Racial comparison of patients undergoing minimally invasive partial nephrectomy for renal masses at a large volume tertiary center

Introduction and Objective: African American (AA) race has been identified to have a higher incidence of chronic kidney disease (CKD) and worse renal cancer survival compared with Caucasian Americans (CA), irrespective of tumor size, pathologic type, and surgical procedure. We aimed to compare the outcomes between CA and AA patients undergoing minimally invasive partial nephrectomy (PN) at our high-volume center. Materials and Methods: We queried our PN data repository from 2007 to 2017. We identified 981 cases of PN (robotic n = 943 and laparoscopic n = 38), of which there were 852 CA and 129 AA patients. We compared age, sex, body mass index (BMI), operative time, estimated blood loss (EBL), nephrometry score, tumor size, preand postoperative estimated glomerular filtration rate (eGFR), length of stay, Charlson Comorbidity Index (CCI), tumor characteristics, and 30-day complication rate. We then estimated the overall survival and disease-specific survival. Results: Age, BMI, operative time, EBL, nephrometry score, tumor size, CCI, length of stay, and sex were not statistically different. The mean preoperative eGFR was higher in the AA cohort (91.4 mL/min/1.73 m2 vs 86.1 mL/min/1.73 m2, p = 0.007); however, at 1 year, there was no mean difference (76.8 mL/min/1.73 m2 vs 74.5 mL/min/1.73 m2, p = 0.428). There was a higher percentage of Fuhrman Grade 3/4 in the AA cohort (33.3% vs 22.5%, p = 0.044). The AA cohort had a 2.66 × higher incidence of papillary renal cell carcinoma (RCC) (34.9% vs 13.1%, p < 0.001) and unclassified RCC (3.9% vs 0.4%, p = 0.001). There was no difference in tumor stage (p = 0.260) or incidence of benign histology (15.3% vs 11.6%, p = 0.278). There were no differences in 30-day complications (p = 0.330). The median follow-up was 43.2 months. By using Kaplan–Meier curves, there was no observed difference in overall survival (p = 0.752) or disease-free survival (p = 0.403). Conclusions: Our cohort of AA and CA patients with intermediate follow-up showed no worse outcomes for CKD or survival when undergoing laparoscopic or robotic PN. For low-stage renal cancer, there was no difference in overall survival and disease-free survival at a median follow-up of 43.2 months among AA patients, despite having higher grade tumors and a higher percentage of unclassified RCC. Our cohort of AA patients did have a higher incidence of papillary RCC. The equivalent overall survival and disease-free survival could be due to the earlier discovery of lower stage renal masses incidentally identified on imaging studies performed equally for other reasons in both AA and CA patients.


Introduction
Renal cell carcinoma (RCC) is one of the most common genitourinary malignancies. Tumors of the kidney and renal pelvis have an estimated 73,820 new cases in 2019 with 14,770 deaths. 1 Across specialties, the utilization of minimally invasive surgery has increased year over year when compared with more conventional open approaches. 2 In urologic surgery, partial nephrectomy (PN), active surveillance, and percutaneous thermal procedures have supplanted the traditional radical nephrectomy for management of small renal masses. PN has become a standard of care. This was bolstered by the 2017 American Urological Association (AUA) Renal Mass and Localized Renal Cancer Guideline. 3 The incidence of kidney tumors has increased since the 1970s in part due to incidental findings of small renal masses on imaging performed for a non-kidney cancer reason. 4 Despite improvement in widespread population outcomes with the adoption of this minimally invasive procedure, persistence of community disparities as shown by some studies demands further exploration into potential causes.
When it comes to comparing the African American (AA) and Caucasian American (CA) population, there are many confounding factors and many studies attempting to explain these discrepancies. AA patients have a higher incidence of kidney cancer (15.6/100,000) compared with CA patients (14.0/100,000). 5 According to DeSantis and colleagues, for most non-skin cancers, the AA population has the highest death rate and lowest survival rate compared with any other group. However, when investigating kidney tumors specifically, the death rates are reported to be similar to CA in recent studies. 6 In some epidemiological studies including a large California Cancer Registry/Surveillance, Epidemiology, and End Results (SEER) database analysis, the AA race has been identified to have a higher incidence of chronic kidney disease (CKD), higher incidence of RCC, and lower survival rate compared with CA, irrespective of tumor size, pathologic type, and surgical procedure. 7,8 Kiechle and coworkers reviewed the National Cancer Database of 118,207 patients with clinical T1a renal masses stratified by hospital characteristics. In their study, a greater proportion of CA patients (37.3%) underwent PN compared with AA (32.4%) and Hispanic patients (33.7%). 4 Many explanations for the etiology of these disparities have been posited including one study investigating deferred or delayed therapy related to access to care. 9 A recent study by Li and associates found that patients with insurance experienced improved cancer-specific survival compared with those with Medicaid and no insurance. 10 We aimed to retrospectively compare the outcomes of undergoing minimally invasive PN at our highvolume center in the Midwest region between AA and CA, with an AA patient population size in proportion with the U.S. national average for the AA race (11%-13%).

Materials and Methods
Our PN data repository is a retrospectively collected database and contains pre-, peri-, and postoperative data for patients treated for small renal mass at our institution from 2007 to 2017. We identified 981 PN cases, of which 943 were performed robotically and 38 laparoscopically. In our cohort, there were 852 CA and 129 AA patients. CA and AA cohorts were delineated by how the patient self-identified in the demographics component of our electronic medical record. We compared age, sex, body mass index (BMI), operative time, estimated blood loss (EBL), nephrometry score, tumor size, pre-and postoperative estimated glomerular filtration rate (eGFR), length of stay, Charlson Comorbidity Index (CCI), tumor stage, grade, tumor classification, and 30-day complication rate. We investigated for differences in insurance type and status at the time of surgical intervention between the two cohorts. We also estimated the overall survival and disease-specific survival. Institutional Review Board approval was obtained.

Statistical analyses
Wilcoxon rank-sum tests and chi-square tests of independence were used to determine statistical differences between CA and AA cohorts for quantitative variables and qualitative variables, respectively. Fisher's exact test was substituted for qualitative comparisons where there were five or less occurrences in either group. Kaplan-Meier survival curves using the log-rank test were used for time-to-event analysis and comparison of curves between CA and AA cohorts. Statistical significance was set to p < 0.05. All analyses were performed using R version 3.5.2. 11

Baseline characteristics
In our cohort, 13% of the patients were AA. Baseline characteristics are outlined in Table 1. The mean age in CA patients was 58.4 years and 58.3 years in AA patients. BMI was also similar between CA and AA cohorts (30.9 and 32.1 kg/m 2 , respectively). The mean clinical tumor size was equivalent at 3.0 cm in both groups. The mean preoperative eGFR favored the AA cohort 91.4 mL/min/1.73 m 2 compared with 86.1 mL/min/1.73 m 2 in the CA cohort. Patient sex distribution was no different between the groups. The proportion of patients having preoperative CKD was also not statistically different. CCI scores were compared between the two cohorts, and they were equivalent. T 1. B C ( The multivariate analysis of perioperative outcomes is shown in Table 2. Operative time, EBL, nephrometry score, tumor size, CCI, length of stay, and sex were not statistically different. The mean preoperative eGFR was higher in the AA cohort (91.4 mL/min/1.73 m 2 vs 86.1 mL/min/1.73 m 2 , p = 0.007); however, at 1-year, there was no mean difference (76.8 mL/min/1.73 m 2 vs 74.5 mL/min/1.73 m 2 , p = 0.428). There was no significant difference in the percent change in eGFR between the two cohorts (−10.8% vs −13.8%, p = 0.36). When breaking down eGFR into CKD stages preoperatively and postoperatively, there was a statistically significant difference; however, upon further investigation, this was skewed by two AA patients with eGFR <15 preoperatively and postoperatively. There was a higher percentage of Fuhrman Grade 3/4 in the AA cohort (33.3% vs 22.5%, p = 0.044). The AA cohort had a 2.66 × higher incidence of papillary RCC (34.9% vs 13.1%, p < 0.001) and unclassified RCC (3.9% vs 0.4%, p = 0.001). There was no difference between papillary RCC subclassifications as assigned by the pathologist (p = 0.667). There was no difference in tumor stage (p = 0.260) or incidence of benign histology (15.3% vs 11.6%, p = 0.278). The rate of positive surgical margins was not statistically different between the CA and AA cohorts (5.8% vs 4.7%, p = 0.953). Interestingly, we identified an unequal distribution of benign pathologies. Within the AA cohort, there was a higher incidence of angiomyolipoma (7.0% vs 3.9%, p < 0.001), and the CA cohort had an approximately twofold incidence of oncocytoma (10.4% vs 4.7%, p < 0.001). There were no differences in 30-day complications (p = 0.330). The median follow-up was 43.2 months (Table 3). Using Kaplan-Meier curves for patients with renal malignancy, there was no observed difference in overall survival (p = 0.752) or disease-free survival (p = 0.403) (Fig. 1).

Insurance status
There was no statistical difference between the insurance type and status of patients in our two cohorts at the time of surgical intervention. The most common insurance classification was Commercial, followed by Medicare. An equal number of patient's insurance status in each cohort was not captured by our database (18.3% CA vs 18.6% AA, p = 0.410) ( Table 4).

Discussion
With advancements in technology and surgical technique, minimally invasive PN has gradually transitioned into its role as a standard of care for small renal masses. Alongside this progression, the increased utility of imaging procedures (e.g., CT, ultrasound, MRI) has resulted in increased kidney cancer diagnosis, 4 of which incidence and mortality rates have been reported more pronounced among AA in  comparison to CA. 12 In the recent 2019 Cancer Statistics publication, the 5-year overall survival rate in CA was 93% in contrast to 91% in AA. It has been postulated that this discrepancy in life-expectancy may be attributable to factors such as tumor biology, 13,14 health care access, uninsured status, delayed treatment, and comorbidities such as obesity and hypertension. 9,15 Furthermore, it has been highlighted that functional outcomes after PN may also play a role in disease survival. For that reason, in this study, we aimed to compare the outcomes after PN between AA and CA patients. With regard to other genitourinary cancers, AA race is associated with worse outcomes. This is particularly evident in prostate cancer. As noted by Siegel and colleagues, this is strongly associated with lower socioeconomic status and barriers to health care access. Furthermore, when considering all cancers, incidence and mortality are higher among AA compared with other racial groups. Between 2011 and 2015, AA had a 9% higher incidence of overall cancers compared with CA. Fortunately, Siegel and colleagues reported that the overall cancer mortality disparity has decreased from 33% in 1993 to 14% in 2016 highlighting improvement in detection, treatment, and risk factor mitigation, particularly smoking. 1 In a recent matched analysis study conducted by Falagario and associates, it was reported that there was no significant difference in renal function, more specifically acute kidney injury and eGFR reduction, after robot-assisted partial nephrectomy (RAPN) between 63 AA and 936 CA patients. 16 Furthermore, a study by Kara and associates also reported no significant differences in kidney function outcomes in 84 AA in comparison to the CA group at 1 year follow-up. 17 In contrast to these findings, Wang and associates discovered a significantly lower postoperative eGFR among 105 AA patients in comparison to 212 CA patients after RAPN (50.59 mL/min vs 57.85 mL/min, p < 0.001). However, this series only compared preoperative, intraoperative, and postoperative factors among patients, while not accounting for the higher rates of diabetes mellitus and hypertension afflicting the AA population. 8 As such, we evaluated pre-, peri-, and postoperative factors including comorbidities at our large academic institution. Our analysis showed similar patient populations with regard to age, BMI, clinical tumor size, sex distribution, and CCI score. The eGFR in the AA group was found to be statistically significantly higher than that in the CA cohort preoperatively; however, postoperatively, there was no significant difference at 1-year follow-up. While the AA cohort had a mean absolute decrease in eGFR larger than their CA counterparts did, on multivariate analysis, the percent change in eGFR preoperatively and postoperatively at 1 year did not represent a statistically significant finding. In addition, it is worthy to note that the AA patients had a higher frequency of Fuhrman Grade 3/4 RCC and unclassified RCC on final pathology in contrast to their counterpart CA patients, yet our study showed that AA patients demonstrated no significant difference in overall survival and disease-free survival over a median follow-up of 43.2 months. This finding may be attributable to the fact that AA patients also exhibited a higher incidence of papillary RCC compared with CA patients, which has been determined to have a better prognosis than clear cell RCC by many studies. 18,19 Although there was a higher incidence of papillary RCC in the AA population, there was no statistical difference in the subtypes of papillary RCC between the two cohorts.
When comparing clinically localized as well as higher stage disease, it has been shown in several studies that AA patients present at a younger age. 9,20 AA patients with high-stage disease have poorer outcomes in disease-specific survival and overall survival. 21 In this study, our results highlight no significant differences among the functional and oncologic outcomes after PN between these two groups and suggest that the disparity in overall survival may portend to other factors such as genetic variability and tumor biology. 21 Furthermore, in an effort to evaluate socioeconomic factors impacting outcomes as suggested by Li and colleagues, we compared the two cohort's insurance type and status at the time of surgery. 10 Our analysis showed no statistical difference between CA and AA patients. This may reflect our focus as a large academic referral center on mitigating barriers to access.
An unanticipated finding in our analysis was an unequal distribution of benign pathologies. Our AA cohort had a higher incidence of angiomyolipoma compared with the CA cohort (7% vs 3.9%, p < 0.001), whereas the CA cohort had an approximately twofold incidence of oncocytoma (10.4% vs 4.7%, p < 0.001).
To the best of our knowledge, there is no racial predilection for angiomyolipoma including those related to tuberous sclerosis complex. The inequality in oncocytoma incidence is also not explained in the current literature. We believe that this is an interesting finding worthy of investigation in future studies.
Our analysis has some important limitations. Although our comparison of PN outcomes was congruent in racial distribution with the regional average, we did not delve into analyzing the rate at which AA and CA underwent alternative treatment modalities, such as active surveillance, radical nephrectomy, or ablation. This has been an important distinction in prior studies investigating access to health care and the disproportionately lower rate at which AA undergo PN compared with CA. 9,22,23 Additionally, in our intermediate follow-up study, we recognize the slow growing nature of papillary RCC, and with a longer monitoring horizon, we may see multifocality arise in some patients.

Conclusions
Our cohort of AA and CA patients with intermediate follow-up showed no worse outcomes for CKD or survival when undergoing laparoscopic or robotic PN. For low-stage renal cancer, there was no difference in overall survival and disease-free survival at a median follow-up of 43.2 months among AA patients, despite having higher grade tumors and a higher percentage of unclassified RCC. Our cohort of AA patients did have a higher incidence of papillary RCC. The equivalent overall survival and disease-free survival could be due to the earlier discovery of lower stage renal masses incidentally identified on imaging studies performed equally for other reasons in both AA and CA patients.