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Beyond the Abstract - Impact of race on disease recurrence following prostate Brachytherapy, by Kosj Yamoah MD., PhD

BERKELEY, CA (UroToday.com) - Background
Globally, black men are known to experience greater incidence and mortality from prostate cancer. A number of factors contributing to this trend include inadequate access to healthcare, low socioeconomic factors, and race/ethnicity.

  Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) and the Duke Prostate Center (DPC) databases showed that despite favorable clinical or pathological staging and low risk disease at time of diagnosis, African-American (AA) men were found to be at an increased risk of biochemical disease recurrence [1]. Much work done regarding the effect of race on biochemical disease recurrence after treatment has focused on extent external beam radiotherapy [2-6]. However, results from these studies have proven inconclusive as a result of conflicting data likely due to differences in selection criteria and inadequate sample size in the AA population.

 

Findings
Published data on the influence of race on outcome in patients undergoing permanent prostate seed implantation/brachytherapy, a common form of therapy for prostate cancer, is very sparse. In the current article by Yamoah et al, the authors examine the impact of race on biochemical disease-free survival in patients treated with prostate brachytherapy [7]. To date, this article provides one of the largest series on the impact of race on outcomes among AA patients treated with prostate brachytherapy. A total of 2301 patients, 12% AA, treated at a single institution from June 1990 to October 2008 were identified. Patients were treated with low-dose-rate prostate brachytherapy (seed implants) +/- EBRT with or without androgen depravation therapy (ADT). In this study population, AA men demonstrated a significantly lower 10-year biochemical disease-free survival, compared to Caucasians; 70% and 83% respectively. Consistent with previous reports [1, 8-10] this study showed that AA men present at an earlier age and higher initial PSA as compared to their Caucasian counterparts. Additionally, AA men presented with higher risk disease as compared to Caucasian men; 24% and 15% respectively. Within the low risk category AA men demonstrated a significantly lower 10-year freedom from biochemical failure (FFbF) of 70%, compared to 90% in Caucasians. Interestingly, the most significant difference in biochemical disease-free survival (86% Caucasian and 61% AA) occurred in the treatment group receiving seed implants only, >95% of which were in the low-risk category. However, upon adding ADT or EBRT to seed implantation, the observed difference in biochemical disease recurrence between race groups was abrogated. Furthermore, although the demographic data indicated that more AA men presented with higher risk disease as a result of higher initial PSA levels, there was no difference in 10-year biochemical failure rates among Caucasians and AA men with high risk disease. These findings showed that AA men receiving more aggressive treatment options achieved biochemical disease-free survival rates comparable to that of Caucasian men. The article also demonstrated an increase in biochemical disease recurrence among patients receiving BED ≤200 as compared to BED >200. This difference was more robust in AA as compared to Caucasian men. In summary, results from this study suggest that AA men are predisposed to a significantly higher risk of biochemical failure, which may warrant a more aggressive therapy to achieve effective local control and decrease biochemical disease recurrence. It is worthwhile to mention that the observed difference in biochemical disease recurrence among the race groups did not directly correlate with clinical endpoints such as overall survival, cause-specific survival or distant metastasis-free survival rates. It would be interesting to determine whether the increased biochemical disease recurrence among AA men might lead to more frequent salvage therapy in this patient population.

Genomic studies on racial disparity in prostate disease
Racial differences in genetic and/or physiologic factors may play a role in prostate disease characteristics, progression and treatment response. Much work done regarding prostate cancer disease presentation and treatment response has been primarily conducted on subjects of European ancestry. However, there is an increased awareness of the fact that results obtained from one ethnicity may not necessarily apply to individuals from a different ethnic origin. A number of genes involved in the androgen pathway have been shown to exhibit racial variations. AA men have been shown to have distinct polymorphisms in the androgen receptor classified as a greater percentage of short CAG repeats that may be associated with increased androgen sensitivity at any given testosterone hormone level [11, 12]. Other groups have demonstrated racial differences in the CYP3A4 gene responsible for testosterone metabolism [13, 14]. However, a distinct correlation with survival of men treated for localized prostate cancer with EBRT +/- ADT using patients from the RTOG 9202 Phase III randomized trial could not be established[14]. Recently, a genome-wide association study (GWAS), with 1,047,986 SNP markers was examined in a consortium of prostate cancer studies that included men of African ancestry [15]. They identified a new marker of risk for prostate cancer on chromosome 17q21 that appears specific to men of African descent. Further studies on this allele are needed to understand its biological contribution to the increased incidence and mortality of prostate cancer in this patient population. Similarly, another GWAS study in AA men receiving treatment for prostate cancer identified a single nucleotide polymorphism (SNPs) most strongly associated with the development of erectile dysfunction after radiotherapy [16]. To further emphasize the importance of this study design is the identification of four SNPs that were specific to persons of African ancestry, which would have been missed had a cohort of European ancestry been screened.

Conclusion
The influence of genetic predisposition such as race/ethnicity on prostate cancer in men pre- and post-treatment has been under intense scrutiny over the past two decades. The way of the future in search to understand the genetic or physiologic factors that contribute to high rates as well as poor progression-free survival in men of African ancestry with prostate cancer should be aimed at conducting studies in cohorts of pure African descent to identify gene-specific factors and investigate the mechanism whereby they may con¬tribute to the racial disparity in prostate cancer manifestation and/or treatment response.

 

References:

  1. Moreira, D.M., et al., The effect of race on the discriminatory accuracy of models to predict biochemical recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital and Duke Prostate Center databases. Prostate Cancer Prostatic Dis, 2010. 13(1): p. 87-93.
  2. Rosser, C.J., et al., Racial influence on biochemical disease-free survival in men treated with external-beam radiotherapy for localized prostate cancer. J Natl Med Assoc, 2004. 96(7): p. 939-44.
  3. Hamilton, R.J., et al., Race, biochemical disease recurrence, and prostate-specific antigen doubling time after radical prostatectomy: results from the SEARCH database. Cancer, 2007. 110(10): p. 2202-9.
  4. Powell, I.J., et al., Prostate cancer biochemical recurrence stage for stage is more frequent among African-American than white men with locally advanced but not organ-confined disease. Urology, 2000. 55(2): p. 246-51.
  5. Zagars, G.K., A. Pollack, and C.A. Pettaway, Prostate cancer in African-American men: outcome following radiation therapy with or without adjuvant androgen ablation. Int J Radiat Oncol Biol Phys, 1998. 42(3): p. 517-23.
  6. Nielsen, M.E., et al., Black race does not independently predict adverse outcome following radical retropubic prostatectomy at a tertiary referral center. J Urol, 2006. 176(2): p. 515-9.
  7. Yamoah, K., N. Stone, and R. Stock, Impact of race on biochemical disease recurrence after prostate brachytherapy. Cancer, 2011.
  8. Zietman, A., et al., The Patterns of Care Survey of radiation therapy in localized prostate cancer: similarities between the practice nationally and in minority-rich areas. Int J Radiat Oncol Biol Phys, 2001. 50(1): p. 75-80.
  9. Roach, M., 3rd, et al., The prognostic significance of race and survival from prostate cancer based on patients irradiated on Radiation Therapy Oncology Group protocols (1976-1985). Int J Radiat Oncol Biol Phys, 1992. 24(3): p. 441-9.
  10. Vijayakumar, S., et al., Prostate-specific antigen levels are higher in African-American than in white patients in a multicenter registration study: results of RTOG 94-12. Int J Radiat Oncol Biol Phys, 1998. 40(1): p. 17-25.
  11. Coetzee, G.A. and R.K. Ross, Re: Prostate cancer and the androgen receptor. J Natl Cancer Inst, 1994. 86(11): p. 872-3.
  12. Powell, I.J., et al., The impact of CAG repeats in exon 1 of the androgen receptor on disease progression after prostatectomy. Cancer, 2005. 103(3): p. 528-37.
  13. Wandel, C., et al., CYP3A activity in African American and European American men: population differences and functional effect of the CYP3A4*1B5'-promoter region polymorphism. Clin Pharmacol Ther, 2000. 68(1): p. 82-91.
  14. Roach, M., 3rd, et al., Racial differences in CYP3A4 genotype and survival among men treated on Radiation Therapy Oncology Group (RTOG) 9202: a phase III randomized trial. Int J Radiat Oncol Biol Phys, 2007. 69(1): p. 79-87.
  15. Haiman, C.A., et al., Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21. Nat Genet, 2011. 43(6): p. 570-3.
  16. Kerns, S.L., et al., Genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men after radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys, 2010. 78(5): p. 1292-300.

 

Written by:
Kosj Yamoah MD., PhD. as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Impact of race on survival in patients with clinically nonmetastatic prostate cancer who deferred primary treatment - Abstract

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