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Ask the Experts – Michael S Leapman
Expert Perspectives
Michael S. Leapman, MD
What is the role of race in prostate cancer treatment decisions?
Michael S. Leapman, MD
Practice Community: New Haven, Connecticut
Hospital and Institutional Affiliations: Assistant Professor of Urology at Yale School of Medicine, New Haven, Connecticut
Number of Patients Seen in a Week: 30
Practice Niche: Urologic oncology
Question 1. Should race enter into treatment decisions? If so, how?
Answer
How race should influence management decisions for prostate cancer is an important and complex issue. To begin with, we know that there are significant differences in cancer incidence and outcome for patients who identify as Black or African American. African Americans continue to have the highest death rate and poorest survival of any racial group in the United States for most cancers, including prostate. African-American men are significantly more likely to be diagnosed with prostate cancer (1 in 6 versus 1 in 8 non-Hispanic Whites), and almost twice as likely to die of the disease (1 in 23 patients diagnosed compared with 1 in 42 non-Hispanic White patients diagnosed). Although it is encouraging that some gaps in outcome appear to be narrowing, there are persistent disparities in rates of definitive treatment for prostate cancer, including for men with intermediate and high-risk cancers.
From this perspective, most clinical guidelines including the National Comprehensive Cancer Network, the American Urological Association, and the American Cancer Society regard African Americans as a high-risk group in which PSA screening should begin earlier. Yet, there is limited evidence to suggest that a patient’s race alone should lead them to be treated differently if prostate cancer is detected. Therefore, it seems that race should be regarded as one of many important variables to consider about an individual’s cancer.
How race should influence management decisions for prostate cancer is an important and complex issue. To begin with, we know that there are significant differences in cancer incidence and outcome for patients who identify as Black or African American. African Americans continue to have the highest death rate and poorest survival of any racial group in the United States for most cancers, including prostate. African-American men are significantly more likely to be diagnosed with prostate cancer (1 in 6 versus 1 in 8 non-Hispanic Whites), and almost twice as likely to die of the disease (1 in 23 patients diagnosed compared with 1 in 42 non-Hispanic White patients diagnosed). Although it is encouraging that some gaps in outcome appear to be narrowing, there are persistent disparities in rates of definitive treatment for prostate cancer, including for men with intermediate and high-risk cancers.
From this perspective, most clinical guidelines including the National Comprehensive Cancer Network, the American Urological Association, and the American Cancer Society regard African Americans as a high-risk group in which PSA screening should begin earlier. Yet, there is limited evidence to suggest that a patient’s race alone should lead them to be treated differently if prostate cancer is detected. Therefore, it seems that race should be regarded as one of many important variables to consider about an individual’s cancer.
Question 2. For you, what stands out as notable differences between whites and blacks with respect to cancer-related clinicopathologic factors?
Answer
Although in aggregate African-American men face greater risks of being diagnosed or dying from prostate cancer, national cancer registry data indicate that the proportion of men diagnosed with localized versus distant disease are actually quite similar. Numerous forces contribute to a patient’s outcome for prostate cancer, including biological factors, the time that their cancer is detected, their diet/lifestyle/exposures, and the treatment they receive. As a result, it has been difficult to determine whether differences in outcome extend from biological differences associated with a patient’s race/ethnicity, or other factors such as lifestyle, socioeconomic status, and treatment preferences.
Yet, complex statistical modeling studies incorporating PSA screening patterns do appear to suggest that African-American men do face higher risks of progression to metastatic disease from pre-clinical prostate cancer. If African-American men do face greater risks of metastatic progression, improving early detection through more thoughtful, tailored screening might be an effective tool to identify and selectively treat high-risk cancers.
Although in aggregate African-American men face greater risks of being diagnosed or dying from prostate cancer, national cancer registry data indicate that the proportion of men diagnosed with localized versus distant disease are actually quite similar. Numerous forces contribute to a patient’s outcome for prostate cancer, including biological factors, the time that their cancer is detected, their diet/lifestyle/exposures, and the treatment they receive. As a result, it has been difficult to determine whether differences in outcome extend from biological differences associated with a patient’s race/ethnicity, or other factors such as lifestyle, socioeconomic status, and treatment preferences.
Yet, complex statistical modeling studies incorporating PSA screening patterns do appear to suggest that African-American men do face higher risks of progression to metastatic disease from pre-clinical prostate cancer. If African-American men do face greater risks of metastatic progression, improving early detection through more thoughtful, tailored screening might be an effective tool to identify and selectively treat high-risk cancers.
Question 3. In your experience, do certain treatments work better in whites vs blacks?
Answer
Whether African-American patients with low-risk prostate cancer are appropriate candidates for active surveillance is a question that is still debated. African-American patients are under-represented in almost all of the large academic cohorts that have longitudinally studied patients on active surveillance, making it difficult to directly compare outcomes over time for patients who choose this approach.
In the absence of direct study, the suitability of active surveillance has been estimated using other surrogate endpoints, such as the likelihood of pathologic upgrading or upstaging. In a cohort of men with very-low risk prostate cancer (defined by Gleason 3+3, PSA density 0.15 ng/mL/cm3 or less, clinical stage T1c or less, 2 or fewer biopsy cores involved, and 50% or less cancer in a given core), who were instead treated with radical prostatectomy, African-American men were significantly more likely to experience pathologic upgrading and positive surgical margins. Moreover, African-American patients who were upgraded at the time of radical prostatectomy were more likely to have dominant, high-grade cancers in the anterior gland that may be missed on standard template biopsy.
Other studies that have examined this question in other databases with a greater representation of African-American patients appear to show no significant associations. Studies addressing the risk of biopsy reclassification over time by race have been performed and appear to indicate greater risks of pathologic progression over time. For example, in a study of the Johns Hopkins active surveillance cohort consisting of 39 African-American men compared with 615 Caucasian men, African-American race was associated with a significantly higher risk of upgrade over time. /div>
Whether African-American patients with low-risk prostate cancer are appropriate candidates for active surveillance is a question that is still debated. African-American patients are under-represented in almost all of the large academic cohorts that have longitudinally studied patients on active surveillance, making it difficult to directly compare outcomes over time for patients who choose this approach.
In the absence of direct study, the suitability of active surveillance has been estimated using other surrogate endpoints, such as the likelihood of pathologic upgrading or upstaging. In a cohort of men with very-low risk prostate cancer (defined by Gleason 3+3, PSA density 0.15 ng/mL/cm3 or less, clinical stage T1c or less, 2 or fewer biopsy cores involved, and 50% or less cancer in a given core), who were instead treated with radical prostatectomy, African-American men were significantly more likely to experience pathologic upgrading and positive surgical margins. Moreover, African-American patients who were upgraded at the time of radical prostatectomy were more likely to have dominant, high-grade cancers in the anterior gland that may be missed on standard template biopsy.
Other studies that have examined this question in other databases with a greater representation of African-American patients appear to show no significant associations. Studies addressing the risk of biopsy reclassification over time by race have been performed and appear to indicate greater risks of pathologic progression over time. For example, in a study of the Johns Hopkins active surveillance cohort consisting of 39 African-American men compared with 615 Caucasian men, African-American race was associated with a significantly higher risk of upgrade over time. /div>
Question 4. Should stricter selection criteria for active surveillance (AS) be applied to Black patients?
Answer
Whether African-American patients with low-risk prostate cancer are appropriate candidates for active surveillance is a question that is still debated. African-American patients are under-represented in almost all of the large academic cohorts that have longitudinally studied patients on active surveillance, making it difficult to directly compare outcomes over time for patients who choose this approach.
In the absence of direct study, the suitability of active surveillance has been estimated using other surrogate endpoints, such as the likelihood of pathologic upgrading or upstaging. In a cohort of men with very-low risk prostate cancer (defined by Gleason 3+3, PSA density 0.15 ng/mL/cm3 or less, clinical stage T1c or less, 2 or fewer biopsy cores involved, and 50% or less cancer in a given core), who were instead treated with radical prostatectomy, African-American men were significantly more likely to experience pathologic upgrading and positive surgical margins. Moreover, African-American patients who were upgraded at the time of radical prostatectomy were more likely to have dominant, high-grade cancers in the anterior gland that may be missed on standard template biopsy.
Other studies that have examined this question in other databases with a greater representation of African-American patients appear to show no significant associations. Studies addressing the risk of biopsy reclassification over time by race have been performed and appear to indicate greater risks of pathologic progression over time. For example, in a study of the Johns Hopkins active surveillance cohort consisting of 39 African-American men compared with 615 Caucasian men, African-American race was associated with a significantly higher risk of upgrade over time.
Whether African-American patients with low-risk prostate cancer are appropriate candidates for active surveillance is a question that is still debated. African-American patients are under-represented in almost all of the large academic cohorts that have longitudinally studied patients on active surveillance, making it difficult to directly compare outcomes over time for patients who choose this approach.
In the absence of direct study, the suitability of active surveillance has been estimated using other surrogate endpoints, such as the likelihood of pathologic upgrading or upstaging. In a cohort of men with very-low risk prostate cancer (defined by Gleason 3+3, PSA density 0.15 ng/mL/cm3 or less, clinical stage T1c or less, 2 or fewer biopsy cores involved, and 50% or less cancer in a given core), who were instead treated with radical prostatectomy, African-American men were significantly more likely to experience pathologic upgrading and positive surgical margins. Moreover, African-American patients who were upgraded at the time of radical prostatectomy were more likely to have dominant, high-grade cancers in the anterior gland that may be missed on standard template biopsy.
Other studies that have examined this question in other databases with a greater representation of African-American patients appear to show no significant associations. Studies addressing the risk of biopsy reclassification over time by race have been performed and appear to indicate greater risks of pathologic progression over time. For example, in a study of the Johns Hopkins active surveillance cohort consisting of 39 African-American men compared with 615 Caucasian men, African-American race was associated with a significantly higher risk of upgrade over time.
Question 5. Should Black men on AS be subject to more frequent follow-up studies (MRIs, biopsies)?
Answer
Currently, it does not seem that there is sufficient evidence to suggest a distinct follow up strategy for African-American patients who are managed with active surveillance. In light of well-established disparities in disease outcome including prostate cancer mortality, it would appear warranted to regard African-American race as a high-risk feature, but not one that should preclude surveillance for well-selected patients.
Strategies to improve selection for active surveillance are rapidly evolving. These include the use of multi-parametric MRI imaging of the prostate, and tissue based genomic testing, which both have been shown to improve estimates of true cancer grade and stage. It is conceivable that improved initial assessment may help determine the aggressiveness of a patient’s cancer. However, additional studies are needed to better understand how these technologies practically improve the selection and outcome of surveillance for African-American men.
Currently, it does not seem that there is sufficient evidence to suggest a distinct follow up strategy for African-American patients who are managed with active surveillance. In light of well-established disparities in disease outcome including prostate cancer mortality, it would appear warranted to regard African-American race as a high-risk feature, but not one that should preclude surveillance for well-selected patients.
Strategies to improve selection for active surveillance are rapidly evolving. These include the use of multi-parametric MRI imaging of the prostate, and tissue based genomic testing, which both have been shown to improve estimates of true cancer grade and stage. It is conceivable that improved initial assessment may help determine the aggressiveness of a patient’s cancer. However, additional studies are needed to better understand how these technologies practically improve the selection and outcome of surveillance for African-American men.
References
Tsodikov A, Gulati R, de Carvalho TM. Is prostate cancer different in black men? Answers from 3 natural history models. Cancer. 2017;123:2312-2319.
Moses KA, Paciorek AT, Penson DF, et al. Impact of ethnicity on primary treatment choice and mortality in men with prostate cancer: data from CaPSURE. J Clin Oncol. 2010;28:1069-1074
Jayadevappa R, Chhatre S, Johnson JC, Malkowicz SB. Variation in quality of care among older men with localized prostate cancer. Cancer. 2011;117:2520-2529.
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;183:1792-1796.
Sundi D, Ross AE, 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;31:2991-2997.
Sundi D, Kryvenko ON, Carter H, et al. Pathological examination of radical prostatectomy specimens in men with very low risk disease at biopsy reveals distinct zonal distribution of cancer in black American men. J Urol. 2014;191:60-67.
Leapman MS, Freedland SJ, Aronson WJ, et al. Pathological and biochemical outcomes among African-American and Caucasian men with low risk prostate cancer in the SEARCH database: Implications for active surveillance candidacy. J Urol. 2016;196:1408-1414.
Jalloh M, Myers F, Cowan JE, et al. Racial variation in prostate cancer upgrading and upstaging among men with low-risk clinical characteristics. Eur Urol. 2015;67:451-457.
Sundi D, Faisal FA, Trock BJ, et al. Reclassification rates are higher among African American men than Caucasians on active surveillance. Urology. 2015;85:155-160.
Kongnyuy M, Sidana A, George AK, et al. The significance of anterior prostate lesions on multiparametric magnetic resonance imaging in African-American men. Urol Oncol. 2016;34:254.e15-21.
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