METHODS: A literature review through the Medline database published from 1990 until August 2015 was performed to identify studies reporting outcomes of the AA population with low-risk PCa that underwent either AS or treatment. An additional search for studies on genetic mechanisms involved in development of PCa in AA men was also performed.
FREE DAILY AND WEEKLY NEWSLETTERS OFFERED BY CONTENT OF INTEREST
Did you find this article relevant? Subscribe to UroToday-GUOncToday!
The fields of GU Oncology and Urology are advancing rapidly including new treatments, enrolling clinical trials, screening and surveillance recommendations along with updated guidelines. Join us as one of our subscribers who rely on UroToday as their must-read source for the latest news and data on drugs. Sign up today for blogs, video conversations, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.
CONCLUSIONS: AA men with clinically defined low-risk PCa may have either a higher grade or volume of cancer that was not detected on routine evaluation. Therefore, AS among such patients should be approached with caution. We recommend discussing such risks with AA patients with an acknowledgement that existing favorable outcomes noted in largely Caucasian populations may not be applicable to AA patients. We propose a modified evaluation plan for AA patients that includes an early confirmatory biopsy preceded by an magnetic resonance imaging to optimally detect occult cancer foci.
Prostate Cancer and Prostatic Diseases (2017) 20, 127–136; doi:10.1038/pcan.2016.56; published online 18 April 2017
Prostate cancer (PCa) is the second most incident cancer and the fifth leading cause of cancer death among men worldwide. In the era of widespread screening with PSA, PCa incidence has increased markedly over time, particularly among men with low-risk PCa defined as clinical stage T1-T2a, serum level PSA level <10 ng ml− 1 and Gleason score (GS) ⩽ 6 by the National Comprehensive Cancer Network (NCCN) guidelines panel.¹ Previously Epstein et al. derived PCa criteria associated with pathologically ‘insignificant tumors’ (volume ⩽0.5 cm and Gleason sum ⩽ 6) that would pose little threat to an individual’s life and would potentially be better off if untreated. These pretreatment criteria were clinical stage T1c, Gleason sum ⩽6, PSAo10 ng ml− 1, PSA density (PSAD) ⩽0.15 ng ml− 1 gm− 1, ⩽2 positive biopsy cores and ⩽ 50% cancer involvement per core.2 These latter criteria make up the NCCN very-low-risk group. Patients presenting with features suggestive of either low or very-low risk PCa often represent a dilemma for patients and physicians when weighing the options of treatment versus surveillance. Concerns about surveillance are related to the potential for upgrading or staging based upon (1) the lack of precision of our current clinical staging modalities; (2) proven follow-up strategies; and (3) the need for future testing including imaging and subsequent biopsies, which can induce morbidity and the psychological distress of having PCa that is not treated. Treatment concerns are appropriate based on significant morbidity and functional impairment (urinary incontinence and erectile dysfunction, for example) associated with definitive treatment for PCa.3,4 Fortunately, for many appropriately selected men with low-risk PCas, active surveillance (AS) is an excellent management option that avoids treatment of many men whose cancer does not progress and defers treatment until the time of proven progression in the subset of men in whom treatment is truly required.5
The oncologic outcomes of AS for men with very-low-risk PCa are overall excellent. In a recent report of results from a large AS cohort, 36% of patients demonstrated disease reclassification at a median of 2 (range: 0.3–16) years, the cumulative incidence of treatment was 57% after a median follow-up of 15 years, and only 2 out of 1298 (0.15%) men died of PCa.6
As patients’ and physicians’ awareness of AS as a viable management option for well-selected men has increased, the use of AS has increased over time.7 However, while the oncological outcomes of AS are quite favorable, these outcomes are based largely on white patient cohorts, as African American (AA) men are under-represented consisting of 7–10% of subjects in AS series reported to date.6,8
The under-representation of AA in reported AS outcomes is particularly important because of the unique epidemiology of PCa in AA men whereby the age-adjusted PCa incidence and mortality rates are ~ 60% and twofold higher (respectively) when comparing AA and Caucasian men.9,10
In this review, we summarize the outcomes of AA patients who would have been eligible for AS or were actually enrolled in AS programs by virtue of exhibiting clinically defined low-, very-low risk PCa. We also describe emerging evidence regarding differences in the pathology and biology of PCa among AA and white men that could better inform future decisions related to AS. Finally, we suggest clinical strategies based upon available data that may help to further stratify AA men presenting with low-risk PCa for AS, watchful waiting or active treatment.
We conducted a review of the literature through the Medline (PubMed) database published from 1990 until August 2015 using the terms ‘active surveillance,’ ‘African American’, ‘black,’ ‘racial disparity,’ ‘watchful waiting,’ ‘prostate cancer’, ‘survival’, ‘epigenetic mechanisms’ and ‘chromosomal alterations’. Combinations of these terms were used to identify the relevant articles. From these resources, we identified all relevant studies using various combinations of the text terms. Only articles in the English language were included. All of the retrospective cohort studies, prospective case series and randomized controlled trials were accepted as relevant. The first search resulted in 585 articles and after review of the abstracts, the full-text of articles was read. Reference lists of all relevant articles were also reviewed to define additional articles related to the subject matter. Finally, 43 articles were selected that provided the most relevant data for the review.
Outcomes based on pathological results of AA men who would have qualified for AS but underwent radical prostatectomy. The characteristics and results of studies on pathologic results of AA men who would have qualified for AS are summarized in Tables 1 and 2. Resnick et al. compared the post-radical prostatectomy data of AA and white PCa patients that were in the low-risk group. The low-risk criteria were PSA ⩽10, clinical stage ⩽T1c, GS⩽6 and positive cores ⩽2 and 354 white and 53 AA patients met these criteria. The authors found no significant differences in outcomes after surgery (pathologic stage, upgrading, and recurrence) between the two races.19 A key limitation of this study was small sample size and associated likelihood of type II error.
Ha et al. compared the rates of upstaging and upgrading after radical prostatectomy (RP) between AA and white men with low-risk PCa who would have qualified for AS but underwent immediate radical prostatectomy. The authors determined eligibility or AS according to modified NCCN low-risk PCa criteria (clinical stage ⩽T2a, Gleason sum ⩽ 6 and PSA <10 ng ml− 1 for men with life expectancy <10 years with additional criteria for men with life expectancy 10–20 years: ⩽2 positive biopsy cores and ⩽50% cancer involvement per core). Comparing 124 AA and 148 white patients. Disease upstaging (defined as ⩾ pT3a) was observed in the 19.4% of AA and 10.1% of white patients (univariate P = 0.037).11 The authors concluded that AS in AA men with PCa carries a higher risk of advanced stage cancer compared to the whites and more stringent AS entrance criteria may be necessary for AA men. While interesting, this study was limited by several factors, including explanation of how life expectancy was determined, lack of central pathological review, unknown relative contribution of study subjects from each of the contributing institutions, and missing multivariable analyses for the primary study end point (upstaging).
Sundi et al. reported on a cohort of 256 AA and 1473 white men from Johns Hopkins who met NCCN very-low-risk criteria but underwent immediate radical prostatectomy rather than AS. AA men were found to more frequently harbor adverse pathological features at surgery. In particular, AA men were more likely to experience pathological upgrading from Gleason sum ⩽6 at biopsy to Gleason sum ⩾7 at prostatectomy (27.3 vs 14.4%; P<0.001) and positive surgical margins (9.8 vs 5.9%; P = 0.02). The authors also performed multivariable analysis, and AA race was detected as an independent predictor of adverse pathological features (odds ratio (OR): 3.23; P = 0.03), pathological upgrading (OR: 2.26; P = 0.03) and higher pathological risk score Cancer of the Prostate Risk Assessment Post-surgical Score (CAPRA-S) ⩾ 3; 21.0 vs 5.7%; P<0.001. The main limitations of this study were its retrospective design and single-center analysis.12
The same group subsequently published results of a detailed pathological analysis of a randomly picked subset of their institutional surgical very-low-risk cohort. Including 87 AA and 89 white men, the authors reported characteristics of the dominant tumor nodule in each prostatectomy specimen, defined as the largest tumor nodule with the highest Gleason sum, and found that compared to white men, dominant nodules in AA men were larger (median 0.28 vs 0.13 cm3, P = 0.002) and more often located in the anterior aspect of the prostate (51 vs 29%, P = 0.003). This is notable because standard prostate biopsy uses a posterior approach and may therefore miss significant cancer foci in AA men, which may partly explain earlier reported disparities in pathological and oncologic outcomes. As a result, the authors also suggested that either imaging (such as with multi-parametric prostate magnetic resonance imaging) or biopsy sampling of anterior zone is potentially critical to to detect significant anterior tumors, especially when AS is being considered.13
In another study PSA levels and three-dimensional (D) tumor volumes of AA and white radical prostatectomy patients that have the same health care setting were compared and AA men were found to have significantly higher pretreatment PSA and 3D tumor volume.22 Similarly PCa volume and GS of AA patients that underwent radical prostatectomy was compared with the group of white males matched for age, clinical stage, serum PSA level, year of surgery, prostate weight, and prostate biopsy strategy. The groups were found to be similar for biopsy results but the results of radical prostatectomy specimens revealed higher prostatectomy GS and higher mean tumor volume in the AA population.23
Faisal et al. evaluated a cohort of 15 993 white and 1634 AA patients from Johns Hopkins (inclusive of all NCCN risk strata) who underwent radical prostatectomy, and for whom long-term followup data were available. The AA men presented with younger age at time of diagnosis, higher preoperative PSA values, and higher preoperative PSAD compared with the white patients. AA men were more likely to be upgraded at RP both in the very-low-risk PCa (29.3 vs 15.4%; P<0.001) and low-risk PCa (30.8 vs 24.9%; P = 0.001) groups. Positive surgical margin rates were also found to be higher in AA men with the very-low-risk (10.5 vs 5.8%; P = 0.006), low-risk (14.0 vs 10.5%; P = 0.008) categories. In addition in multivariate analysis, AA race was found to be an independent predictor of biochemical recurrence in the preoperative model of NCCN low-risk group (hazards ratio (HR): 2.16, 95% confidence interval (CI): 1.53–3.04, P<0.0001). Most notably, The authors concluded that racial disparities in pathological and oncological outcomes are most pronounced in NCCN very-low-, low- and intermediate-risk groups, and that AA men with very-low-to low-risk PCa should be counseled regarding their elevated risk for adverse outcomes when deciding among management options.14
Vora et al., reporting on a cohort of low-risk patients (604 white men and 355 AA men) who underwent radical prostatectomy at Georgetown University Hospital and Washington Hospital Center. AA men experienced pathologic upgrading more frequently than white men in this cohort (37% vs 26%, P<0.001). The authors found that AA race was independently associated with pathologic upgrading after controlling for age, body mass index, PSA, prostate volume, and biopsy metrics of cancer volume (adjusted OR: 1.736, 95% CI: 1.309–2.301, P = 0.01).15
Recently published SEER database results compared PCa-specific mortality results of low-risk AA and white populations. The cohort consisted of 51 315 patients of whom 7523 were AAs. Results of the study revealed that AA population was less likely to undergo curative treatment than white patients (adjusted OR, 0.93; 95% CI: 0.87–0.98; P = 0.011). Furthermore, within the group of patients that underwent curative treatment, AA patients were significantly less likely to receive prostatectomy (adjusted OR, 0.40; 95% CI, 0.34–0.47; P<0.001). PCa-specific mortality rates were found to be higher in the AA population compared with white population, with 5-year PCa-specific mortality rates of 1.0 vs 0.64% (P = 0.019). Also AA race was detected as an independent risk factor for PCa-specific mortality (HR: 1.45 (1.03–2.05), P = 0.032). When the results of patients who underwent curative intent were considered, again AA population was found to have higher mortality rates and AA race was detected as an independent risk factor for PCa-specific mortality.16
In another recent study, results of patients underwent radical prostatectomy with low-grade PCa (classified as either low- o intermediate-risk) were investigated. There were 298 AA and 1673 white patients in the study population, and the inclusion criteria were as follows: biopsy GS⩽7 (3+4), T-stage ⩽ T2c, PSA ⩽20 ng ml− 1. All patients underwent radical prostatectomy and after radical prostatectomy, AA men were found to have higher rates of pathological GS⩾ 7 (52% vs 43%; P = 0.01) and seminal vesicle invasion (6% vs 3%; P = 0.02). AA patients were found to have worse 7-year biochemical recurrence-free survival rates compared to the white patients (86% vs 79%, respectively (P = 0.035). However AA race was not found to be an independent risk factor for biochemical recurrence after adjusting for serum PSA, T stage, extraprostatic extension, seminal vesicle invasion, positive surgical margins and pathological GS (HR: 1.38, 95% CI: 0.92–2.07 P = 0.12).17
Weiner et al. investigated the results of low-risk PCa patients (low risk defined as GS: 6, PSA<10 ng ml− 1, and cT1–T2) from national cancer database. The primary objective of the study was to evaluate the effect of delayed radical prostatectomy on adverse pathological outcomes defined as pathologic upgrading, upstaging, nodal metastases and positive surgical margins. Together with time from biopsy to RP412 months, AA race was shown to increase the risk of adverse pathological outcomes (OR: 1.16, 95% CI: 1.05–1.28, P = 0.004).18
There are also studies concluding no significant differences between the AA and white populations. Truong et al. developed and validated a nomogram to determine the risk of GS upgrading among men with Gleason sum ⩽ 6 on biopsy. Race was not found to be a predictor of GS upgrading in the univariate analysis, although there were only 13 AA men in the analyzed cohort (3.1%).24
GS upgrading and its effect on pathological outcomes was investigated in the study from Shared Equal Access Regional Cancer Hospital (SEARCH) Database. There were 1113 patients and 347 (31%) of them were AA. In the multivariate analysis, AA race was not found to be a predictor of GS upgrading.25 In the same database, outcomes of low-risk (defined as PSAAA and 145 AA) but underwent radical prostatectomy instead showed that race was not associated with biochemical recurrence. However, the authors investigated the effect of race after re-defining low-risk criteria in a population of age <60, not obese, and no Agent Orange exposure and found that AA race was associated with biochemical progression (log-rank, P = 0.003).26 Recently, an update from the SEARCH database was published. In this study, 355 AA and 540 Caucasian men with clinical low-risk Pca defined as Gleason 3+3, ⩽cT2a, PSA⩽10 ng ml− 1 treated with radical prostatectomy were evaluated. AA race was not found to be associated with pathological upgrade (OR 1.33, 95% CI 0.92-1.93, P = 0.12), upstaging (OR 1.09, 95% CI 0.65–1.83, P = 0.73), or positive surgical margins (OR 1.04, 95% CI 0.73–1.49, P = 0.81). The 5-year recurrence-free survival rates were also similar for the AA and Caucasian populations (Log-rank P = 0.178).27 Thus these data support that among this cohort of men evaluated and managed in an equal access setting that ethnicity was no longer relevant to adverse pathologic and biochemical recurrence outcomes.
Jalloh et al. reported on a cohort of low-risk PCa patients treated with radical prostatectomy at either University of California San Francisco or members of the CaPSURE registry.28 In this cohort, there were 273 AA men and 3771 white men (89.1%); and among this cohort, there were 83 AA and 1177 white men who met NCCN very-low-risk criteria. Considering all low-risk men, AA were shown to have a higher rate of positive surgical margins (31 vs 21%, P<0.01), though no other differences in pathological outcomes were shown, including sub-analyses of the very-low-risk cohort. An important drawback of this study was the lack of central pathological review considering that the data come from many centers.20
Schreiber et al. recently published data on 1794 patient (229 AA) that underwent radical prostatectomy utilizing the SEE database with inclusion criteria of PSA <10 ng ml− 1, GS:6, diagnostic biopsy with at least 12 cores with ⩽2 positive cores They compared the AA and white populations with regard to pathologic upstaging to more aggressive disease or GS upgrading to higher-risk disease without central pathological review. There were no statistically significant differences between the two populations with regard related to to the pathological GS (P = 0.99), pathologic extent of disease (P = 0.34), margins (P = 0.43), CAPRA-S score (P = 0.56), or adverse features (P = 0.45). In addition, AA race was not predictive for adverse pathological features on univariate (OR, 1.19; 95% CI, 0.75–1.88; P = 0 .45) or multivariable analysis (OR, 1.43; 95% CI, 0.87–2.33; P = 0.16).21
Overall at least seven published studies provide evidence for a higher likelihood of adverse pathological factors with respect to GS, volume of disease, or positive surgical margins among AA men with apparent low-risk PCa who actually underwent RP when compared with a similar Caucasian cohort. Four other comparative studies (three published) found no such differences. Differences in the study outcomes may be related to either (1) relatively smaller numbers of AA patients when compared to the Caucasian cohort that they were compared with or (2) accrual from multi-institutional cohorts where there was no central review of pathology or (3) cohorts studied in equal access settings.
Results of prospective studies of AS including AA Men
There are relatively few studies investigating the results of AS in AA men. These studies have different inclusion criteria for AS and also different follow-up strategies and different end points. The characteristics and results of prospective studies on AS involving the AA population are summarized in Tables 3 and 4.
Iremashvilli et al, reported on the results of the 272 men (24 of them were AA) who had enrolled into AS at the University of Miami. The criteria for AS were clinical stage ⩽T2a, Gleason sum ⩽6, positive cores ⩽ 2, and cancer involvement per core ⩽20%. The primary study end point was disease progression defined as high-grade cancer, more than two positive cores or greater than 20% involvement of any core on surveillance biopsy. The authors found out that AA patients are more likely to experience disease progression on surveillance and that AA race was an independent predictor of progression on surveillance after controlling for number of positive biopsy cores, prostate volume, and PSAD.8
Abern et al. studied patients on AS from the Duke Prostate Center, including patients with the following inclusion criteria: PSA <10 ng ml− 1; GS⩽ 6; and ⩽ 33% of cores with cancer on diagnostic biopsy. The primary outcome was discontinuation of AS for treatment due to PC progression. Totally there were 145 patients (105 (72%) white, 32 (22%) AA and 8 (6%) other race). The authors found that, AA race was the sole predictor of discontinuation of AS (HR: 3.08, P = 0.01), after adjusting for socioeconomic and clinical parameters at the time of PCa diagnosis. Details of disease reclassification were not reported, and overall disease reclassification rates between race groups were similar (37 vs 18%, P = 0.15).29
Sundi et al. reported on an AS cohort of NCCN very-low-risk patients from Johns Hopkins. They studied 615 white and 39 AA patients, using a competing-risks analysis to determine race-specific hazards of progression on serial biopsy. Progression was defined as detection of ⩾ 3 positive cores or ⩾50% percentage core involvement (volume criteria) or detection of Gleason sum ⩾7 (grade criteria). On multivariable analysis, AA men were 1.8-fold more likely to experience disease progression on serial biopsy (sHR 1.80, P = 0.003). The main driver of this disparity was progression by upgrading: AA men were 3.02-fold more likely to likely demonstrate high-grade cancer on serial biopsy (adjusted P = 0.002).31
Odom et al. reported the results of patients from 3 centers (Cleveland Clinic, Detroit Medical Center, and Centre Hospitalier Universitaire in Guadeloupe). They compared the results of 67 AA and 72 white patients who underwent AS. After a median followup of 34 months, AA were more likely to experience disease progression (OR: 4.6; 95% CI, 1.03–5.08; P = 0.04) and receive treatment (OR: 2.4; 95% CI, 1.1–5.2; P = 0.03).30
Davis et al. recently described the University of Texas, MD Anderson Cancer Center AS experience. The authors defined a favorable risk group, characterized by having a biopsy of ⩾ 10 cores showing either a 3 + 3 GS in one core (tumor focus <3 mm) or 3 + 4 GS in one core (tumor focus<2 mm) and PSA level below 4 ngml − 1. Among 191 favorable risk patients, reclassification occurred in two out of the 17 AA and 24 out of the 155 white men and risk of disease reclassification was found to be similar (univariate HR: 1.97 (95% CI: 0.27–14.65), P = 0.51).32 Of note, 86.4% of the patients in this series had a confirmatory biopsy before being enrolled into the AS cohort.
All of the studies discussed above are limited in that they utilized single-institution retrospective approaches with relatively small sample sizes. Can the advisability of AS for AA men be informed by any existing prospective data? Some might argue that the Prostate Cancer Intervention versus Observation Trial (PIVOT) offers a potentially important insight, even though the trial did not expressly study AS, (that is, distinct from observation). In a Veterans’ Affairs system-wide cohort, patients were included according to age <75 years, PSA level <50 ng ml− 1, and any GS. Of recruited patients, 32% were AA. In the subgroup analysis of the AA population radical prostatectomy (as compared to observation) was shown to have no significant benefit on overall survival rate, disease-specific survival rate, or bone metastases. If ‘observation’ and ‘AS’ are considered similar in that both avoid immediate curative treatment, does the absence of an effect between trial arms argue for the safety of AS regardless of risk? At face value, some might argue the affirmative position. However, several points should be examined further. First, after central pathological review, 48% of the patients were found to have GS: 7 or higher and 66% of the patients had tumors in the intermediate or high-risk categories, thus substantially limiting the generalizability of PIVOT to AS cohorts. Further limiting generalizability, the Veterans’ Affairs patient cohort is potentially unique in terms of provider or patient characteristics. Most critically, PIVOT did not report oncologic outcomes for patients who would meet major AS criteria; therefore its applicability to AS is highly limited.33 However given the high mortality among PIVOT trial participants (that is, approximately 48%) with no difference in mortality between those undergoing observation versus prostatectomy the data do provide evidence to support limiting aggressive therapy among men with significant comorbidities. 32
DISPARITIES IN TUMOR BIOLOGY AND GENETICS
To uncover the potential biologic basis of observed clinical features of PCa among men of various racial groups, an emerging body of literature has examined race-based molecular and genomic profiles of PCas. Epigenetic DNA alterations, chromosomal alterations, and gene expression profile alterations have been identified as factors associated with racial disparities.34–42
Promoter methylation, as a mechanism of epigenetic DNA alteration, commonly results in reduced gene expression and this phenomenon is commonly observed in PCa, and has been described as a regulator of GSTP1, PTEN, CD44 and E-cadherin genes.34–36 Chromosomal alterations leading to mutations that result in loss or gain of function of cancer related genes are important in the development of PCa. Several groups have determined that chromosomal copy number variation does indeed exist between PCas of AA and white men.37–39 For instance Castro et al. showed that the frequency of chromosomal alterations among an AA cohort of men with localized PCa was similar to a cohort of Caucasian men with metastatic PCa.37 Gene expression profile alterations such as differential expression of PCGEM1,40 ERG, AMACR, SPINK1, NKX3-1, GOLM141 and altered expression of metastasis related genes like autocrine mobility factor receptor, chemokine (C-X-C motif) receptor 4, and matrix metalloproteinase 942 have been shown. The extent to which these findings are associated with the progression of PCa and the optimal selection of patients (especially AA men) for AS is critical and requires further study.
Figure 1. Suggestions related to the selection of candidates for AS, imaging, and follow-up strategies in AA population. AA, African American; AS, active surveillance; DRE, digital rectal exam; GS, Gleason score; MRI, magnetic resonance imaging; PIVOT, Prostate Cancer Intervention versus Observation Trial.
In the clinical setting, decision making processes related to AS, including patient selection, relevant testing to be done, follow-up of patients during AS, and the decision to proceed with active treatment depend on many factors. The flow chart proposed in Figure 1 is an attempt to utilize existing information to optimize the selection of AA patients for AS. A patient’s age, comorbid conditions and life expectancy should be taken in to account as the first step. In the PIVOT trial, 47 and 49.9% of the men died after a median follow-up of 10 years in the radical prostatectomy and observation arms, respectively.33 A confirmatory biopsy has the potential to mediate better patient assignment for AS and therefore follow-p periods may be delayed from 3 to 6 months.32 AA men were shown to have tumors located anteriorly more often than Caucasian men.13 Therefore, use of multi-parametric magnetic resonance imaging and guided biopsies during initial selection and follow-up may also better identify patients with more disease than otherwise apparent especially in the AA population.
In summary, the current studies suggest that AA men with very low or low-risk clinical features often have clinically significant PCa when subjected to radical prostatectomy. Biologic heterogeneity of Pca has been shown in a number of recent studies at the DNA, RNA and protein level in comparative studies between AA and Caucasian men. Further studies of such molecular alterations is urgently needed to determine the mechanisms underlying aggressive PCa in both AA and Caucasian men. There is a lack of robust data on AS among AA men and this together with adverse features noted in several studies of AA men who underwent prostatectomy raises concerns about its adoption in this population. We believe that the data support counseling AA with very low/low-risk PCa features about the possibility of occult more aggressive disease being present. Further AA men should be aware that the favorable results of AS studies to date have largely been carried out among Caucasian cohorts. However, based on the promise of avoiding over treatment of AA men we advocate the cautious use of AS among AA men at this time with several suggestions related to the selection of candidates imaging and follow-up strategies (see Figure 1). Recently The American Society of Clinical Oncology recommended AS as a management strategy for most men with localized low risk but included AA men within a group of patients in whom close scrutiny should be used whic also included men with high volume GS 6 cancer and those younger than age 55. Larger prospective studies with longer follow-up of AA men on AS are needed that incorporate banking of tissue for molecular studies, and novel imaging strategies. Such an effort will eventually provide a wealth of information for the optimal selection of candidates for AS.
Read More: Commentary from the Associate Editor of PCAN
2. Epstein JI, Walsh PC, Carmichael M, Brendler CB. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 1994; 271: 368–374.
3. Alemozaffar M, Regan MM, Cooperberg MR, Wei JT, Michalski JM, Sandler H et al. Prediction of erectile function following treatment for prostate cancer. JAMA 2011; 306: 1205–1214.
4. Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. Engl J Med 2008; 358: 1250–1261.
5. 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; 62: 976–983.
6. Tosoian JJ, Mamawala M, Epstein JI, Landis P, Wolf S, Trock BJ et al. Intermediat and longer-term outcomes from a prospective active-surveillance program fo favorable-risk prostate cancer. J Clin Oncol 2015; 33: 3379–3385.
7. Cooperberg MR, Carroll PR. Trends in management for patients with localize prostate cancer, 1990-2013. JAMA 2015; 314: 80–82.
8. 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: 1594–1599.
9. 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: 985–997.
10. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65: 5–29.
11. Ha YS, Salmasi A, Karellas M, Singer EA, Kim JH, Han M et al. Increased incidence of pathologically nonorgan confined prostate cancer in African-American men eligible for active surveillance. Urology 2013; 81: 831–835.
12. 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: 2991–2997.
13. Sundi D, Kryvenko ON, Carter HB, Ross AE, Epstein JI, Schaeffer EM. 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.
14. Faisal FA, Sundi D, Cooper JL, Humphreys EB, Partin AW, Han M et al. Racial disparities in oncologic outcomes after radical prostatectomy: long-term follow-up. Urology 2014; 84: 1434–1441.
15. Vora A, Large T, Aronica J, Haynes S, Harbin A, Marchalik D et al. Predictors of Gleason score upgrading in a large African-American population. Int Urol Nephrol 2013; 45: 1257–1262.
16. Mahal BA, Aizer AA, 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; 12: e189–e195.
17. Yamoah K, Deville C, Vapiwala N, Spangler E, Zeigler-Johnson CM, Malkowicz B et al. African American men with low-grade prostate cancer have increased disease recurrence after prostatectomy compared with Caucasian men. Urol Oncol 2015; 33: 70 e15–22.
18. Weiner AB, Patel SG, Eggener SE. Pathologic outcomes for low-risk prostate cancer after delayed radical prostatectomy in the United States. Urol Oncol 2015; 33: 164 e111–164 e167.
19. Resnick MJ, Canter DJ, Guzzo TJ, Brucker BM, Bergey M, Sonnad SS et al. Does race affect postoperative outcomes in patients with low-risk prostate cancer who undergo radical prostatectomy? Urology 2009; 73: 620–623.
20. Jalloh M, Myers F, Cowan JE, Carroll PR, Cooperberg MR. Racial variation in prostate cancer upgrading and upstaging among men with low-risk clinical characteristics. Eur Urol 2015; 67: 451–457.
21. Schreiber D, Chhabra A, Rineer J, Weedon J, Schwartz D. A population-based study of men with low-volume low-risk prostate cancer: does African-American race predict for more aggressive disease? Clin Genitourin Cancer 2015; 13: e259–e264.
22. Moul JW, Connelly RR, Mooneyhan RM, Zhang W, Sesterhenn IA, Mostofi FK et al. Racial differences in tumor volume and prostate specific antigen among radical prostatectomy patients. J Urol 1999; 162: 394–397.
23. Sanchez-Ortiz RF, Troncoso P, Babaian RJ, Lloreta J, Johnston DA, Pettaway CA. African-American men with nonpalpable prostate cancer exhibit greater tumor volume than matched white men. Cancer 2006; 107: 75–82.
24. Truong M, Slezak JA, Lin CP, Iremashvili V, Sado M, Razmaria AA et al. Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer. Cancer 2013; 119: 3992–4002.
25. Freedland SJ, Kane CJ, Amling CL, Aronson WJ, Terris MK, Presti JC Jr. et al. Upgrading and downgrading of prostate needle biopsy specimens: risk factors and clinical implications. Urology 2007; 69: 495–499.
27. Leapman MS, Freedland SJ, Aronson WJ, Kane CJ, Terris MK, Walker K 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.
28. Lubeck DP, Litwin MS, Henning JM, Stier DM, Mazonson P, Fisk R et al. The CaPSURE database: a methodology for clinical practice and research in prostate cancer. CaPSURE Research Panel. Cancer of the Prostate Strategic Urologic Research Endeavor. Urology 1996; 48: 773–777.
29. Abern MR, Bassett MR, Tsivian M, Banez 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.
30. Odom BD, Mir MC, Hughes S, Senechal C, Santy A, Eyraud R et al. Active surveillance for low-risk prostate cancer in African American men: a multiinstitutional experience. Urology 2014; 83: 364–368.
31. Sundi D, Faisal FA, Trock BJ, Landis PK, Feng Z, Ross AE et al. Reclassification rates are higher among African American men than Caucasians on active surveillance. Urology 2015; 85: 155–160.
32. Davis JW, Ward JF 3rd, Pettaway CA, Wang X, Kuban D, Frank SJ et al. Disease reclassification risk with stringent criteria and frequent monitoring in men with favourable-risk prostate cancer undergoing active surveillance. BJU Int 2015; 118: 68–76.
33. Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012; 367: 203–213.
34. Nelson WG, De Marzo AM, Yegnasubramanian S. Epigenetic alterations in human prostate cancers. Endocrinology 2009; 150: 3991–4002.
35. Woodson K, Hayes R, Wideroff L, Villaruz L, Tangrea J. Hypermethylation of GSTP1,
CD44, and E-cadherin genes in prostate cancer among US Blacks and Whites. Prostate 2003; 55: 199–205.
36. Woodson K, Hanson J, Tangrea J. A survey of gene-specific methylation in human prostate cancer among black and white men. Cancer Lett 2004; 205: 181–188.
37. Castro P, Creighton CJ, Ozen M, Berel D, Mims MP, Ittmann M. Genomic profiling of prostate cancers from African American men. Neoplasia 2009; 11: 305–312.
38. Cher ML, Lewis PE, Banerjee M, Hurley PM, Sakr W, Grignon DJ et al. A similar pattern of chromosomal alterations in prostate cancers from African-Americans and Caucasian Americans. Clin Cancer Res 1998; 4: 1273–1278.
39. Rose AE, Satagopan JM, Oddoux C, Zhou Q, Xu R, Olshen AB et al. Copy number and gene expression differences between African American and Caucasian American prostate cancer. J Transl Med 2010; 8: 70.
40. Petrovics G, Zhang W, Makarem M, Street JP, Connelly R, Sun L et al. Elevated expression of PCGEM1, a prostate-specific gene with cell growth-promoting function, is associated with high-risk prostate cancer patients. Oncogene 2004; 23: 605–611.
41. Yamoah K, Johnson MH, Choeurng V, Faisal FA, Yousefi K, Haddad Z et al. Novel biomarker signature that may predict aggressive disease in African American men with prostate cancer. J Clin Oncol 2015; 33: 2789–2796.
42. Wallace TA, Prueitt RL, Yi M, Howe TM, Gillespie JW, Yfantis HG et al. Tumor immunobiological differences in prostate cancer between African-American and European-American men. Cancer Res 2008; 68: 927–936.
MI Gökce1,2, D Sundi1, E Schaeffer3 and C Pettaway1
1Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;
2Department of Urology, Ankara University School of Medicine, Ankara, Turkey and