According to the SEER Statistics data, five-year relative survival by race is 99.6% for Caucasian men and 95.9% for African American men [2
]. Moreover, age-adjusted PCa related mortality is two to three fold higher for African American, compared to Caucasian, men [1
]. In addition to worse overall survival and higher mortality rates, African American patients treated for PCa exhibit diminished general outcomes and quality of life (QOL) after PCa treatment, compared to Caucasians [64
]. The causes of this aspect of PCa racial disparity are obscure, and research evidence is conflicting. Some researchers attribute the racial disparities in survival to Socio-Economic factors. For example, Tewari et al [56
] explored the effect of socioeconomic factors on long-term mortality in men with clinically localized PCa. In this study, African American patients were more likely to have lower incomes, a greater baseline PSA level, and greater comorbidities. In addition, African American men had significantly increased cancer-specific (hazard ratio 1.47) and overall (hazard ratio 1.29) mortality. However, after adjusting for health insurance status and SES, the differences disappeared (adjusted hazard ratios 1.04 and 0.96, respectively). The authors concluded that, in their cohort, socioeconomic factors were sufficient to explain the disparity in survival. Schwartz et al [54
] explored the influence of race, SES, and treatment on survival of patients with PCa. In this study, a greater SES for both localized and regional stage PCa was associated with longer overall and cancer-specific survival in the African American population. Older age and poorly differentiated tumor grade predicted poor survival but did not explain the racial difference; however, the adjustment for SES eliminated much, if not all, of the racial difference in overall and cancer-specific survival among men with localized or regional stage PCa.
The finding of substantial influence of SES on the survival and quality of life, however, was not supported by Dash et al [66
] who examined an impact of socioeconomic factors on PCa outcomes in African American patients treated with surgery, in a cohort of 430 African American men. The authors concluded that there was minimal impact of income and/or education on PSA recurrence in their cohort. After controlling for race by studying a large and diverse cohort of African American men treated by radical prostatectomy, the primary finding was that neither income nor education had a statistically significant effect on recurrence-free survival. In further support of these findings, Halbert et al [67
] examined the quality of life following PCa diagnosis in African American and Caucasian men when controlling for perceived stress and the level of religiosity. The sample consisted of 194 men: 66 African Americans and 128 Caucasians. The authors report no significant effect of the socioeconomic factors on emotional or physical functioning. However, several other important findings were noted: 1. African American men reported better emotional well-being compared with Caucasian men. The authors hypothesized that African American men are exposed to a greater number of adverse life events, and these experiences may reduce the threat of being diagnosed with PCa. 2. Religiosity did not have a significant effect on emotional or physical wellbeing of African American patients. This could be because the measure of religiosity did not evaluate whether the religious beliefs were actually used to cope with the diagnosis. 3. Subjective stress had a significant adverse effect on emotional and physical well-being. The authors concluded that helping men to identify specific sources of stress and use coping strategies that are most likely to be effective at managing these issues may reduce levels of stress and enhance the quality of life. This finding was supported by Purnell et al [68
] who have recently reported significantly higher levels of traumatic stress for African American PCa survivors compared to non-African American survivors. The authors analyzed 317 men (African American: n
= 30, 9%; non-African American: n
= 287, 91%) who were enrolled in the 24-months intervention trial, and found that racial disparity in traumatic stress persisted even after adjustment for all major covariates, indicating that this particular population may be under higher levels of psychological distress, which may negatively impact survival. In contrast to this last findings of Halbert et al [67
] and Purnell et al [68
], Hyacinth et al [69
] reported no significant influence of stress on the QOL of PCa survivors in a cohort of 136 men (5% African Americans). The analysis revealed that survivors were experiencing low levels of stress which had only marginal influence on the overall quality of life. However, the study included only 5% African Americans, and it is possible that Caucasians and African Americans perceive stress differently. It is also possible that the time from the initial diagnosis to some extent alleviated the level of perceived stress, associated with PCa. Besides stress, which was insignificant in this study, the authors noted complaints of sexual, bowel and bladder problems in all races, including African Americans. It was not reported by Hyacinth et al [69
] whether these problems are more pronounced in African American men, compared to Caucasians, however, Ukoli et al [70
] have examined the cohort of African American men who underwent radical prostatectomy in the SEER historical database. The authors found that sexual and urinary symptoms, bone pain, fatigue and emotional distress all were significantly associated with radical prostatectomy in most African American men. It was concluded that expected benefits and side effects of radical prostatectomy, specifically tailored towards African American population, should be carefully weighed before the treatment decision is made. Similar results were also reported by Stanford et al [71
]. These latter findings emphasize the need to conduct additional research among PCa survivors of African descent, aimed to tease out the benefits of a radical prostatectomy in terms of survivorship and longevity-promotion, versus possible significant side effects and substantially diminished quality of life following surgery in this particular population. In contrast to the findings reported by Halbert et al [67
], Hamilton et al [72
] and Zavala et al [73
] emphasized on the exceptional role of the religious life and faith have on African American patients with PCa. The authors recommended that physicians and other medical personnel have to understand and support the unique relationship their African American patients may have with God, as this will improve both physical and emotional well-being and promote survival.
Penedo et al [42
] have explored ethnicity and QOL after PCa treatment in a diverse sample of 204 men (85 Caucasian, 37 African American, and 82 Hispanic). In this sample, the relationship between ethnicity and QOL appeared to be significantly accounted for by sociodemographic, medical, and health behavior factors. Health behaviors related to sleep and physical activity demonstrated a robust association with QOL, suggesting that differences in these categories may be one of several mechanisms that may explain ethnic disparities in QOL. Ethnic group membership was related to QOL such that minority men had lower QOL than Caucasian men. Three variables - medical comorbidity, physical activity, and sleep functioning - remained significant and explained 37% of the variance in quality of life scores.
Peay et al [53
] have evaluated the health-related QOL after treatment for PCa in African American and Caucasian groups totaling 665 men (32% African American). It was found that at 12 months, African Americans who underwent external beam radiation had significantly lower mean urinary function scores than Caucasians undergoing external beam radiation, while African Americans choosing surgery had significantly lower mean physical function scores than Caucasians undergoing surgery. The reasons for these preferences are not known. In addition, authors concluded that special attention should be paid to the reason for selection of external beam radiation among African American men and how this might impact long term urinary function.
Biochemical recurrence of PCa after radical prostatectomy, defined as a PSA of at least 0.4ng/ml followed by another increase, is an important determinant of survival and QOL, as rising PSA level is the first sign of ultimate progression to distant metastasis [74
]. Hamilton et al [75
] explored if African American men are at higher risk of biochemical PCa recurrence after radical prostatectomy. 1612 men (41% African American), were followed retrospectively for 50 months, and disease recurred in 488 men (31%), 265 of whom were Caucasian (29%) and 223 of whom were African American (34%). Although race was found to be significantly correlated with biochemical disease recurrence, with African American men being at an increased risk (hazard ratio 1.28), there was no significant difference noted with regard to the mean time to disease recurrence, and the PSA doubling time at the time of disease recurrence was found to be similar between the races. The authors concluded that continued work is needed to reduce the number of disease recurrences in the high-risk group of African Americans. Similar findings were also reported by Grossfeld et al [76
] who examined a multiracial cohort of 1,468 patients following radical prostatectomy at the University of California. Overall, disease recurred in 21% of the patients, and African American race, serum PSA at diagnosis, biopsy Gleason score and percent positive prostate biopsies were independent predictors of recurrence. Estimated 5-year disease-free survival was 65% and 28% in Caucasian and African American men, respectively. However, when education and income were entered into the multivariate model, ethnicity was no longer an independent predictor, suggesting that socio-economic factors may be important contributors in the poorer outcomes among African American patients after radical prostatectomy.
Caire et al [77
] explored the relationship between obesity and risk of pathological features and a greater risk of PSA recurrence in African American men in a cohort of 4196 consecutive patients who underwent radical prostatectomy from 1988 to 2008, retrieved from the Duke Prostate Center database. Obese African American men in this study had higher-risk disease characteristics and a greater risk of PSA recurrence despite controlling for PSA level and clinical tumor stage. SES might also play a role, as African American men might have limited access to healthcare and not attend for follow-up as frequently after diagnosis. Furthermore, a greater proportion of African American men were obese in the present cohort. Similar findings were reported by Spangler et al [78
], who reported that obesity was associated with poorer tumor characteristics (OR 2.30, 95% CI 1.04–5.1), and greater likelihood of treatment failure and biochemical recurrence (adjusted hazard ratio 5.49, 95% CI 2.16–13.9) in African American, but not Caucasian men. Obesity is a modifiable risk factor that might be associated with more aggressive tumor biology, possibly mediated through increased leptin levels in obese men. Leptin is a protein hormone that is responsible for increased metabolism and decreased appetite. Leptin was reported to exhibit mitogenic effects on various cancer cell lines, including prostate [79
], breast [80
] and colorectal cancers [81
] through MAPK and PI3-K pathways, thus promoting angiogenesis and facilitating proliferation. In addition to leptin, obesity may promote PCa progression through overexpressed markers of inflammation (IL-6, TNG-a), reduced plasma adiponectin levels (thus increasing the leptin/adiponectin ratio, favoring proliferation), and acquired insulin resistance [82
]. Thus far, racial variations in systemic levels of mentioned above biomarkers and the degree of their implication in PCa disparity are still under exploration; however, taken together, the study suggests obesity might be responsible for the racial disparity seen in PCa. In addition to obesity, dietary factors have been shown to correlate with PCa initiation and progression, with increased animal fat, cooked red meat and dairy consumption being the most studied dietary risk factors [83
]. It was reported that African Americans tend to maintain high-fat diets more often than any other racial groups [12
], thus possibly facilitating the disparity in PCa initiation, progression and survival. Extensive research aimed to explore the role of dietary patterns in overall PCa risk and its relation to disparity is currently ongoing.
Thompson et al [85
] have used the data from 288 African American and 975 Caucasian men in the randomized phase III trial that compared orchiectomy with or without flutamide in men with metastatic PCa, to determine if race was an independent predictor of survival. After adjustment for the most important prognostic variables (more extensive disease, younger age and higher Gleason score in African Americans), the hazard ratio for all cause mortality for African American men versus Caucasian men was 1.23. Disease extent, presence of bone pain, Gleason score of 8–10, and the general health status measures all were statistically significant, independent predictors of overall survival. After adjustment for these measures, African- American race was determined to be associated with even higher risk of death (hazard ratio 1.39).
The influence of co-morbid conditions on post-treatment QOL and PCa related mortality in men of different races was examined by Holmes et al [86
]. The authors reported that African American men usually present with a greater comorbidity index (9% vs 4.6% Caucasian men). This factor contributes to worse treatment outcomes and racial disparity in survival ; when comorbidities are controlled for, these disparities disappear (hazard ratio = 0.98; confidence interval 0.94–1.03). It was also noted that, despite marked race-related differences in treatment, adjusting for this difference has little effect on survival. Putt et al [87
] have examined the influence of comorbidities on the survival of elderly Medicare PCa patients in the sample of over 55,500 men. For both races, greater comorbidity was associated with decreased survival rates; however, the effect among African Americans was smaller than in Caucasians, and racial disparity in survival decreased with increasing number of comorbidities. Adjusting for treatment had little impact on these results. Racial disparities are most pronounced between African American and Caucasian men with no or few comorbidities and are not evident at higher levels of comorbidity. The reasons for this effect are unknown, however, the authors suggested that either African Americans with greater comorbidities may have died before PCa diagnosis (which is usually made in the 60s or 70s), or if PCa is more aggressive in African Americans, they are more likely die of it rather than of co-morbid conditions. A larger competing risk of death from PCa among African American men than Caucasian men could result in a smaller effect of comorbidities on overall survival. It is also possible that African American men are overall less susceptible to death caused by co-morbid conditions, compared to Caucasian men, and therefore at higher levels of co-morbidities, the rate of PCa attributed death in African American men is balanced by the rate of death in Caucasian men, caused by co-morbid factors, unrelated to PCa. Such “balancing” may be responsible for an overall alleged reduction in PCa racial disparity. While intriguing, these rationales are yet speculative and require additional transdisciplinary research, involving clinicians, epidemiologists, biostatisticians, behavioral scientists, and psychologists to rule out the definite conclusion.
The worse overall outcomes in African American men with PCa result in increased healthcare resource use and cost, as reported by multiple works published by Jayadevappa et al [88
]. It was found that not only do African American patients have higher care cost for PCa at all levels (except the terminal phase where no substantial difference was noted), but that also the incremental cost of PCa care was higher for the African American group. In addition, African American men were more likely to have emergency room visits, while Caucasian men utilized mostly outpatient visits, and the mean length of hospital stay was longer among African American men during all phases of care. In addition, African American men receiving treatment in the medium size hospitals were found to accrue higher cost (odds ratio = 1.53 compared to Caucasian men), but worse immediate post-treatment outcomes as defined by increased complications (odds ratio = 1.39 compared to Caucasian men) and greater co-morbidity [89
]. Interestingly, this association was not observed for big and small hospitals, and is attributed to the limited amount of resources and lack of diversity that may be observed in a medium-sized hospitals. The authors concluded that any health-policy measures aimed at effectively reducing racial and ethnic disparity in care should address the issues related to variation in health resource usage and associated cost.
The latter was also supported by Keating et al [90
], Haas et al [91
] and Smith et al [92
], who reported an underuse of hospice services by African Americans with any cancer, including PCa, at the end of live. This aspect of the racial disparity is of particular concern, because the hospice use is associated with the reduced number of emergency room visits, decreased pain and suffering, and enhanced overall emotional and physical well-being of PCa patients at the end of life. The reasons for this disparity are not well understood and require further research, which should also explore the ways of promoting the hospice use among African American men and men of other minority groups, dying of PCa.
In contrast to previous reports, Klein et al [93
] in their recent review come to a conclusion that if localized PCa is treated adequately and appropriately, patients do equally well across all stages, regardless of race or ethnicity. Survival outcomes were equivalent between Caucasians and African Americans when treatment was assigned in a uniform manner without regard to race. A similar conclusion was drawn by Merrill et al [94
], who examined PCa data from the SEER Program. The authors reported no differences in PCa related mortality between races after adjusting for differences in stage and grade, age, number of primary cancers, and treatment. It was concluded that later stage at diagnosis is the primary reason for the higher likelihood of PCa mortality among black men compared to white men. Resnick et al [95
] retrospectively reviewed the database of 2407 patients who under went radical prostatectomy and concluded that no significant difference was found in PCa-specific measures of disease control, risk of disease upgrading, estimated tumor volume, or recurrence-free survival between Caucasian and African American men. The authors noted that, despite the well-documented racial disparities in PCa epidemiology and outcomes, no evidence exists that clinically-determined low-risk African American patients are at increased risk of advanced disease at radical prostatectomy.
Although studies demonstrate significant racial disparities of biological and socio-cultural nature, affecting PCa survivors of African descent, additional research is needed to establish their causes and outline intervention aimed to minimize them.