African American vs Caucasian race/ethnicity in adrenocortical carcinoma patients
Andrea Panunzio1,2, Stefano Tappero2,3,4, Lukas Hohenhorst2,5, Cristina Cano Garcia2,6, Mattia Piccinelli2,7, Francesco Barletta2,8, Zhe Tian2, Alessandro Tafuri1, Alberto Briganti8, Ottavio De Cobelli7, Felix K H Chun6, Derya Tilki5,9,10, Carlo Terrone3,4, Fred Saad2, Shahrokh F Shariat11,12,13,14, Isabelle Bourdeau15, Maria Angela Cerruto1, Alessandro Antonelli1 and Pierre I Karakiewicz2
1Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy
2Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada
3Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genova, Italy 4Department of Urology, IRCCS Policlinico San Martino, Genova, Italy
5Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
6Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany
7Department of Urology, IEO European Institute of Oncology, IRCCS, Milan, Italy
8Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy 9Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
10Department of Urology, Koc University Hospital, Istanbul, Turkey
11Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
12Departments of Urology, Weill Cornell Medical College, New York, New York, USA
13Department of Urology, University of Texas Southwestern, Dallas, Texas, USA
14Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan
15Division of Endocrinology, Department of Medicine and Research Center, Centre hospitalier de l’Université de Montreal (CHUM), Montreal, Canada
Correspondence should be addressed to A Panunzio: andrea.panunzio@studenti.univr.it
Abstract
In some primaries, African American race/ethnicity predisposes to higher stage and worse survival. We tested for differences in cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients with adrenocortical carcinoma (ACC) according to African American vs Caucasian race/ethnicity. We hypothesized that African Americans present with higher tumor stage and grade, do not receive the same treatment, and experience worse oncological outcomes than Caucasians. Within Surveillance, Epidemiology, and End Results database, we identified 1016 ACC patients: 123 (12.1%) African Americans vs 893 (87.9%) Caucasians. Propensity score matching (PSM) (age, sex, marital status, grade, T, N, and M stages, and treatment type), Poisson-smoothed cumulative incidence plots, and competing risk regression (CRR) were used. Compared to Caucasians, African Americans were more frequently unmarried (56.9% vs 35.5%, P < 0.001). No clinically meaningful or statistically significant differences were observed for age, grade, T, N, and M stages, as well as treatment type (all P > 0.05). After PSM (1:4), 123 African Americans and 492 Caucasians remained and were included in CRR analysis. In multivariable CRR models, CSM and OCM rates were not different between the two race/ethnicities (hazard ratio: 0.84, P = 0.3). In African Americans, 5-year CSM rates were 31.2% and 75.3% in European Network for the Study of Adrenal Tumors (ENSAT) stages I-II and III-IV, respectively vs 32.9% and 75.4% in Caucasians. Overall 5-year OCM rates were 11.0% vs 10.1% in respectively African Americans and Caucasians. Unlike other primaries, in ACC, African American race/ethnicity is not associated with higher disease stage at initial diagnosis or worse survival.
Key Words
adrenocortical carcinoma
ACC
African Americans
race
Endocrine-Related Cancer (2023) 30, e220249
| Endocrine-Related | A Panunzio et al. | 30:7 | e220249 |
|---|---|---|---|
| Cancer |
Introduction
African American race/ethnicity represents a well- established determinant of disparities in patient access to care as well as a risk factor for less favorable stage at presentation and worse survival in many urological and non-urological primaries (Haider et al. 2013). This relationship has been tested in lung cancer (Varlotto et al. 2018), breast cancer (Iqbal et al. 2015), renal cell carcinoma (RCC) (Stafford et al. 2008, Luzzago et al. 2020), prostate cancer (PCa) (Fuletra et al. 2018, Li et al. 2018), and urothelial carcinoma (Sung et al. 2019, Wenzel et al. 2021). However, it is unknown whether this relationship also applies to adrenocortical carcinoma (ACC).
To address the above unknown, we tested whether African American race/ethnicity is an independent predictor of higher tumor stage at initial diagnosis and/ or of higher cancer-specific mortality (CSM) in ACC patients. We hypothesized that African Americans may harbor worse stage and higher tumor grade, do not receive the same treatment, and experience higher mortality rates than their Caucasians counterparts. We also quantified the contribution of other-cause mortality (OCM) relative to CSM according to African American vs Caucasian race/ethnicity, in overall as well as in stage- specific analyses. We tested these relationships within Surveillance, Epidemiology, and End Results (SEER) database (2004-2018).
Materials and methods
Study population
The SEER database samples 48% of the USA and approximates the USA in terms of its demographic composition as well as its cancer incidence (Howlader 1975-2018, SEER Statistics, available at https://seer.cancer. gov/csr/1975_2018/, accessed on May 11, 2022). Within the SEER database (2004-2018), we identified patients with histologically confirmed ACC (International Classification of Disease for Oncology (ICD-O-3) site code C74.0/C74.9; histologic code: ‘8370/3: Adrenal cortical carcinoma’, ‘8010/3: Carcinoma, NOS’, and ‘8140/3: Adenocarcinoma, NOS’). Patients aged <18 years, with unknown vital status, as well as autopsy-only cases or race/ ethnicity other than Caucasian or African American, were excluded. These selection criteria resulted in an overall cohort of 1016 assessable patients: 123 African Americans vs 893 Caucasians.
Statistical analysis
Descriptive statistics included frequencies and proportions for categorical variables. Medians and interquartile ranges were reported for continuously coded variables. Wilcoxon rank-sum test, Pearson’s chi-square test, and Fisher’s exact test examined the statistical significance of differences in medians and proportions. We relied on propensity score matching (PSM) to the nearest neighbor between African Americans and Caucasians, reducing the effect of selection bias. Here, PSM was applied for age at diagnosis, sex, marital status, tumor grade, T, N, and M stages, and the type of treatment. A threshold of <0.1 in standardized mean difference, which is indicative of clinically insignificant variability, was used (Austin 2011). Subsequently, cumulative incidence plots and competing risk regression (CRR) models were fitted and tested for differences in CSM between African Americans and Caucasians. Adjustment was made for OCM in addition to standard covariates. Finally, we relied on Poisson-smoothed cumulative incidence plots to depict CSM relative to OCM within the entire cohort, as well as according to two specific European Network for the Study of Adrenal Tumors (ENSAT) (Fassnacht et al. 2018) stage groupings: I-II vs III-IV. All tests were two sided with a level of significance set at P < 0.05. R software environment for statistical computing and graphics (version 4.1.2, R Foundation for Statistical Computing, Vienna, Austria) was used for all analyses (R: the R Project for Statistical Computing, available at https://www.r-project.org/, accessed on May 11, 2022).
Results
Descriptive characteristics of the study population
Compared to Caucasians, African Americans were more frequently unmarried (56.9% vs 35.5%, P < 0.001) (Table 1). No statistically significant or clinically meaningful differences were recorded for age at diagnosis, sex, tumor stage and grade, lymph node invasion, distant metastases, ENSAT stage, and type of treatment. All 123 African American patients were matched in 1:4 fashion with 492 Caucasian patients. After PSM, no statistically significant differences remained (Table 1).
The effect of African American race/ethnicity on CSM across all stages prior to and after PSM
Prior to PSM, 5-year CSM rates were 58.5% vs 59.0% in African Americans and Caucasians (P=0.4), respectively.
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After PSM, 5-year CSM rates were 58.5% vs 57.9% in African Americans and Caucasians (P=0.5; Fig. 1), respectively. After matching, multivariable CRR models addressing CSM, which additionally adjusted for age, sex, marital status, tumor grade, ENSAT stage, type of treatment, and postoperative radiation therapy administration, showed no statistically significant differences between African Americans vs Caucasians: hazard ratio (HR): 0.84 (95% CI: 0.62-1.15, P=0.3; Table 2).
CSM vs OCM according to African American vs Caucasian race/ethnicity after PSM
Poisson-smoothed cumulative incidence plots quantified the relative contribution of CSM vs OCM, in African Americans and subsequently in Caucasians. In both race/ ethnicities, data were stratified according to ENSAT I-II vs ENSAT III-IV stages (Fig. 2). In African Americans, 5-year CSM rates were 31.2% and 75.3% in, respectively, ENSAT
| Prior to propensity score matching | After propensity score matching | ||||
|---|---|---|---|---|---|
| Overall cohort (n = 1016) | Overall cohort (n = 615) | ||||
| African Americans | Caucasians | P-valuea | African Americans | Caucasians | |
| n | 123 (12.1)b | 893 (87.9)b | 123 (20.0)b | 492 (80.0)b | |
| Age at diagnosis (years) | 57 (46-64) | 57 (47-67) | 0.3 | 57 (46-64) | 56 (45-67) |
| Sex | 0.2 | ||||
| Female | 81 (65.9) | 531 (59.5) | 81 (65.9) | 324 (65.9) | |
| Male | 42 (34.1) | 362 (40.5) | 42 (34.1) | 168 (34.1) | |
| Marital status | <0.001 | ||||
| Married | 44 (35.8) | 546 (60.9) | 44 (35.8) | 187 (38.0) | |
| Unmarried | 70 (56.9) | 317 (35.5) | 70 (56.9) | 275 (55.9) | |
| Unknown | 9 (7.3) | 30 (3.6) | 9 (7.3) | 30 (6.1) | |
| T stage | 0.8 | ||||
| T1 | 10 (8.1) | 52 (5.8) | 10 (8.1) | 37 (7.5) | |
| T2 | 45 (36.6) | 356 (39.9) | 45 (36.6) | 199 (40.4) | |
| T3 | 25 (20.3) | 192 (21.5) | 25 (20.3) | 90 (18.3) | |
| T4 | 28 (22.8) | 190 (21.3) | 37 (22.8) | 109 (22.2) | |
| TX | 15 (12.2) | 103 (11.5) | 6 (12.2) | 57 (11.6) | |
| Tumor grade | 0.3 | ||||
| G1-2 | 11 (8.9) | 69 (7.7) | 11 (8.9) | 44 (8.9) | |
| G3-4 | 13 (10.6) | 139 (15.6) | 12 (10.6) | 39 (7.9) | |
| GX | 99 (80.5) | 685 (76.7) | 99 (80.5) | 409 (83.4) | |
| Lymph node invasion | 10 (8.1) | 103 (11.5) | 0.12 | 10 (8.1) | 37 (7.5) |
| Distant metastasis | 50 (40.7) | 328 (36.7) | 0.4 | 50 (40.7%) | 200 (40.7) |
| ENSAT staging groups | 0.6 | ||||
| Stage I | 7 (5.7) | 37 (4.1) | 7 (5.7) | 26 (5.3) | |
| Stage II | 33 (26.8) | 264 (29.6) | 33 (26.8) | 148 (30.1) | |
| Stage III | 30 (24.4) | 219 (24.5) | 30 (24.4) | 95 (19.3) | |
| Stage IV | 50 (40.7) | 328 (36.7) | 50 (40.7) | 200 (40.7) | |
| Unknown | 3 (2.4) | 45 (5.1) | 3 (2.4) | 23 (4.6) | |
| Type of treatment | 0.6 | ||||
| None/unknown | 21 (17.1) | 125 (14.0) | 21 (17.1) | 83 (16.9) | |
| Systemic therapy only | 17 (13.8) | 117 (13.1) | 17 (13.8) | 71 (14.4) | |
| Adrenalectomy only | 47 (38.2) | 395 (44.2) | 47 (38.2) | 182 (37.0) | |
| Adrenalectomy + systemic therapy | 38 (30.9) | 256 (28.7) | 38 (30.9) | 156 (31.7) | |
| Postoperative radiation therapy | 12 (9.8) | 104 (11.6) | 0.5 | 12 (9.8) | 48 (9.8) |
Matching variables: age at diagnosis, sex, marital status, T stage, grade, lymph node invasion, distant metastases, type of treatment, and postoperative radiation therapy administration. Values in bold indicate statistical significance set at P < 0.05.
aWilcoxon rank-sum test, Pearson’s chi-square test, and Fisher’s exact test; bMedian (IQR) or n (%). ENSAT, European Network for the Study of Adrenal Tumors.
1.000
5 year CSM in African Americans: 58.5%
5 year CSM in Caucasians: 57.9%
5 year OCM in African Americans: 11.0%
5 year OCM in Caucasians: 10.1%
0.750
HR 0.90 (0.68-1.18), p=0.5
Probability
0.500
0.250
HR 0.99 (0.54-1.80), p=0.9
0.000
0
12
24
36
48
60
72
84
96
108
120
132
144
156
168
180
Caucasians
492
281
199
150
122
103
81
69
57
45
35
25
18
9
2
0
African Americans
123
68
50
35
24
18
14
10
8
5
5
3
2
1
1
0
stages I-II and III-IV. Similarly, in Caucasians, 5-year CSM rates were 32.9% and 75.4% in, respectively, ENSAT stages I-II and III-IV. Overall, 5-year OCM rates were 11.0% vs 9.5% in, respectively, African Americans and Caucasians.
Discussion
African American race/ethnicity represents a risk factor for higher stage and worse survival in several primaries. Worse socio-economic status and higher percentage of uninsured and less access to timely, appropriate, and
high-quality healthcare among ethnic minorities may explain racial related cancer inequalities (Cancer Facts & Figures for African American/Black People 2022- 2024, https//www.cancer.org, accessed on December 27, 2022). Among urological malignancies, Batai et al. found that African Americans with RCC were more likely to be diagnosed with advanced tumor stage compared to other races/ethnicities (odds ratio (OR): 6.51) (Batai et al. 2019). Stafford et al. relied on a historical cohort of RCC patients across all stages within a population- based cancer registry also focusing on incidence and
| Variables | HR (95% CI) | P-value |
|---|---|---|
| Race/ethnicity | ||
| African American vs Caucasian | 0.84 (0.62, 1.15) | 0.3 |
| Age at diagnosis (years) | 1.01 (0.99, 1.01) | 0.5 |
| Sex | ||
| Male vs female | 0.96 (0.75, 1.24) | 0.8 |
| Marital status | ||
| Unmarried vs married | 1.11 (0.87, 1.42) | 0.4 |
| Unknown vs married | 0.81 (0.46, 1.42) | 0.5 |
| Tumor grade | ||
| G3-4 vs G1-2 | 1.60 (0.78, 3.28) | 0.2 |
| GX vs G1-2 | 2.26 (1.33, 3.83) | <0.001 |
| ENSAT staging group | ||
| II vs I | 1.28 (0.67, 2.46) | 0.5 |
| III vs I | 2.68 (1.38, 5.19) | <0.001 |
| IV vs I | 4.19 (2.18, 8.05) | <0.001 |
| Type of treatment | ||
| Systemic therapy only vs none/unknown | 0.55 (0.36, 0.84) | 0.01 |
| Adrenalectomy only vs none/unknown | 0.31 (0.21, 0.48) | <0.001 |
| Adrenalectomy and systemic therapy vs none/unknown | 0.40 (0.27, 0.59) | <0.001 |
| Postoperative radiation therapy Administered vs not administered | 0.50 (0.32, 0.80) | <0.001 |
HR, hazard ratio; ENSAT, European Network for the Study of Adrenal Tumors. Values in bold indicate statistical significance set at P < 0.05.
A
Stage I-II
Stage III-IV
O
8
2
8
Rates
14
Rates
8
0
3
CSM: 31.2%
2
CSM: 75.3%
-
-
OCM: 13.3%
2
OCM: 9.8%
0
12
24
36
48
60
0
12
24
36
48
60
Months
Months
B
Stage I-II
Stage III-IV
8
8
2
2
Rates
:
Rates
3
3
8
8
8
D
9
CSM: 32.9% OCM: 8.3%
D
CSM: 75.4%
2
OCM: 10.7%
0
12
24
36
48
60
0
12
24
36
48
60
Months
Months
survival disparities among different racial/ethnic groups, demonstrating that African Americans exhibited higher incidence, lower age at presentation, and worse survival rates compared to other races/ethnicities (P < 0.001) (Stafford et al. 2008). These findings were also confirmed by Luzzago et al. who specifically focused on the metastatic setting, where African American race/ ethnicity was independently associated with a 1.2-fold higher mortality compared to Caucasian race/ethnicity in patients harboring clear cell histologic subtype (Luzzago et al. 2020). Similar evidence equally importantly apply to PCa and urothelial carcinoma. Li et al. relied on SEER (2004-2014) and found that incidence rates of distant stage PCa increased in recent years in African American patients (Li et al. 2018). In metastatic PCa, Würnschimmel et al. (2021) also demonstrated that African Americans were usually diagnosed at lower age and exhibited the least favorable survival profile compared to other races/ ethnicities (Würnschimmel et al. 2021). Finally, Sung et al. examined racial/ethnic differences in 72,452 bladder cancer patients across all stages, showing that African Americans presented more frequently with advanced tumor stage and higher tumor grade. African American race/ethnicity also represented an independent predictor for higher CSM in multivariable Cox regression analysis (HR: 1.30, P < 0.001) (Sung et al. 2019). Similar survival
findings were highlighted by Chierigo et al. who reported that African Americans harboring metastatic urothelial carcinoma of the urinary bladder exhibited the worst survival outcomes compared to Caucasians, Hispanics, and Asians (Chierigo et al. 2022).
Our research group recently focused on tumor characteristic distribution, treatment disparities, and differences in oncological outcomes between ACC patients of Hispanic and Caucasian race/ethnicity (Panunzio et al. 2022). However, the effect of African American race/ ethnicity on these endpoints in ACC is still unknown. We addressed this unmet need in the current study. We hypothesized that African Americans with ACC present with higher disease stage and grade, do not receive the same treatment and benefit of lower survival than their Caucasian counterparts. We tested these hypotheses within SEER. We made several noteworthy observations.
First, we only identified 1016 African Americans and Caucasian ACC patients within SEER. Of those 123 (12.1%) were African Americans and 893 (87.9%) were Caucasians. These individuals account for the vast majority of ACC patients within SEER. In previous reports addressing ACC demographics, 9-10% and 3-7% of patients were represented by Hispanics and Asians, respectively (Klaassen et al. 2015, Tella et al. 2018, Abdel- Rahman 2022). In consequence, approximately 150-200 additional individuals would have been included if our analyses focused on all ACC patients regardless of race/ ethnicity. Nonetheless, even with potential inclusion of Hispanics and Asians, the ACC cohort by all standards can be qualified as one depicting an orphan entity or at least a rare disease. Therefore, the use of large-scale database such as SEER or National Cancer Database (NCDB) is essential to investigate the effect of race/ ethnicity minorities in rare diseases.
Second, we did not identify clinically meaningful or statistically significant differences between African Americans and Caucasians, except for marital status. Specifically, no differences existed regarding tumor stage and grade as well as patient age. These findings reject the original hypothesis about less favorable stage and grade in African Americans with ACC, relative to Caucasians that originate from reports addressing other primaries (Stafford et al. 2008, Iqbal et al. 2015, Fuletra et al. 2018, Li et al. 2018, Varlotto et al. 2018, Sung et al. 2019, Luzzago et al. 2020, Wenzel et al. 2021).
Third, important differences existed regarding marital status. Specifically, African American ACC patients were more frequently unmarried than their Caucasian counterparts (56.9% vs 35.5%, P < 0.001). Marital status
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| Cancer |
is an important determinant of treatment type and survival in several primaries other than ACC (Goodwin et al. 1987, Abern et al. 2012, Sammon et al. 2012, Knipper et al. 2019, Rosiello et al. 2019, Ruvolo et al. 2021). For example, in metastatic RCC, Rosiello et al. found that unmarried patients were less likely to benefit from the same treatment intensity as married ones (Rosiello et al. 2019). Similarly, even for ACC, Klassen et al. observed that unmarried patients experienced a 1.3-fold increase in overall mortality (P=0.003), as well as a 1.3-fold increase in CSM (P=0.007) vs married patients. The survival disadvantage applied even after controlling for age, sex, pathological tumor characteristics, and type of treatment (Klaassen et al. 2015). In consequence, marital status represents a potentially important source of bias and requires the most complete adjustment and/or matching to maximally reduce its potentially confounding effect. Based on these concepts, we relied on PSM for marital status, as well as for all assessable variables, to provide the most unbiased illustration of the effect of African American race/ethnicity on CSM. Additionally, we applied multivariable adjustment for residual differences that persisted after matching. To the best of our knowledge, these methodological steps were not applied to any previous ACC analyses, regardless of their endpoint.
Fourth, the distribution of treatment modalities in African Americans virtually perfectly corresponded to those recorded in Caucasians. Specifically, no statistically significant differences were observed for adrenalectomy only, systemic therapy only, combination of both adrenalectomy and systemic therapy, and postoperative radiation therapy administration rates. In consequence, these findings reject the hypothesis that African Americans may not benefit from the same treatment as Caucasians. These observations disagree with a historical report of Hammad et al. who in a large series of ACC patients within NCDB (2004-2013) observed that African American race/ethnicity independently predicted lower rates of surgical management (OR: 0.68, P=0.012). This result was recorded even after controlling for demographic variables, socio-economic status, and pathological characteristics (Hammad et al. 2017). This may suggest that treatment barriers that existed historically no longer apply today.
Fifth, in analyses addressing the entire ACC population regardless of stage, 5-year CSM rates were, respectively, 58.5% and 57.9% in African Americans and Caucasians. The respective multivariable HR quantified after PSM revealed the absence of statistically significant differences (0.84 (P=0.3)), when African Americans were compared to Caucasians. Similarly, after stratification
according to ENSAT stages I-II vs III-IV groupings, virtually the same CSM rates emerged for African Americans (31.2% vs 75.3%) and Caucasians (32.9% vs 73.4%). Unfortunately, more detailed analyses focusing on individual ENSAT stages were not possible in the current study due to insufficient numbers of observations. Despite the absence of statistically significant association between African American race/ethnicity and worse prognosis in the current ACC patient cohort, the multivariable CRR models confirmed the importance of tumor stage and radical surgery among treatment options in predicting survival, as highlighted by international guidelines (Fassnacht et al. 2018). To the best of our knowledge, the current study represents the first formal test of the effect of race/ethnicity on CSM in ACC. However, other analyses with primary objectives that were different from CSM occasionally included race/ethnicity as a covariate. In those non-dedicated analyses, African American race/ ethnicity was not clearly associated with worse outcomes (Hammad et al. 2017, Wang et al. 2017, Tella et al. 2018, Zhang et al. 2020, Ginsburg et al. 2021, Stone et al. 2021). However, multiple methodological limitations apply to these interpretations. In consequence, the current study represents the only formal demonstration of lack of differences in CSM between African Americans and Caucasians, with other studies only providing partial evidence with suboptimal methodologies.
Finally, we also examined the contribution of OCM relative to CSM in ACC, according to race/ethnicity. Here, African Americans exhibited very similar OCM rates to those of Caucasians in the entire cohort (11.0% vs 10.1%). The similarities apply after stratification according to ENSAT stage I-II vs III-IV groupings. Specifically, in African Americans, 5-year OCM rates were 13.3% and 9.8% in, respectively, ENSAT stages I-II and III-IV vs 8.3% and 11.3% in Caucasians. To the best of our knowledge, we are the first to address OCM in ACC, in addition to being the first to address OCM in stage-specific and race/ethnicity- specific fashion. It is of interest that OCM rates did not exhibit large differences according to ENSAT I-II vs ENSAT III-IV stage groupings. In other primaries, higher OCM rates usually apply to stage I and II patients than to stage III and IV patients. Similarly, lower CSM rates usually apply to stage I-II patients than what was recorded in the current analyses addressing stage I-II ACC. Therefore, higher CSM than in other primaries may explain lower OCM than what is usually recorded in other primaries.
Several limitations need to be acknowledged. First, despite the large scale of the SEER database, the overall recorded number of ACC patients was relatively small.
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To compensate for sample size limitations, oversampling of race/ethnicities minorities might allow better powered future comparisons. Based on sample size limitations, stratification of outcomes according to ENSAT I vs II and ENSAT III vs IV stages groupings was not possible. Second, grade assignment in the SEER database does not reflect the World Health Organization grade assignment recommendations for ACC (Mete et al. 2022). Additionally, it should be noted that tumor grade was unavailable in 99 (80.5%) and 685 (76.7%) of African Americans and Caucasians, respectively. Nonetheless, in the current analysis, grade exhibited the expected association in both univariable and multivariable CRR analyses predicting CSM. In consequence, SEER grade was included in all multivariable models in the current study, as was the case in previous studies. Third, the SEER database does not provide information on genetics related to ACC (Petr & Else 2016) or potential prognostic factors other than ENSAT stage, such as Ki67 tumor expression, surgical margin status and endocrine tumor activity, which could have allowed a better stratification of patients cohort into more specific prognostic groups or a better balanced and unbiased comparison (Berruti et al. 2014, Beuschlein et al. 2015, Libé et al. 2015, Elhassan et al. 2021). Fourth, limited details regarding treatment type were available. Specifically, the SEER database does not provide additional information on potential cytoreduction in more advanced disease stages or on type, dose, and timing of systemic therapy and radiation therapy administration. Finally, other limitations related to the retrospective nature of the SEER apply to the current study as well as to other analyses based on similar large-scale databases.
Conclusions
Unlike in other malignancies, in ACC, African American race/ethnicity is not associated with higher tumor stage and grade at initial diagnosis. Additionally African Americans benefit from the same treatment type and intensity than Caucasians. Therefore, African American race/ethnicity is not associated with a survival disadvantage.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding
This work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
@ 2023 the author(s) Published by Bioscientifica Ltd. Printed in Great Britain
Data availability statement
All data generated for this analysis were from the SEER database. The code for the analyses will be made available upon request.
Ethics consent statement
All analyses and their reporting followed the SEER reporting guidelines. Due to the anonymously coded design of the SEER database, study-specific Institutional Review Board ethics approval was not required.
Author contribution statement
AP - conceptualization, methodology, formal analysis, writing original draft, writing review and editing, and visualization. ST, LH, CCG, MP, FB - writing review and editing and visualization. ZT - methodology, software, validation, formal analysis, and resources. AT, CT, AB, ODC, FC, FS, DT, SS, IB, MAC, and AA - writing review and editing and supervision. PK - writing review and editing, supervision, project administration, and conceptualization. All authors contributed to the article and approved the submitted version.
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Received 31 March 2023 Accepted 12 April 2023 Available online 12 April 2023 Version of Record published 2 June 2023
@ 2023 the author(s) Published by Bioscientifica Ltd. Printed in Great Britain