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.
Published Date: September 11th, 2019
References:
- 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.
- 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.
- 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.
- 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.
- McNamara, George DJ, Ramaswamy K, et al. GCS 2019
- 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).
- 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.
- 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.
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