BERKELEY, CA (UroToday.com) - Prostate cancer (PCa) is the most common non-cutaneous malignancy in men and is diagnosed in over 230 000 men annually in the U.S. alone. PCa is also the second leading cause of cancer deaths, about 30 000 per year in the U.S. But as evidenced by this large gap in annual incidence and mortality, PCa is often not lethal. Sorting out which new cases are lethal vs indolent is the major challenge facing PCa researchers today. Meanwhile, many men with PCa undergo radical curative treatments such as radical prostatectomy (RP) or radiation therapy in the face of uncertainty regarding the lethal potential of their cancers, even though in a large number of cases the PCa is indolent and would not have caused a patient’s death before death from another cause. This concept is called overtreatment, and leading epidemiologists report that overtreatment is a central dilemma in PCa, with up to two-thirds of newly diagnosed cases potentially affected by overtreatment.
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A strategy to reduce overtreatment is active surveillance (AS), where men with low-risk characteristics are carefully monitored over time with intermittent prostate specific antigen (PSA) tests and prostate needle biopsies. Men are considered to demonstrate PCa progression when they develop worrisome disease features over time (disease progression in terms of biopsy Gleason grade sum increasing from 6 to ≥7 or increase in the number of biopsy cores involved with cancer, for example). Patients who maintain low-risk features over time simply continue on AS, while patients with signs of cancer progression are offered curative treatment. Overall, the survival outcomes of AS programs are superb, with PCa-specific mortality rates usually well under 1%, which supports the safety of AS as potential answer to PCa overtreatment.
There is a caveat, however. AS has only been well studied in predominantly white American or white European cohorts, but it is well known that black men are at much higher risk of both developing and dying from PCa. In a large study of patients from Johns Hopkins who underwent RP but would have been eligible for AS, we found that black men, compared to white men, were at significantly higher risk for harboring large tumor nodules with high Gleason grade, and that these worrisome tumor nodules tended to escape detection by pre-treatment biopsy due to a tendency to grow in the anterior zone of the prostate, which is difficult to sample with standard biopsy techniques. Confirming our findings, a separate recently published study from the University of Pennsylvania also shows that AS-eligible black men are at higher risk for adverse pathologic features. Furthermore, a recently published national epidemiologic study showed that black men with low-risk PCa (the group of men thought to be good AS candidates) are at significantly higher risk of suffering death from PCa than white men.
Given these concerning discoveries, we sought to study racial disparities among men enrolled in the AS program at Johns Hopkins. We found that black men were 2-3 times more likely to demonstrate disease progression on serial biopsy, and that the major reason for this was an increase to high grade (Gleason ≥7) PCa over time (see Figure).
These study results are in line with reports from earlier, smaller cohorts.[10, 11] Taken together, these findings suggest that AS should not be a one-size-fits-all prescription. While AS is an important alternative to RP and radiation therapy, and therefore can help reduce the problem of PCa overtreatment, it must be carefully and selectively applied, especially in black men. Long-term race-specific oncologic outcomes of men on AS (such as metastasis and cancer-specific mortality) must be carefully studied, and the safety of alternate race-specific entry criteria for AS programs must be cautiously evaluated.
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- Loeb S, Bjurlin MA, Nicholson J, Tammela TL, Penson DF, Carter HB, et al. Overdiagnosis and overtreatment of prostate cancer. Eur Urol 2014;65:1046–55.
- Dall’era MA, Albertsen PC, Bangma C, Carroll PR, Carter HB, Cooperberg MR, et al. Active Surveillance for Prostate Cancer: A Systematic Review of the Literature. Eur Urol 2012:1–8.
- Sundi D, Ross AE, Humphreys EB, Han M, Partin AW, Carter HB, 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.
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- Sundi D, Kryvenko ON, Carter HB, Ross AE, Epstein JI, Schaeffer EM. 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;191:60–7.
- Pietzak EJ, Van Arsdalen K, Patel K, Malkowicz SB, Wein AJ, Guzzo TJ. Impact of Race on Selecting Appropriate Patients for Active Surveillance With Seemingly Low-risk Prostate Cancer. Urology 2015;85:436–41.
- Mahal BA, Aizer A a, Ziehr DR, Hyatt AS, Choueiri TK, Hu JC, et al. Racial Disparities in Prostate Cancer-Specific Mortality in Men With Low-Risk Prostate Cancer. Clin Genitourin Cancer 2014:1–7.
- Sundi D, Faisal FA, Trock BJ, Landis P, Feng Z, Ross AE, et al. Reclassification rates are higher among African American men than Caucasians on active surveillance. Submitt Manuscr 2014.
- 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.
- Abern MR, Bassett MR, Tsivian M, Bañez LL, Polascik TJ, Ferrandino MN, 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.
Debasish Sundi, MD and Edward M. Schaeffer, 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.
James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD