Active Surveillance for African-American Men With Prostate Cancer: Proceed With Caution

Results of recent randomized trials suggest that prostate cancer may be overtreated, especially in older men and those with low-grade (Gleason score ≤ 6) disease.[1,2] In older men, indolent cancers may never become clinically apparent in their lifetimes. This notion is supported by outcomes of active surveillance (AS) programs, in which men with characteristics of low-risk disease are closely monitored by periodic digital rectal exams, prostate-specific antigen (PSA) blood tests, and prostate biopsies-with curative management deferred until there is evidence of disease progression, such as detection of high-grade cancer on serial biopsy. In the major AS programs, oncologic outcomes are quite favorable, with prostate cancer–specific mortality of 0% to 1% with up to 7 years of follow-up.[3]

However, it is incorrect to generalize these results to men of all races. Outcomes of AS are based predominantly on data in white men; minorities are severely underrepresented, with black men comprising 6% to 10% of the cohorts at best. Moreover, there are differences in prostate cancer incidence and mortality across different populations worldwide, implicating race and genetics as important determinants.[4,5] In particular, prostate carcinogenesis and progression in African-American men may be molecularly distinct, as shown by differential expression of ERG and inflammatory cytokines such as CXCR4.[6,7] In fact, there are marked clinical disparities when comparing African-American and white men with prostate cancer. Based on a study of national cancer registry and autopsy data, investigators have deduced that prostate cancer growth and progression may be significantly faster in African-American men.[8] Stage-for-stage, African-American men undergoing radical prostatectomy have higher tumor volumes,[9] and they tend to present with more advanced disease and have decreased survival after treatment.[10]

These findings present a dilemma: AS seems to be generally safe, yet African-American men tend to have more aggressive prostate cancers. Thus, it is imperative that we learn the characteristics and outcomes of African-American men considering AS. These have recently come to light: studies of the University of Miami and Duke University AS cohorts have shown that African-American men on AS are over three times more likely than white men to suffer disease progression (detection of high-grade or high-volume cancers) on serial biopsies.[11,12]

We studied the Johns Hopkins surgical cohort of men who met all National Comprehensive Cancer Network (NCCN) criteria for very-low-risk disease (Gleason ≤ 6, clinical stage T1c, ≤ 2 positive cores, ≤ 50% cancer involvement/core, PSA level ≤ 10 ng/mL, and PSA density ≤ 0.15 ng/mL/cc) and who were diagnosed in the modern Gleason grading era (2004 or later) with extended biopsy sampling. These men would all have qualified for AS, but they chose to undergo immediate radical prostatectomy. We found that the African-American men in this cohort were significantly more likely than whites to be upgraded to Gleason ≥ 7 at surgery (33% vs 13%) and to have adverse pathologic features, as evidenced by Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score ≥ 3 (21% vs 6%) and positive surgical margins (19% vs 6%).[13] These results confirm a smaller report of men with clinical stage T1c disease who underwent surgery, where among men with Gleason ≤ 6 disease on biopsy, the rate of upgrading at prostatectomy was 62% for African-American men vs 10% for white men.[14] Further, results from the Johns Hopkins AS cohort demonstrate that African-American men are over two times more likely than whites to progress to high-grade disease on serial biopsy (manuscript in preparation).

We also performed a pathologic analysis of surgical specimens of the men in the Johns Hopkins surgical cohort who would have qualified for AS, and we found that African-American men were 22% to 59% more likely to harbor dominant tumor nodules in the anterior aspect of the prostate gland, especially in the setting of high-grade disease.[15] This finding adds to the complexity of AS for African-American men, given that dominant tumor nodules are more likely to be in the anterior aspect of the prostate gland, a difficult location to sample with standard biopsy technique (which uses a posterior approach). It is not known whether prostate imaging performed in African-American men who are AS candidates will be able to detect large anterior tumor nodules in order to aid risk stratification, although this question merits prospective evaluation.

It is troubling that current risk-stratification tools are inaccurate when applied to African-American men. Men with favorable-risk prostate cancer who enroll in AS programs generally have acceptable oncologic outcomes, but African-American men have a distinct, elevated risk profile, which may be tied to innate differences in cancer biology and/or tumor location. Even among men who meet NCCN very-low-risk criteria, African-Americans are approximately two to three times more likely to harbor undetected high-grade disease and adverse pathologic features at surgery, and to demonstrate progression to high-grade disease on serial biopsy. This is not to say that AS is contraindicated for African-American men. However, AS in African-Americans should be undertaken with substantial caution and only after the patient is counseled about his elevated oncologic risks. ❍

Financial Disclosure:The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Schröder FH, Hugosson J, Roobol MJ, et al. Prostate-cancer mortality at 11 years of follow-up. N Engl J Med. 2012;366:981-90.

2. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2013;367:203-13.

3. Dall’era MA, Albertsen PC, Bangma C, et al. Active surveillance for prostate cancer: a systematic review of the literature. Eur Urol. 2012;62:976-83.

4. Quinn M, Babb P. Patterns and trends in prostate cancer incidence, survival, prevalence and mortality. Part I: international comparisons. BJU Int. 2002;90:162-73.

5. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095-128.

6. Rosen P, Pfister D, Young D, et al. Differences in frequency of ERG oncoprotein expression between index tumors of Caucasian and African American patients with prostate cancer. Urology. 2012;80:749-53.

7. Powell IJ, Dyson G, Land S, et al. Genes associated with prostate cancer are differentially expressed in African American and European American men. Cancer Epidemiol Biomarkers Prev. 2013;22:891-7.

8. Powell IJ, Bock CH, Ruterbusch JJ, Sakr W. Evidence supports a faster growth rate and/or earlier transformation to clinically significant prostate cancer in black than in white American men, and influences racial progression and mortality disparity. J Urol. 2010;183:1792-6.

9. Moul JW, Sesterhenn IA, Connelly RR, et al. Prostate-specific antigen values at the time of prostate cancer diagnosis in African-American men. JAMA. 1995;274:1277-81.

10. Chornokur G, Dalton K, Borysova ME, Kumar NB. Disparities at presentation, diagnosis, treatment, and survival in African American men, affected by prostate cancer. Prostate. 2011;71:985-97.

11. Iremashvili V, Soloway MS, Rosenberg DL, Manoharan M. Clinical and demographic characteristics associated with prostate cancer progression in patients on active surveillance. J Urol. 2012;187:1594-9.

12. Abern MR, Bassett MR, Tsivian M, et al. Race is associated with discontinuation of active surveillance of low-risk prostate cancer: results from the Duke Prostate Center. Prostate Cancer Prostatic Dis. 2013;16:85-90.

13. Sundi D, Ross AD, Humphreys EB, et al. African American men with very low-risk prostate cancer exhibit adverse oncologic outcomes after radical prostatectomy: should active surveillance still be an option for them? J Clin Oncol. 2013;31:2991-7.

14. Sanchez-Ortiz RF, Troncoso P, Babaian RJ, et al. African-American men with nonpalpable prostate cancer exhibit greater tumor volume than matched white men. Cancer. 2006;107:75-82.

15. Sundi D, Kryvenko ON, Carter HB, et al. Pathological examination of radical prostatectomies in men with very low risk disease at biopsy reveals distinct zonal distribution of cancer in black American men. J Urol. 2013 Jun 14. [Epub ahead of print]