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Patient Characteristics at Prostate Cancer Diagnosis in Different Races at an Academic Center Serving a Diverse Population
Accepted Manuscript Patient Characteristics at Time of Prostate Cancer Diagnosis in Different Races at an Academic Center Serving a Diverse Population Tejas Suresh, M.D., Janaki Sharma, M.D., Sanjay Goel, M.D., Evan Kovac, M.D., Qi Gao, Ph.D, Benjamin Gartrell, M.D. PII:
S1558-7673(18)30592-5
DOI:
https://doi.org/10.1016/j.clgc.2018.12.003
Reference:
CLGC 1182
To appear in:
Clinical Genitourinary Cancer
Received Date: 9 August 2018 Revised Date:
30 November 2018
Accepted Date: 1 December 2018
Please cite this article as: Suresh T, Sharma J, Goel S, Kovac E, Gao Q, Gartrell B, Patient Characteristics at Time of Prostate Cancer Diagnosis in Different Races at an Academic Center Serving a Diverse Population, Clinical Genitourinary Cancer (2019), doi: https://doi.org/10.1016/ j.clgc.2018.12.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Patient Characteristics at Time of Prostate Cancer Diagnosis in Different Races at an Academic Center Serving a Diverse Population Tejas Suresh M.D., 4Janaki Sharma M.D., 4Sanjay Goel M.D., 3Evan Kovac M.D., 2Qi Gao Ph.D, Benjamin Gartrell M.D. 1 Departments of Medicine, 2Epidemiology, 3Urology and 4Medical Oncology; Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA 1
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Corresponding Author Tejas Suresh M.D. Yale University School of Medicine 333 Cedar Street Room WWW 209 New Haven, CT 06520 Phone: 475 – 224 - 0734
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Clinical Practice Points
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In the United States, prostate cancer (PCa) incidence and death rate is greater in non-Hispanic Blacks (NHB) than non-Hispanic Whites (NHW), and slightly lower in Hispanic (H) than NHW. In our study of a large urban academic tertiary care center, men of different racial groups have significant differences at the time of presentation of newly diagnosed PCa. African-American and Hispanic men tend to have disease at earlier ages, lower SES, higher Gleason scores and higher numbers of patients with metastatic disease at presentation. Our data is novel in that we show that Hispanic men also present with aggressive disease, and along with AA, are likely at risk for inferior outcomes. This may impact thought on race/ethnicity-specific screening recommendations.
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Abstract Background:
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In the United States, prostate cancer (PCa) incidence and death rate is greater in non-Hispanic Blacks (NHB) than non-Hispanic Whites (NHW), and slightly lower in Hispanic (H) than NHW. We sought to compare the sociodemographic and baseline prognostic factors at the time of PCa diagnosis in different races/ethnicities at a large, academic center serving an ethnically diverse population.
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Methods:
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The Montefiore Medical Center (MMC) Cancer Registry was used to generate a comprehensive list of all patients with PCa diagnosed from the years 2004 to 2014. Clinical Looking Glass (a proprietary searchable database of patient information) and individual patient chart review was used to obtain data including age at diagnosis, socioeconomic status (SES), clinical Gleason score, clinical stage and PSA at diagnosis. Patients were classified by self-identified race/ethnicity as H, NHB, NHW or other(O). Chi-square test was used for categorical variables, while ANOVA or Kruskal-Wallis test was used for continuous variables. All analysis was performed using SAS 9.3 (Cary, NC). Results:
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We identified 2352 patients with newly diagnosed PCa during the study period: 778 (H), 1046 (NHB), 486 (NHW) and 42 (O). NHW men were significantly older at diagnosis (H 63.2, NHB 63.4, NHW 67, O 63.0, p < 0.0001). Mean SES for H and NHB men were significantly lower (SES below the average: H 92.8%, NHB 91.3%, NHW 56.6%, O 75%, p<0.0001). Gleason score at diagnosis differed between these race groups (Gleason ≤6 PCa: H 42.8%, NHB 39.1%, NHW 52.2%, O 50%; Gleason 8-10: H 15.8%, NHB 17.6%, NHW 14.3%, O 16.7%, p=0.0005). The proportion of men with metastatic disease at diagnosis also differed significantly between groups (H 7.5%, NHB 9.0%, NHW 4.3%, O 9.5%, p=0.0139). Using pairwise comparison, the odds ratio for higher Gleason score at presentation between NHB vs NHW was 1.592 (p <0.001), and was 1.378 for H vs NHW (p = 0.0200). Pairwise comparison for metastatic disease at diagnosis showed an odds ratio of 2.186 for NHB vs NHW (p = 0.0087). After adjusting for SES, the odds ratio for higher Gleason score comparing NHB vs NHW is 1.55 (p=0.001). Although the odds of metastatic disease were higher in H compared to NHW (OR=1.784), they were not statistically different (p = 0.1197). Conclusions: At our center, the clinical features of men from different racial groups differ significantly at the time of newly diagnosed prostate cancer. Differences include age at diagnosis, SES, Gleason score and proportion with metastatic disease. Our pairwise comparisons between different
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ethnic groups suggest that prostate cancer in Hispanic men may be more similar to NHB than to NHW patients and are generally more aggressive at the time of diagnosis.
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Introduction and Background
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Prostate cancer (PCa) is the most commonly diagnosed non-skin cancer in men in the United States, and it is estimated that 161,360 men were diagnosed in 2017 and 26,730 died of their disease.1 In general, cancer related mortality has declined over the last several decades, but the decline has been consistently greater in NHW versus H or NHB populations.2 In the United States, PCa incidence and death rate differ among races and ethnicities.1
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African-Americans (AA) have higher incidence1, earlier age at diagnoses3,4 and increased death rate1 from PCa. The incidence is 73% higher and the rate of death is 2.3-fold higher in AA men in the United States than in NHW men.1 According to one analysis of the Surveillance, Epidemiology, and End Results (SEER) Database from 2006-2012, 5% of black patients and 4% of white patients had distant disease at the time of diagnosis.1 Another analysis of SEER found that black patients were more likely to present with metastatic PCa compared to non-black patients in the years 2004-2011 with an adjusted odds ratio of 1.65; P<0.001).5 An analysis of SEER data from metropolitan Detroit found that the odds ratio for the incidence of distant PCa was 3-5x higher for black compared to non-black patients.6 In the same publication, black patients undergoing radical prostatectomy had greater tumor volumes compared to non-black patients between the ages of 40-69, but autopsy data showed that PCa incidence at autopsy was similar between black and non-black patients. This suggests an earlier transition to biologically aggressive PCa in AA patients. AA patients with clinical American Urological Association (AUA) very low risk and low risk PCa who would meet criteria for active surveillance but elect to undergo immediate radical prostatectomy are more likely to have adverse pathological upgrading/upstaging compared to other races.7 While socioeconomic factors and limitations in access to care likely contribute to PCa disparities among minority communities in the United States8, biological differences including differential expression of PCa associated genes and higher likelihood of “triple-negative” prostate cancer in AA men have also been reported.9,10 Unlike NHBs, Hispanic (H) men in the United States have a lower PCa incidence and death rate than NHWs.11 This lower cancer related mortality rate among H populations, despite inferior SES, has been reported across multiple tumor types and is known as the “Hispanic Paradox.”12 According to data from SEER from 2008-2012, distant disease was present at diagnosis in 6% of H and 4% of NHW.11 Recent data from the national cancer database indicates a higher incidence of metastatic PCa at diagnosis in H (6.2%) and NHB (5.9%) compared to NHW (3.6%) and an inverse relationship of socioeconomic status and the odds of presenting with metastatic disease.13 Additionally, a recent analysis of SWOG clinical trial participants of Hispanic ethnicity, suggests no difference in overall survival between H and NHW PCa patients when adjusted for multiple comparisons.14 Montefiore Medical Center (MMC) is a large tertiary care center serving a diverse, urban population composed primarily of minorities in the Bronx. We have established an institutional PCa database. Here we report the socioeconomic, demographic and baseline prognostic factors at the time of PCa diagnosis among different races and ethnicities at our institution.
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Patients and Methods Creation of Database
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PCa patients were identified through the MMC cancer registry. Information was collected on patients diagnosed at our center from 2004 to 2014. The Clinical Looking Glass (a proprietary searchable database of patient information) and individual patient chart review were used to obtain data including race, age at diagnosis, year of diagnosis, socioeconomic status (SES, associated with the census track in which the patient lives), clinical Gleason score, clinical T stage at diagnosis and PSA at diagnosis. SES combines information on patient income, housing value, education and occupation and compares it to New York State’s mean score. Mean SES was based on the census track and census block that corresponds with a state’s mean. Patients were classified by their self-identified race and ethnicity as H, NHB, NHW and other. Patient information was de-identified and stored in a password-protected and encrypted Microsoft excel file. Institutional review board approval was obtained from the Albert Einstein College of Medicine. Statistical Analysis
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Descriptive analysis was performed on the demographic and clinical characteristics of the four ethnic groups. For the continuous variables, mean and standard deviation for each group were reported, and the difference across four groups was tested by ANOVA. When the continuous variables were not normally distributed, median and range were reported, and Kruskal-Wallis test was used. For the categorical variables, frequency and percentage were reported and Chi-square test was used to test the group difference. A proportional odds model was used to calculate the pairwise odds ratio for a patient having higher Gleason score between different ethnic groups. A logistic regression model was used for calculating the pairwise odds ratio for a patient having metastatic disease comparing different ethnic groups. Results were expressed as odds ratios and 95% confidence intervals. The odds ratios and P-values for pairwise comparison were adjusted for multiple comparison by the Tukey method. Group specific survival curves were calculated using the Kaplan-Meier method and the group differences were analyzed by the log-rank test. All tests were 2-sided, with P<0.05 considered statistically significant. Results
A total of 2,352 patients were identified. There were 1046 NHBs, 778 Hs, 486 NHWs and 42 other (O) in the cohort. The mean age at diagnosis (Table 1) differed between these groups (H 63.2, NHB 63.4, NHW 67, O 63 p <0.0001). The proportion of men below the mean SES also differed between races (H 92.8%, NHB 91.3%, NHW 56.6%, O 75% p<0.0001). Median PSA and T-stage were similar at diagnosis across races (Table 2). However, Gleason score was significantly different across races (p =0.0005). The proportion of men with metastatic disease at diagnosis also differed significantly in these groups (H 7.5%, NHB 9.0%, NHW 4.3%, O 9.5%, p = 0.0139).
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The pairwise comparison allowed direct comparison between groups. The age at diagnosis and SES were significantly different (p <0.0001) in the NHW group when compared directly to the NHB and H groups. The odds ratio for higher Gleason score at presentation (Table 3) between NHB vs NHW was 1.592 (p <0.001), and was 1.378 for H vs NHW (p = 0.0200). Pairwise comparison for metastatic disease at diagnosis (Table 4) showed an odds ratio of 2.186 for NHB vs NHW (p = 0.0087). H men had an odds ratio of 1.784 as compared with NHW but was not significant, suggesting the odds of metastatic disease at diagnosis in our population are not different between H and NHW (p = 0.1197). Furthermore, when we specifically adjusted for SES, the odds ratio for higher Gleason score at presentation was still significant for NHB vs NHW (adjusted odds ratio 1.550, p = 0.001) but was of borderline significance for H vs NHW (adjusted odds ratio 1.363, p = 0.0564) (Table 5). After adjustment for SES, the pairwise comparison for metastatic disease at diagnosis was not significant amongst all groups (Table 6). Overall survival (Figure 1) by ethnicity showed no significant difference between groups (p = 0.2401). Of note, the survival data was incomplete, with a quarter of patients lacking follow-up time points. PCaspecific survival data was not available.
Discussion
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In a contemporary, diverse, inner-city cohort of men with PCa, our analysis found significant differences in both sociodemographic and clinicopathologic variables at the time of PCa diagnosis among different races. Compared with NHW, both NHB and Hispanic patients presented with disease at an earlier age and with higher Gleason scores. Additionally, NHB were more likely to present with metastatic disease than NHWs. There was a trend toward a higher incidence of metastatic disease in H compared with NHW, although this did not reach statistical significance. However, when adjusted for SES, there was no difference in incidence of metastatic disease at presentation. This data reinforces previously established findings that minority patients suffer disproportionately from PCa and PCa-related outcomes, but suggests that difference in SES contribute to these adverse outcomes.
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While the above findings regarding NHB men are previously described in the literature, our data point to a novel finding that H men also present with more aggressive disease at younger ages. This finding is even more surprising, given the “Hispanic Paradox” of lower cancer specific mortality despite disadvantageous SES markers that would predict otherwise. One possible explanation for this dichotomy is that the H population itself is very mixed. There is diversity amongst Hispanic groups in cancer incidence; population studies of Hispanic-Americans show that Cubans and Puerto Ricans have significantly higher rates of cancer as compared to other Hispanic groups.15 In Florida, the PCa mortality among Dominicans was nearly double as compared to NHWs and highest among all Hispanic groups.15 Interestingly, the genetic makeup of Dominicans is approximately 40% African16 and for Puerto Ricans, this number is 21%17; these two populations make up the majority of the Hispanic population in the Bronx. The link to African ancestry may explain why Hispanic patients at our medical center have more aggressive
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disease. Interestingly, a similar analysis of patients with liver cancer, concluded that the Hispanics in the Bronx, do not reflect the national data, such as SEER.18
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The U.S. Hispanic population is very heterogeneous. It is comprised of three different ancestral groups: Native American, European, and West African.19,20 Across the U.S., the contribution of the ancestral groups differs21; subgroups in the Northeast and Southeast U.S. have more West African ancestry while those in the Southwest have more Native American ancestry.22 These geographical ancestral variations must be considered when interpreting outcomes data for H patients, especially as they currently compromise 18%23 of the total U.S. population. As ancestral lineage is now determined genetically rather than subjective self-reporting, different ethnic outcomes of PCa are becoming more granular and we believe our findings are germane to our evolving understanding of PCa outcome discrepancies.
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The unfavorable disease characteristics of our NHB and H patients suggest that the current screening paradigm for AA and H patients may be inadequate. Controversy exists about when to start screening patients from high-risk communities. Current United States Preventative Services Task Force (USPSTF) guidelines suggest a joint patient-physician discussion for men between 55-69 about the harms/benefits of PSA screening and no screening for men over 70.24 Since the publication of these recommendations in 2012, absolute rates of PSA screening have dropped 3-10% across various geographic areas and age groups.25,26 Specifically in AA men, PSA screening has decreased by 25%.27 Our data support these findings as the number of diagnosed cases of PCa detected from 2012-2014 in our center sharply decreased from pre-USPSTF recommendations. (Table 1)
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Conversely, the National Comprehensive Cancer Network (NCCN) guidelines recommend screening beginning at age 45 with intervals dependent on PSA value; PSA <1 ng/ml are recommended to be screened every 2 to 4 years, and PSA between 1 – 3, every 1 to 2-years screening.28 Per NCCN, for NHB it is “reasonable” to begin discussing PSA screening earlier and to consider more frequent screening intervals (annually) but no definitive strategy is recommended. NHB are diagnosed with PCa at an earlier age,3,4,29 with a lower optimal PSA threshold of detection of closer to 1.9.30 The current guidelines are not adequate in detecting PCa in our minority patients, especially Hispanic patients who have no formal recommendations for earlier or more aggressive screening. Our minority patients had significantly lower SES than that of Caucasians, with 90% of both NHB and H patients being under the state average SES. Lower SES is associated with worse cancer outcomes.31,32 Even in countries with universal healthcare such as Sweden, imaging and aggressive treatment are performed more frequently in PCa patients with higher SES, with significantly better associated prostate cancer-specific mortality.33 In a retrospective cohort study in California, men of lower SES were less likely to undergo radical treatment for the management of their PCa. Even when radical treatment was administered, men with lower relative SES had worse PCa-specific mortality rates than men of higher SES.34 In addition, lower SES also increases the risk of presenting with metastatic PCa, even when controlling for race.13
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Based on these previous findings, our ethnic minority patients are at a dual risk for poor oncologic outcomes due to both race and SES.
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When overall survival was compared by ethnicity, we did not find a significant difference. However, survival data was incomplete and is difficult to interpret. As survival is related to stage, we believe the increased incidence of metastatic disease at diagnosis represents a clear disparity negatively impacting the minority population at our center.
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We recognize that the current study has certain limitations. Firstly, it is a single institution study, which introduces bias and limits generalizability. Furthermore, it was a retrospective analysis with its inherent biases. Important variables including different Hispanic sub-groups, lifestyle factors, family history or long-term survival of these patients were not ascertainable.
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Despite these limitations, we believe our study adds to the current understanding of PCa outcome disparities among different races and ethnicities. Such differences at diagnosis, particularly in percentage of patients with metastatic disease, confirm that minority patients are at risk for inferior PCa outcomes. However, the exact mechanisms that explain these adverse outcomes remain to be elucidated. Future studies will focus on correlation between clinical presentation and hard endpoints, such as metastasis and PCa-related death. In addition, place of birth information should be noted in future PCa outcome studies as the H population is extremely heterogeneous.
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Conclusions In a large urban academic tertiary care center, men of different racial groups have significant differences at the time of presentation of newly diagnosed PCa. African-American and Hispanic men tend to have disease at earlier ages, lower SES, higher Gleason scores and higher numbers of patients with metastatic disease at presentation. Our data is novel in that we show that Hispanic men also present with aggressive disease, and along with AA, are likely at risk for inferior outcomes.
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Tables and Figures
Table 1: Sociodemographic Data H (n = 778)
NHW (n= 486)
Age at Diagnosis Mean (STD)
63.4 (9.6)
63.2 (9.3)
67 (9.7)
63 (9.1)
700 (92.8)
252 (56.6)
30 (75)
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929 (91.3)
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Socioeconomic Status (SES) Below Average N (%)
O (n=42)
P-value
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NHB (n= 1046)
<0.0001
<0.0001
Year of Diagnosis 208 (19.9)
97 (12.5)
111 (22.8)
7 (16.7)
2006-8 N (%)
351 (33.6)
232 (29.8)
183 (37.7)
10 (23.8)
2009-11 N (%)
339 (32.4)
265 (34.1)
138 (28.4)
17 (40.5)
2012-14 N (%)
148 (14.1)
54 (11.1)
8 (19)
NHW (n=486)
O (n=42)
P-value
6.4 (3.9, 1500)
0.0768
0.0005
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2003-5 N (%)
184 (23.7)
<0.0001
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Table 2: Clinicopathologic Data
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NHB (n=1046)
Median (Min, Max)
8.4 (0.9, 2630)
H (n = 778)
PSA at Diagnosis 8 (1.9, 3600)
7.2 (1.8, 2630)
Gleason Score
≤6 N (%)
399 (39.1)
327 (42.8)
251 (52.2)
21 (50.0)
7 N (%)
442 (43.3)
316 (41.4)
161 (33.5)
14 (33.3)
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8-10 N (%)
180 (17.6)
121 (15.8)
69 (14.3)
7 (16.7)
T-Stage 42 (9.3)
47 (11.6)
28 (16.1)
3 (12.0)
T2b-T2c N (%)
316 (69.6)
262 (64.7)
113 (64.9)
18 (72)
T3/T4 N (%)
96 (21.1)
96 (23.7)
33 (19.0)
4 (16.0)
0.2366
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T1-T2a N (%)
Metastatic Disease at Diagnosis 94 (9)
58 (7.5)
21 (4.3)
4 (9.5)
0.0139
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N (%)
Table 3: Unadjusted pairwise Odds Ratio for Higher Gleason Score at Diagnosis Adjusted Odds Ratio
Adjusted P-value
NHB vs H
1.155 (0.917, 1.455)
0.3746
NHB vs NHW
1.592 (1.214, 2.087)
<0.0001
1.419 (0.658, 3.060)
0.6465
1.378 (1.036, 1.832)
0.0200
1.228 (0.567, 2.662)
0.9039
H vs NHW H vs O NHW vs O
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NHB vs O
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Pairs
0.891 (0.406, 1.957)
0.9818
Pairs
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Table 4: Unadjusted Odds Ratio for Metastatic Disease at Diagnosis Adjusted Odds Ratio
Adjusted P-value
NHB vs H
1.226 (0.784, 1.917)
0.6465
NHB vs NHW
2.186 (1.156, 4.133)
0.0087
NHB vs O
0.938 (0.236, 3.724)
0.9994
H vs NHW
1.784 (0.911, 3.492)
0.1197
H vs O
0.765 (0.190, 3.089)
0.9608
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NHW vs O
0.429 (0.099, 1.860)
0.4485
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Table 5: Pairwise Odds Ratio for Higher Gleason Score at Diagnosis, Adjusted for SES Pairs Adjusted Odds Ratio Adjusted P-value NHB vs H 0.4908 1.138 (0.900, 1.438) NHB vs NHW 0.001 1.550 (1.148, 2.094) NHB vs O 0.726 1.376 (0.625, 3.026) H vs NHW 0.0564 1.363 (0.994, 1.868) H vs O 0.9272 1.209 (0.547, 2.675) NHW vs O 0.9814 0.887 (0.395, 1.992)
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Table 6: Pairwise Odds Ratio for Metastatic Disease at Diagnosis, Adjusted for SES Pairs Adjusted Odds Ratio Adjusted P-value NHB vs H 0.6094 1.241 (0.790, 1.948) NHB vs NHW 0.0971 1.861 (0.931, 3.722) NHB vs O 0.9856 0.829 (0.207, 3.323) H vs NHW 0.4798 1.500 (0.724, 3.108) H vs O 0.8821 0.668 (0.164, 2.726) NHW vs O 0.5019 0.445 (0.100, 1.974)
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Figure 1: Overall Survival by Ethnicity: (Kaplan-Meier Curve)
*P-value: 0.2401
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2000-2014: PRELIMINARY RESULTS FROM THE FIRST AUA DATA GRANT. The Journal of urology. 2016;195(4, Supplement):e543. Carroll PH, Mohler JL. NCCN Guidelines Updates: Prostate Cancer and Prostate Cancer Early Detection. Journal of the National Comprehensive Cancer Network : JNCCN. 2018;16(5s):620-623. Metcalfe C, Evans S, Ibrahim F, et al. Pathways to diagnosis for Black men and White men found to have prostate cancer: the PROCESS cohort study. Br J Cancer. 2008;99(7):1040-1045. Sutton SS, Crawford ED, Moul JW, Hardin JW, Kruep E. Determining optimal prostatespecific antigen thresholds to identify an increased 4-year risk of prostate cancer development: an analysis within the Veterans Affairs Health Care System. World journal of urology. 2016;34(8):1107-1113. Du XL, Fang S, Coker AL, et al. Racial disparity and socioeconomic status in association with survival in older men with local/regional stage prostate carcinoma: findings from a large community-based cohort. Cancer. 2006;106(6):1276-1285. Woods LM, Rachet B, Coleman MP. Origins of socio-economic inequalities in cancer survival: a review. Annals of oncology : official journal of the European Society for Medical Oncology. 2006;17(1):5-19. Berglund A, Garmo H, Robinson D, et al. Differences according to socioeconomic status in the management and mortality in men with high risk prostate cancer. European Journal of Cancer. 2012;48(1):75-84. Hellenthal NJ, Parikh-Patel A, Bauer K, Ralph W, deVere W, Koppie TM. Men of Higher Socioeconomic Status Have Improved Outcomes After Radical Prostatectomy for Localized Prostate Cancer. Urology. 2010;76(6):1409-1413.
S1558-7673(18)30592-5
DOI:
https://doi.org/10.1016/j.clgc.2018.12.003
Reference:
CLGC 1182
To appear in:
Clinical Genitourinary Cancer
Received Date: 9 August 2018 Revised Date:
30 November 2018
Accepted Date: 1 December 2018
Please cite this article as: Suresh T, Sharma J, Goel S, Kovac E, Gao Q, Gartrell B, Patient Characteristics at Time of Prostate Cancer Diagnosis in Different Races at an Academic Center Serving a Diverse Population, Clinical Genitourinary Cancer (2019), doi: https://doi.org/10.1016/ j.clgc.2018.12.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Patient Characteristics at Time of Prostate Cancer Diagnosis in Different Races at an Academic Center Serving a Diverse Population Tejas Suresh M.D., 4Janaki Sharma M.D., 4Sanjay Goel M.D., 3Evan Kovac M.D., 2Qi Gao Ph.D, Benjamin Gartrell M.D. 1 Departments of Medicine, 2Epidemiology, 3Urology and 4Medical Oncology; Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA 1
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Corresponding Author Tejas Suresh M.D. Yale University School of Medicine 333 Cedar Street Room WWW 209 New Haven, CT 06520 Phone: 475 – 224 - 0734
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Clinical Practice Points
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In the United States, prostate cancer (PCa) incidence and death rate is greater in non-Hispanic Blacks (NHB) than non-Hispanic Whites (NHW), and slightly lower in Hispanic (H) than NHW. In our study of a large urban academic tertiary care center, men of different racial groups have significant differences at the time of presentation of newly diagnosed PCa. African-American and Hispanic men tend to have disease at earlier ages, lower SES, higher Gleason scores and higher numbers of patients with metastatic disease at presentation. Our data is novel in that we show that Hispanic men also present with aggressive disease, and along with AA, are likely at risk for inferior outcomes. This may impact thought on race/ethnicity-specific screening recommendations.
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Abstract Background:
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In the United States, prostate cancer (PCa) incidence and death rate is greater in non-Hispanic Blacks (NHB) than non-Hispanic Whites (NHW), and slightly lower in Hispanic (H) than NHW. We sought to compare the sociodemographic and baseline prognostic factors at the time of PCa diagnosis in different races/ethnicities at a large, academic center serving an ethnically diverse population.
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Methods:
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The Montefiore Medical Center (MMC) Cancer Registry was used to generate a comprehensive list of all patients with PCa diagnosed from the years 2004 to 2014. Clinical Looking Glass (a proprietary searchable database of patient information) and individual patient chart review was used to obtain data including age at diagnosis, socioeconomic status (SES), clinical Gleason score, clinical stage and PSA at diagnosis. Patients were classified by self-identified race/ethnicity as H, NHB, NHW or other(O). Chi-square test was used for categorical variables, while ANOVA or Kruskal-Wallis test was used for continuous variables. All analysis was performed using SAS 9.3 (Cary, NC). Results:
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We identified 2352 patients with newly diagnosed PCa during the study period: 778 (H), 1046 (NHB), 486 (NHW) and 42 (O). NHW men were significantly older at diagnosis (H 63.2, NHB 63.4, NHW 67, O 63.0, p < 0.0001). Mean SES for H and NHB men were significantly lower (SES below the average: H 92.8%, NHB 91.3%, NHW 56.6%, O 75%, p<0.0001). Gleason score at diagnosis differed between these race groups (Gleason ≤6 PCa: H 42.8%, NHB 39.1%, NHW 52.2%, O 50%; Gleason 8-10: H 15.8%, NHB 17.6%, NHW 14.3%, O 16.7%, p=0.0005). The proportion of men with metastatic disease at diagnosis also differed significantly between groups (H 7.5%, NHB 9.0%, NHW 4.3%, O 9.5%, p=0.0139). Using pairwise comparison, the odds ratio for higher Gleason score at presentation between NHB vs NHW was 1.592 (p <0.001), and was 1.378 for H vs NHW (p = 0.0200). Pairwise comparison for metastatic disease at diagnosis showed an odds ratio of 2.186 for NHB vs NHW (p = 0.0087). After adjusting for SES, the odds ratio for higher Gleason score comparing NHB vs NHW is 1.55 (p=0.001). Although the odds of metastatic disease were higher in H compared to NHW (OR=1.784), they were not statistically different (p = 0.1197). Conclusions: At our center, the clinical features of men from different racial groups differ significantly at the time of newly diagnosed prostate cancer. Differences include age at diagnosis, SES, Gleason score and proportion with metastatic disease. Our pairwise comparisons between different
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ethnic groups suggest that prostate cancer in Hispanic men may be more similar to NHB than to NHW patients and are generally more aggressive at the time of diagnosis.
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Introduction and Background
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Prostate cancer (PCa) is the most commonly diagnosed non-skin cancer in men in the United States, and it is estimated that 161,360 men were diagnosed in 2017 and 26,730 died of their disease.1 In general, cancer related mortality has declined over the last several decades, but the decline has been consistently greater in NHW versus H or NHB populations.2 In the United States, PCa incidence and death rate differ among races and ethnicities.1
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African-Americans (AA) have higher incidence1, earlier age at diagnoses3,4 and increased death rate1 from PCa. The incidence is 73% higher and the rate of death is 2.3-fold higher in AA men in the United States than in NHW men.1 According to one analysis of the Surveillance, Epidemiology, and End Results (SEER) Database from 2006-2012, 5% of black patients and 4% of white patients had distant disease at the time of diagnosis.1 Another analysis of SEER found that black patients were more likely to present with metastatic PCa compared to non-black patients in the years 2004-2011 with an adjusted odds ratio of 1.65; P<0.001).5 An analysis of SEER data from metropolitan Detroit found that the odds ratio for the incidence of distant PCa was 3-5x higher for black compared to non-black patients.6 In the same publication, black patients undergoing radical prostatectomy had greater tumor volumes compared to non-black patients between the ages of 40-69, but autopsy data showed that PCa incidence at autopsy was similar between black and non-black patients. This suggests an earlier transition to biologically aggressive PCa in AA patients. AA patients with clinical American Urological Association (AUA) very low risk and low risk PCa who would meet criteria for active surveillance but elect to undergo immediate radical prostatectomy are more likely to have adverse pathological upgrading/upstaging compared to other races.7 While socioeconomic factors and limitations in access to care likely contribute to PCa disparities among minority communities in the United States8, biological differences including differential expression of PCa associated genes and higher likelihood of “triple-negative” prostate cancer in AA men have also been reported.9,10 Unlike NHBs, Hispanic (H) men in the United States have a lower PCa incidence and death rate than NHWs.11 This lower cancer related mortality rate among H populations, despite inferior SES, has been reported across multiple tumor types and is known as the “Hispanic Paradox.”12 According to data from SEER from 2008-2012, distant disease was present at diagnosis in 6% of H and 4% of NHW.11 Recent data from the national cancer database indicates a higher incidence of metastatic PCa at diagnosis in H (6.2%) and NHB (5.9%) compared to NHW (3.6%) and an inverse relationship of socioeconomic status and the odds of presenting with metastatic disease.13 Additionally, a recent analysis of SWOG clinical trial participants of Hispanic ethnicity, suggests no difference in overall survival between H and NHW PCa patients when adjusted for multiple comparisons.14 Montefiore Medical Center (MMC) is a large tertiary care center serving a diverse, urban population composed primarily of minorities in the Bronx. We have established an institutional PCa database. Here we report the socioeconomic, demographic and baseline prognostic factors at the time of PCa diagnosis among different races and ethnicities at our institution.
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Patients and Methods Creation of Database
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PCa patients were identified through the MMC cancer registry. Information was collected on patients diagnosed at our center from 2004 to 2014. The Clinical Looking Glass (a proprietary searchable database of patient information) and individual patient chart review were used to obtain data including race, age at diagnosis, year of diagnosis, socioeconomic status (SES, associated with the census track in which the patient lives), clinical Gleason score, clinical T stage at diagnosis and PSA at diagnosis. SES combines information on patient income, housing value, education and occupation and compares it to New York State’s mean score. Mean SES was based on the census track and census block that corresponds with a state’s mean. Patients were classified by their self-identified race and ethnicity as H, NHB, NHW and other. Patient information was de-identified and stored in a password-protected and encrypted Microsoft excel file. Institutional review board approval was obtained from the Albert Einstein College of Medicine. Statistical Analysis
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Descriptive analysis was performed on the demographic and clinical characteristics of the four ethnic groups. For the continuous variables, mean and standard deviation for each group were reported, and the difference across four groups was tested by ANOVA. When the continuous variables were not normally distributed, median and range were reported, and Kruskal-Wallis test was used. For the categorical variables, frequency and percentage were reported and Chi-square test was used to test the group difference. A proportional odds model was used to calculate the pairwise odds ratio for a patient having higher Gleason score between different ethnic groups. A logistic regression model was used for calculating the pairwise odds ratio for a patient having metastatic disease comparing different ethnic groups. Results were expressed as odds ratios and 95% confidence intervals. The odds ratios and P-values for pairwise comparison were adjusted for multiple comparison by the Tukey method. Group specific survival curves were calculated using the Kaplan-Meier method and the group differences were analyzed by the log-rank test. All tests were 2-sided, with P<0.05 considered statistically significant. Results
A total of 2,352 patients were identified. There were 1046 NHBs, 778 Hs, 486 NHWs and 42 other (O) in the cohort. The mean age at diagnosis (Table 1) differed between these groups (H 63.2, NHB 63.4, NHW 67, O 63 p <0.0001). The proportion of men below the mean SES also differed between races (H 92.8%, NHB 91.3%, NHW 56.6%, O 75% p<0.0001). Median PSA and T-stage were similar at diagnosis across races (Table 2). However, Gleason score was significantly different across races (p =0.0005). The proportion of men with metastatic disease at diagnosis also differed significantly in these groups (H 7.5%, NHB 9.0%, NHW 4.3%, O 9.5%, p = 0.0139).
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The pairwise comparison allowed direct comparison between groups. The age at diagnosis and SES were significantly different (p <0.0001) in the NHW group when compared directly to the NHB and H groups. The odds ratio for higher Gleason score at presentation (Table 3) between NHB vs NHW was 1.592 (p <0.001), and was 1.378 for H vs NHW (p = 0.0200). Pairwise comparison for metastatic disease at diagnosis (Table 4) showed an odds ratio of 2.186 for NHB vs NHW (p = 0.0087). H men had an odds ratio of 1.784 as compared with NHW but was not significant, suggesting the odds of metastatic disease at diagnosis in our population are not different between H and NHW (p = 0.1197). Furthermore, when we specifically adjusted for SES, the odds ratio for higher Gleason score at presentation was still significant for NHB vs NHW (adjusted odds ratio 1.550, p = 0.001) but was of borderline significance for H vs NHW (adjusted odds ratio 1.363, p = 0.0564) (Table 5). After adjustment for SES, the pairwise comparison for metastatic disease at diagnosis was not significant amongst all groups (Table 6). Overall survival (Figure 1) by ethnicity showed no significant difference between groups (p = 0.2401). Of note, the survival data was incomplete, with a quarter of patients lacking follow-up time points. PCaspecific survival data was not available.
Discussion
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In a contemporary, diverse, inner-city cohort of men with PCa, our analysis found significant differences in both sociodemographic and clinicopathologic variables at the time of PCa diagnosis among different races. Compared with NHW, both NHB and Hispanic patients presented with disease at an earlier age and with higher Gleason scores. Additionally, NHB were more likely to present with metastatic disease than NHWs. There was a trend toward a higher incidence of metastatic disease in H compared with NHW, although this did not reach statistical significance. However, when adjusted for SES, there was no difference in incidence of metastatic disease at presentation. This data reinforces previously established findings that minority patients suffer disproportionately from PCa and PCa-related outcomes, but suggests that difference in SES contribute to these adverse outcomes.
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While the above findings regarding NHB men are previously described in the literature, our data point to a novel finding that H men also present with more aggressive disease at younger ages. This finding is even more surprising, given the “Hispanic Paradox” of lower cancer specific mortality despite disadvantageous SES markers that would predict otherwise. One possible explanation for this dichotomy is that the H population itself is very mixed. There is diversity amongst Hispanic groups in cancer incidence; population studies of Hispanic-Americans show that Cubans and Puerto Ricans have significantly higher rates of cancer as compared to other Hispanic groups.15 In Florida, the PCa mortality among Dominicans was nearly double as compared to NHWs and highest among all Hispanic groups.15 Interestingly, the genetic makeup of Dominicans is approximately 40% African16 and for Puerto Ricans, this number is 21%17; these two populations make up the majority of the Hispanic population in the Bronx. The link to African ancestry may explain why Hispanic patients at our medical center have more aggressive
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disease. Interestingly, a similar analysis of patients with liver cancer, concluded that the Hispanics in the Bronx, do not reflect the national data, such as SEER.18
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The U.S. Hispanic population is very heterogeneous. It is comprised of three different ancestral groups: Native American, European, and West African.19,20 Across the U.S., the contribution of the ancestral groups differs21; subgroups in the Northeast and Southeast U.S. have more West African ancestry while those in the Southwest have more Native American ancestry.22 These geographical ancestral variations must be considered when interpreting outcomes data for H patients, especially as they currently compromise 18%23 of the total U.S. population. As ancestral lineage is now determined genetically rather than subjective self-reporting, different ethnic outcomes of PCa are becoming more granular and we believe our findings are germane to our evolving understanding of PCa outcome discrepancies.
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The unfavorable disease characteristics of our NHB and H patients suggest that the current screening paradigm for AA and H patients may be inadequate. Controversy exists about when to start screening patients from high-risk communities. Current United States Preventative Services Task Force (USPSTF) guidelines suggest a joint patient-physician discussion for men between 55-69 about the harms/benefits of PSA screening and no screening for men over 70.24 Since the publication of these recommendations in 2012, absolute rates of PSA screening have dropped 3-10% across various geographic areas and age groups.25,26 Specifically in AA men, PSA screening has decreased by 25%.27 Our data support these findings as the number of diagnosed cases of PCa detected from 2012-2014 in our center sharply decreased from pre-USPSTF recommendations. (Table 1)
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Conversely, the National Comprehensive Cancer Network (NCCN) guidelines recommend screening beginning at age 45 with intervals dependent on PSA value; PSA <1 ng/ml are recommended to be screened every 2 to 4 years, and PSA between 1 – 3, every 1 to 2-years screening.28 Per NCCN, for NHB it is “reasonable” to begin discussing PSA screening earlier and to consider more frequent screening intervals (annually) but no definitive strategy is recommended. NHB are diagnosed with PCa at an earlier age,3,4,29 with a lower optimal PSA threshold of detection of closer to 1.9.30 The current guidelines are not adequate in detecting PCa in our minority patients, especially Hispanic patients who have no formal recommendations for earlier or more aggressive screening. Our minority patients had significantly lower SES than that of Caucasians, with 90% of both NHB and H patients being under the state average SES. Lower SES is associated with worse cancer outcomes.31,32 Even in countries with universal healthcare such as Sweden, imaging and aggressive treatment are performed more frequently in PCa patients with higher SES, with significantly better associated prostate cancer-specific mortality.33 In a retrospective cohort study in California, men of lower SES were less likely to undergo radical treatment for the management of their PCa. Even when radical treatment was administered, men with lower relative SES had worse PCa-specific mortality rates than men of higher SES.34 In addition, lower SES also increases the risk of presenting with metastatic PCa, even when controlling for race.13
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Based on these previous findings, our ethnic minority patients are at a dual risk for poor oncologic outcomes due to both race and SES.
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When overall survival was compared by ethnicity, we did not find a significant difference. However, survival data was incomplete and is difficult to interpret. As survival is related to stage, we believe the increased incidence of metastatic disease at diagnosis represents a clear disparity negatively impacting the minority population at our center.
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We recognize that the current study has certain limitations. Firstly, it is a single institution study, which introduces bias and limits generalizability. Furthermore, it was a retrospective analysis with its inherent biases. Important variables including different Hispanic sub-groups, lifestyle factors, family history or long-term survival of these patients were not ascertainable.
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Despite these limitations, we believe our study adds to the current understanding of PCa outcome disparities among different races and ethnicities. Such differences at diagnosis, particularly in percentage of patients with metastatic disease, confirm that minority patients are at risk for inferior PCa outcomes. However, the exact mechanisms that explain these adverse outcomes remain to be elucidated. Future studies will focus on correlation between clinical presentation and hard endpoints, such as metastasis and PCa-related death. In addition, place of birth information should be noted in future PCa outcome studies as the H population is extremely heterogeneous.
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Conclusions In a large urban academic tertiary care center, men of different racial groups have significant differences at the time of presentation of newly diagnosed PCa. African-American and Hispanic men tend to have disease at earlier ages, lower SES, higher Gleason scores and higher numbers of patients with metastatic disease at presentation. Our data is novel in that we show that Hispanic men also present with aggressive disease, and along with AA, are likely at risk for inferior outcomes.
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Tables and Figures
Table 1: Sociodemographic Data H (n = 778)
NHW (n= 486)
Age at Diagnosis Mean (STD)
63.4 (9.6)
63.2 (9.3)
67 (9.7)
63 (9.1)
700 (92.8)
252 (56.6)
30 (75)
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Socioeconomic Status (SES) Below Average N (%)
O (n=42)
P-value
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NHB (n= 1046)
<0.0001
<0.0001
Year of Diagnosis 208 (19.9)
97 (12.5)
111 (22.8)
7 (16.7)
2006-8 N (%)
351 (33.6)
232 (29.8)
183 (37.7)
10 (23.8)
2009-11 N (%)
339 (32.4)
265 (34.1)
138 (28.4)
17 (40.5)
2012-14 N (%)
148 (14.1)
54 (11.1)
8 (19)
NHW (n=486)
O (n=42)
P-value
6.4 (3.9, 1500)
0.0768
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2003-5 N (%)
184 (23.7)
<0.0001
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Table 2: Clinicopathologic Data
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NHB (n=1046)
Median (Min, Max)
8.4 (0.9, 2630)
H (n = 778)
PSA at Diagnosis 8 (1.9, 3600)
7.2 (1.8, 2630)
Gleason Score
≤6 N (%)
399 (39.1)
327 (42.8)
251 (52.2)
21 (50.0)
7 N (%)
442 (43.3)
316 (41.4)
161 (33.5)
14 (33.3)
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8-10 N (%)
180 (17.6)
121 (15.8)
69 (14.3)
7 (16.7)
T-Stage 42 (9.3)
47 (11.6)
28 (16.1)
3 (12.0)
T2b-T2c N (%)
316 (69.6)
262 (64.7)
113 (64.9)
18 (72)
T3/T4 N (%)
96 (21.1)
96 (23.7)
33 (19.0)
4 (16.0)
0.2366
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T1-T2a N (%)
Metastatic Disease at Diagnosis 94 (9)
58 (7.5)
21 (4.3)
4 (9.5)
0.0139
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N (%)
Table 3: Unadjusted pairwise Odds Ratio for Higher Gleason Score at Diagnosis Adjusted Odds Ratio
Adjusted P-value
NHB vs H
1.155 (0.917, 1.455)
0.3746
NHB vs NHW
1.592 (1.214, 2.087)
<0.0001
1.419 (0.658, 3.060)
0.6465
1.378 (1.036, 1.832)
0.0200
1.228 (0.567, 2.662)
0.9039
H vs NHW H vs O NHW vs O
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NHB vs O
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Pairs
0.891 (0.406, 1.957)
0.9818
Pairs
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Table 4: Unadjusted Odds Ratio for Metastatic Disease at Diagnosis Adjusted Odds Ratio
Adjusted P-value
NHB vs H
1.226 (0.784, 1.917)
0.6465
NHB vs NHW
2.186 (1.156, 4.133)
0.0087
NHB vs O
0.938 (0.236, 3.724)
0.9994
H vs NHW
1.784 (0.911, 3.492)
0.1197
H vs O
0.765 (0.190, 3.089)
0.9608
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NHW vs O
0.429 (0.099, 1.860)
0.4485
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Table 5: Pairwise Odds Ratio for Higher Gleason Score at Diagnosis, Adjusted for SES Pairs Adjusted Odds Ratio Adjusted P-value NHB vs H 0.4908 1.138 (0.900, 1.438) NHB vs NHW 0.001 1.550 (1.148, 2.094) NHB vs O 0.726 1.376 (0.625, 3.026) H vs NHW 0.0564 1.363 (0.994, 1.868) H vs O 0.9272 1.209 (0.547, 2.675) NHW vs O 0.9814 0.887 (0.395, 1.992)
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Table 6: Pairwise Odds Ratio for Metastatic Disease at Diagnosis, Adjusted for SES Pairs Adjusted Odds Ratio Adjusted P-value NHB vs H 0.6094 1.241 (0.790, 1.948) NHB vs NHW 0.0971 1.861 (0.931, 3.722) NHB vs O 0.9856 0.829 (0.207, 3.323) H vs NHW 0.4798 1.500 (0.724, 3.108) H vs O 0.8821 0.668 (0.164, 2.726) NHW vs O 0.5019 0.445 (0.100, 1.974)
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Figure 1: Overall Survival by Ethnicity: (Kaplan-Meier Curve)
*P-value: 0.2401
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