Anything but Black and White - Racial Disparities in Prostate Cancer

Race is a complex topic in any setting, but in healthcare, it is particularly challenging given the influence of social, lifestyle, and structural determinants associated with racial populations. Make no mistake, race matters in cancer outcomes; in prostate cancer, in particular, year after year black men consistently die at nearly 2.5 times the rate of white men with the same disease.1 To better understand the factors influencing this disparity, Robert Dess and colleagues took a deeper look into prostate cancer-specific mortality (PCSM) by race first through SEER claims data and then through a multi-center Veterans Affairs (VA) prostatectomy cohort and finally through a meta-analysis of radiation-based randomized controlled trials (RCT).2 Their analysis focused on men with localized disease at diagnosis, using propensity modeling to adjust for racial differences, first for the age at diagnosis (black men are diagnosed on average 2-3 years younger) then for co-morbidities and cancer prognostic factors (black men are more likely to have higher stage and grade at diagnosis) and finally for socioeconomic, treatment and insurance status (black men had lower socioeconomic status, were less likely to be treated and were less likely to have insurance).

As expected, black men had a higher PCSM in SEER when adjusted for age (sHR, 1.30; 95% CI, 1.23-1.37; P < .001). In the age- and stage adjusted model, the sHR decreased to 1.17 (95% CI, 1.11- 1.24; P < .001); and in the fully adjusted model, the sHR decreased further to 1.09 (95% CI, 1.04-1.15; P < .001).2 In contrast, in the VA and RCT cohorts there were no statistically significant differences between race and outcomes in the age-adjusted or age and stage adjusted analyses, while in the fully adjusted analysis from the RCT cohort black men actually demonstrated a lower PCSM at 10 years (HR 0.81;95%CI, 0.66-0.99; P = .04). The authors conclude that non-biologic factors account for the differences in outcomes by race.

This analysis adds some important insights into prostate cancer disparity. Clearly, non-biologic factors are key drivers in outcomes. When access is equal, through a single-payer system like the VA or through common participation in clinical trials, the outcome gap largely disappears and may actually swing in favor of black patients. Indeed, we have seen this pattern in other clinical trial settings, demonstrating a survival benefit in favor of black patients of roughly 20% improved survival identified in the fully adjusted RTOG cohort.3-5 Prospectively, we have seen a similar trend in a small pilot study of abiraterone in metastatic castration-resistant prostate cancer in which we hope to explore biologic determinants associated with race and outcome.6 Therefore, to say that biologic factors do not contribute to racial disparity would be an oversimplification. How to we explain these differences biologically, is a different matter. One clue may be in the genetic diversity found with RNA splicing, which is greater blacks than whites and associated with more aggressive disease.7 

The greatest limitation in the analysis by Dess (et al.) was the exclusion of patients presenting with metastatic disease. While this stage accounts for just 5% of newly diagnosed prostate cancer, metastatic prostate cancer is more common in black men and accounts for nearly all the deaths from prostate cancer at 5 years.1 Eliminating this population from the 10-year PCSM creates an incomplete picture at best, and potentially a biased result. In addition, they adjusted for high stage and grade (poor prognostic and biologic factors) at presentation, which is more common in black men with prostate cancer. In essence this adjustment dilutes the aggressive phenotype seen in black men as a population. Interestingly, in a subgroup analysis, Dess et al reported that black men with low and intermediate risk disease had higher PCSM compared to white men, while in the high risk subgroup PCSM was the same, again suggesting that unknown biologic factors may be associated with race and low/intermediate risk disease. Similarly, Mahal et al. identified a nearly 2 fold greater likelihood of black men dying from low grade prostate cancer compared to white men.8

Ultimately, efforts to address access differences by race will have the greatest impact on closing the disparity gap, but understanding biologic differences associated with racial diversity among prostate cancer patients could lead to more precise management for all patients.


Written by: Daniel J. George, MD, Medical Oncologist, Professor of Medicine, Professor of Surgery, Duke Cancer Institute, Durham, North Carolina.

References:
  1. DeSantis CE, Siegel RL, Sauer AG, et al. Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities. CA Cancer J Clin. 2016 Jul;66(4):290-308. doi: 10.3322/caac.21340.
  2. Dess RT, Hartman HE, Mahal BA, et al. Association of Black Race With Prostate Cancer-Specific and Other-Cause Mortality. JAMA Oncology. 2019 May 23. Jul 1;5(7):975-983. doi: 10.1001/jamaoncol.2019.0826.
  3. Halabi S, et al. Overall Survival of Black and White Men With Metastatic Castration-Resistant Prostate Cancer Treated With Docetaxel. Journal of Clinical Oncology. 2018 Feb 10;37(5):403-410. doi: 10.1200/JCO.18.01279. 
  4. Quinn DI, Freedland SJ, Heath EI, et al. Survival outcomes for African-American (AA) vs matched Caucasian (CAU) patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T (sip-T). Journal of Clinical Oncology. 2017;35:6_suppl:192.
  5. McNamara, George DJ, Ramaswamy K, et al. GCS 2019
  6. George DJ, Heath EI, Sartor AO, et al. Abi Race: A prospective, multicenter study of black (B) and white (W) patients (pts) with metastatic castrate resistant prostate cancer (mCRPC) treated with abiraterone acetate and prednisone (AAP). Journal of Clinical Oncology. 2018;36(18)(suppl).
  7. Wang, Bi-Dar et al. 2017. "Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer". Nature Communications 8 (1). Springer Science and Business Media LLC. doi:10.1038/ncomms15921.
  8. Mahal, Brandon A. et al. 2018. "Prostate Cancer–Specific Mortality Across Gleason Scores in Black vs Nonblack Men". JAMA 320 (23): 2479. American Medical Association (AMA). doi:10.1001/jama.2018.11716.
Related Content: 
Watch: Disparities in Prostate Cancer Management in the United States Presentation - Alicia Morgans
Read: ASCO 2019: From Trials to Treatment: Addressing Disparities in Access to Prostate Cancer Care
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