidence rates than those residing in their birth countries. Lower PSA screening rates in Asian countries and among some Asian immigrant groups may partially explain these lower incidence figures [24].

Racial Differences and Treatment

Race is increasingly recognized as a crucial factor in managing localized prostate cancer, particularly concerning active surveillance candidacy for African-American men. Data from 2010-2012 indicated Black men had higher lifetime risks of both developing prostate cancer (18.2% vs. 13.3%) and dying from it (4.4% vs. 2.4%) compared to Caucasian American men [25]. One study noted that the increased mortality in African-American men was primarily seen in those with grade group 1 disease [26].

Several studies suggest that Black men classified with very low-risk prostate cancer based on biopsy might harbor higher-grade disease (grade group ≥2) that was missed. Pathological upgrading at prostatectomy has been reported to be 1.7 to 2.3 times more common in African-Americans compared to clinically matched Caucasian Americans [27, 28]. However, not all studies concur, with some finding no significant differences in upgrading or staging rates [26, 29, 30].

Among men enrolled in active surveillance programs, some studies report a higher risk of progression (to higher Gleason grade or tumor volume) for African-Americans compared to Caucasian Americans with low-risk disease [31–33]. African-Americans in low- to moderate-risk groups may also face a higher risk of biochemical recurrence following definitive treatment [34]. Furthermore, African-American patients with favorable-risk prostate cancer have shown higher overall post-treatment mortality, potentially linked to cardiovascular complications after androgen deprivation therapy (ADT) [35].

The reasons for these clinical discrepancies are multifaceted. Differences in tumor biology, potentially reflecting distinct prostate cancer subtypes associated with gene expression variations, may play a role [21, 36–38]. Disparities in treatment access and quality of care are also significant contributors [39, 40]. Multi-parametric magnetic resonance imaging (mpMRI) combined with targeted biopsies is emerging as a tool to improve risk stratification, particularly for African-American men considering active surveillance, by enhancing the detection of clinically significant cancers [41].

A large analysis using the National Cancer Database (NCDB) examined survival outcomes. No significant racial disparity in survival was found between African American and Caucasian men presenting with bone metastasis (p=0.885) or other distant metastases (liver, lung, brain). However, a significant survival disparity favoring Caucasian men was observed among those with non-metastatic prostate cancer (p<0.001) [42].

Another NCDB study evaluating 526,690 patients post-radical prostatectomy found that after adjusting only for age and diagnosis year, Black men had 51% higher mortality, while Asian Americans and Pacific Islanders (AAPIs) and Hispanic men had 22% and 6% lower mortality, respectively, compared to Caucasians. After adjusting for clinical and socioeconomic factors (education, income, insurance), the Black-White mortality disparity narrowed to 20%, while the AAPI survival advantage increased (35% lower mortality than Whites). Access-to-care related factors like education, income, and insurance status were major contributors to the observed racial disparities [43].

Regarding radiation therapy, an NCDB analysis of 27,150 men found equivalent overall survival (OS) between Black and Caucasian men in both favorable-risk (HR 0.928, p=0.753) and unfavorable-risk subgroups (HR 1.078, p=0.550) after radiotherapy. While no significant interaction between treatment and race was found overall, a significant interaction between race and age emerged in the unfavorable-risk group (p=0.015), with Caucasian men aged ≤60 years showing better OS (HR 0.320, p=0.009) [44].

For Asian populations, a systematic review indicated that prostate cancer survival rates in Asian countries are generally lower than in Europe and North America. This may be linked to reduced access to diagnostic facilities and potentially older age at diagnosis compared to more developed nations. However, countries with a very high human development index (e.g., South Korea, Japan) showed survival rates comparable to Western countries [45].

Racial Differences in Genomic Profiling of Prostate Cancer

Genomic analyses reveal differences in tumor mutation frequencies across racial groups. A study involving 2,393 men (80 Asian, 2,109 White, 204 Black) examined genomic profiles in primary and metastatic prostate cancer [46].

In primary tumors (n=1,484):

• A higher proportion of Asian men (11.5%) had a high tumor mutational burden (>20 mutations).
• FOXA1 mutations were more frequent in Black men (18.6%) and Asian men (37.8%) compared to White men (11.9%).
• TP53 mutations were less frequent in Black men (14.2%) compared to White men (20.6%).
• Androgen receptor (AR) mutations were rare across all races.
• Frequencies of actionable mutations (targets for precision oncology) and DNA-repair gene mutations did not differ substantially by race.

In metastatic tumors (n=909):

• A proportion of Black men (6.8%) had a high tumor mutational burden.
• AR mutations were more frequent in Black men (18.3%) than White men (8.1%).
• TP53 mutations were more frequent in Asian men (62.0%) compared to both Black (22.5%) and White men (36.4%).
• Actionable mutations were potentially more frequent in Black men (26.7%) than White men (18.0%, p=0.05).
• DNA-repair gene mutations were potentially more frequent in Black men (22.5%) than White men (15.6%, p=0.05).
• BRAF mutations, generally rare in prostate cancer but actionable, were significantly more frequent in Black men (7.0%) compared to White men (1.5%).

These findings suggest that clinically relevant genomic alterations occur at different frequencies across races. Notably, Black men with metastatic disease showed higher rates of mutations in AR, DNA-repair genes, and potentially actionable targets compared to White and Asian men [46].

Germline mutations in genes like BRCA1 and BRCA2 are present in about 0.2-0.3% of the general population, with varying prevalence across ethnic groups [47]. These mutations are linked to increased prostate cancer risk [48–57]. BRCA2 mutations, in particular, confer a 2 to 6-fold increased risk, while the association with BRCA1 is less consistent [49, 51, 52, 57–59]. Prostate cancers developing in men with BRCA germline mutations tend to be more aggressive, occur earlier, and are associated with shorter survival times [60–65]. Importantly, a significant proportion (around 60%) of men with fatal prostate cancer carrying BRCA1/2 or ATM mutations may lack a relevant family history [62].

Other genes linked to prostate cancer risk through family studies include RNASEL, ELAC2, MSR1, and HOXB13 [66]. The HOXB13 G84E mutation confers a substantially higher risk (3.3 to 20.1 times) [66, 67]. This mutation’s prevalence varies geographically and ethnically, being more common in individuals of European descent (especially Northern European) and largely absent in families of African, Jewish, or Chinese origin with familial prostate cancer [68, 69].

Genome-wide association studies (GWAS) have identified nearly 100 single-nucleotide polymorphisms (SNPs) associated with prostate cancer risk, many located in the 8q24 chromosomal region [70–72]. However, the frequencies of these risk alleles differ across racial groups, contributing to the observed disparities in incidence [72, 73].

BRCA Mutation Carriers and Treatment Considerations

Men carrying BRCA mutations face a higher risk of developing prostate cancer compared to the general population, although prevalence varies significantly by race [74, 75]. Prostate cancer exhibits strong familial clustering: having one first-degree relative with the disease doubles the risk, while having two or more increases the risk 5- to 11-fold [76]. For BRCA mutation carriers, the risk is further elevated – approximately 2-fold for BRCA1 and 5- to 7-fold for BRCA2 carriers [77].

The management approach for BRCA mutation carriers differs from the general population, even before a cancer diagnosis. Due to the higher likelihood of aggressive disease with poor prognosis, early detection and potentially more aggressive treatment strategies are often recommended.

Studies investigating BRCA2 mutations in familial prostate cancer cohorts have yielded mixed results regarding prevalence, but consistently link these mutations to poorer outcomes [63, 78]. An Australian study found a 4.5 times higher mortality risk for BRCA2 carriers within families featuring multiple breast cancer cases. While BRCA1 mutations are also associated with worse prognosis than non-carriers, the effect appears less pronounced than for BRCA2 [63].

Current NCCN guidelines suggest considering PSA screening starting at age 40 for BRCA mutation carriers [10, 79]. The IMPACT trial demonstrated the potential utility of this approach: using a PSA threshold of >3.0 ng/mL for biopsy, the positive predictive value for detecting prostate cancer was highest among BRCA2 carriers (48%) [10].

Treatment of BRCA Mutation Carriers

Prostate cancer in men with BRCA mutations, particularly BRCA2, warrants a distinct clinical approach. These cancers are often characterized by high Gleason scores (>8), increased likelihood of lymph node metastasis, and poorer prognoses overall [63, 65]. Cancers tend to be diagnosed at a younger age and more advanced stage, with significantly shorter median survival, especially for BRCA2 carriers [[61](#B61], 80]. The poor prognosis associated with BRCA2 persists even after adjusting for pathological features [80]. There is also an association between BRCA2 mutations and the aggressive histological subtype, intraductal carcinoma of the prostate (IDC-P) [81]. Furthermore, dysregulation of the DNA damage response (DDR) pathway, which includes BRCA genes, is linked to significantly worse prognoses in high-risk prostate cancer [82].

Given these factors, active surveillance is generally discouraged for localized prostate cancer in BRCA carriers; aggressive definitive treatment is often preferred. For metastatic disease, therapies targeting the underlying DNA repair defect show promise. Cisplatin-based chemotherapy [83] and PARP inhibitors (like Olaparib) have demonstrated efficacy. A phase II trial showed significant response rates to Olaparib in metastatic castration-resistant prostate cancer (mCRPC) patients with DNA repair gene abnormalities, particularly those with BRCA2 mutations [9]. Subsequent phase III trials confirmed that PARP inhibitors provided longer progression-free survival and better response metrics compared to standard hormonal agents (enzalutamide or abiraterone) in men with mCRPC who had progressed on prior therapy and harbored alterations in homologous recombination repair genes [84].

Conclusions

Extensive population-based evidence confirms significant racial and ethnic disparities in prostate cancer incidence, aggressiveness, and mortality rates across the globe. African-American men consistently face the highest burden, while rates are generally lower among Asian men, though environmental and lifestyle factors influence risk in migrant populations. The determinants underpinning these disparities are complex and multifactorial, involving a combination of socioeconomic factors (access to care, insurance, education), environmental exposures, lifestyle differences, and distinct biological and genetic factors, including variations in tumor genomics and germline mutations like BRCA.

While some data suggest a potential narrowing of survival gaps over time, substantial disparities persist, particularly concerning access to screening, quality of treatment, and outcomes for non-metastatic disease. Understanding the interplay between race, genetics, socioeconomic status, and healthcare access is paramount. Continued research into the biological underpinnings of these differences, coupled with targeted public health initiatives and equitable healthcare policies, is essential to mitigate racial factors associated with adverse outcomes and improve men’s health globally. The knowledge consolidated, reflecting the state of understanding around April 2022, underscores the urgent need for action to achieve health equity in prostate cancer care.