The Latinx Disparity in Surgery for Kidney Cancer: Data
from The South Texas Region
Furkan Dursun, MD,1 Rahul S. Patel, MS,1 Dawn S. Hui, MD,2 Hanzhang Wang, MD,1 Ahmed M. Mansour MD,1,3, Deepak K. Pruthi, MD,1,3, David G. Alonzo, MD4, Lalithapriya Jayakumar, MD5, Ronald Rodriguez, MD1,3, Robert S. Svatek, MD1,3, Michael A. Liss, MD1,3, and Dharam Kaushik, MD1,3
1. Department of Urology, University of Texas Health San Antonio, TX, USA
2. Department of Cardiothoracic Surgery, University of Texas Health San Antonio, TX, USA
3. University of Texas Health San Antonio/ MD Anderson Mays Cancer Center, TX, USA
4. Department of Urology, University of Texas Rio Grande Valley, TX, USA
5. Department of Surgery, Division of Vascular & Endovascular Surgery, University of Texas Health San Antonio, TX, USA
ABSTRACT
South Texas region, with a predominantly Latinx population, has a very
high incidence of renal cell carcinoma (RCC), including those with tumor extending
into the major blood vessels called venous tumor thrombus (VTT).
There is currently no data on outcomes of Latinx patients with VTT as most
published studies are from predominantly Caucasian population. Therefore,
we performed this study to fill an urgent, unmet need. We reviewed patients
who underwent radical nephrectomy with removal of VTT (called tumor
thrombectomy) between 2015 and 2020. We collected data on demographics,
clinical, pathological characteristics and outcomes of patients. Univariate
and multivariate Cox regression analyses were used to evaluate the associations
between ethnicity and disease progression or survival. We identified
112 patients, of which 67 (62%) were Latinx, and 41 (38%) were non-Latinx.
Approximately 60% of patients had Level II-IV VTT; Latinx presented with
a higher level of tumor thrombus (p=0.046). Latinx patients had a higher
rate of no insurance (11% vs. 27%, p=0.04) and were more likely being lost to
follow-up after surgery (22.4% vs. 13.3%, p=0.23) compared to non-Latinx.
Fewer Latinx received systemic therapy (28% vs. 42%; p=0.13). Ninety-day
mortality for the entire cohort was 3.8%. The Latinx population in the South
Texas region present late, with advanced thrombus level, and do not have
access to systemic therapy. Given symptomatic disease, surgical treatment,
if feasible, is their only option. Our results highlight disparate treatment patterns
which require further investigation and health-care policy changes.
INTRODUCTION
Kidney cancer is the 8th most
common malignancy in the
United States with an estimated
73,750 new cases and approximately
15,000 mortalities in 2020.1
Renal cell carcinoma (RCC) has a
tendency for vascular invasion: 10-
15% of patients have venous tumor
thrombus (VTT) and 1-3% of cases
have tumor thrombus extending into
the right atrium. 2,3 Inferior vena
cava involvement or obstruction by
tumor thrombus can produce various
clinical manifestations, including
gross hematuria, lower extremity
edema, varicocele, abdominal
distension with hepatic dysfunction
(possibly related to a Budd-Chiari
syndrome), fatigue, malabsorption,
shortness of breath, and pulmonary
emboli. 4
Even in the era of targeted
therapy and subsequent immune
checkpoint inhibitors, radical
nephrectomy (RN) with tumor
thrombectomy remains the mainstay
of treatment for RCC patients with
VTT. This aggressive surgery has
significant morbidity and mortality,
but the 5-year survival rates can be
significant as up to 70%, especially
for patients without metastatic
disease. 5
Contemporary management
of RCC with VTT requires an
interdisciplinary approach and
resources to provide the best curative to palliative care, which
is mostly available in tertiary
care centers. Unfortunately, racial
disparities exist both in the access
to health care and the quality of care
administered in the U.S.6,7 Most of
racial disparity studies have focused
on differences between African
Americans and non-Latinx Whites
(NLW), there is paucity of data in
RCC regarding disparities in care
among the Latinx population, which
is the largest minority with 18.5% of
the total U.S. population. 8
With a predominantly Latinx
population, the South Texas region
has a very high incidence of RCC,
including those with VTT. 9 Of all
the South Texas Latinx, 31-61% are
uninsured.10 This disparity results in
delayed presentation of patients with
RCC. However, there is a paucity of
data on outcomes of Latinx patients
who underwent extirpative surgery
for their symptomatic disease.
Since most published literature
on tumor thrombus patients is
in the predominantly Caucasian
population with insurance, we
performed this study to evaluate
disparities between Latinx and
non-Latinx with RCC and VTT in
South Texas region. Our institution
is a tertiary referral center with
a catchment area of 2.5 million.
We are uniquely positioned as we
accept all South Texas patients for
surgical services, regardless of their
insurance status.
METHODS
Patient Selection
After approval by the Institutional
Research Ethics Board (IRB number:
HSC2021108E), we reviewed the
medical records of our prospectively
maintained database of patients
who underwent RN with tumor
thrombectomy for RCC between
2015 and 2020 at our institution.
Covariates
We abstracted patient-level
characteristics including age at
diagnosis, sex, ethnicity, body
mass index (BMI), American
Society of Anesthesiologists
(ASA) classification, smoking
status, insurance status, and
comorbidities such as diabetes
mellitus (DM), hypertension
and hypercholesterolemia.
Socioeconomic variables including
annual household income,
education level and distance from
home to hospital were estimated
from county of residence by using
patients’ self-reported zip code.
Ethnicity and race were determined
by patient self-report on their
electronic medical records (EPIC).
Disease characteristics included
clinical TNM stage, 11 thrombus
level, maximum clinical tumor size
and preoperative lab values. Mayo
Clinic RCC tumor thrombus level
classification system was used for
thrombus level. 12
Operative data included total
surgical time, surgical approach and
incision type, type of bypass, use
of intraoperative transesophageal echocardiography (TEE),
utilization of liver mobilization
or Pringle maneuver, resection of
IVC, estimated blood loss (EBL),
blood transfusion during surgery,
and perioperative complications.
Pathological characteristics of
the tumor were collected from
the pathology report. Early
postoperative complications (< 90
days) were classified according to the
Clavien-Dindo classification system.
30-day readmission rates, 90-day
mortality rate, patient follow-up
data including local recurrence,
disease progression, and survival,
as well as receipt of neoadjuvant
or adjuvant chemotherapy, were
recorded. Progression of disease was
classified as attenuated (not until
at least 6 months after surgery) or
rapid (progression or death within 6
months of surgery).
Statistical Analysis
The associations between
ethnicity (Latinx or Non-Latinx)
and demographic or clinical
characteristics were assessed
with Fisher’s exact test and the
two-sample Wilcoxon rank-sum
test for continuous variables. Chi square
test was used for assessing
categorical variables. Univariate
and multivariate Cox regression
models were used to evaluate the
associations between ethnicity and
disease progression or survival.
Significance was set at 0.05 and all
p values were two-tailed. Statistics
was performed using STATA 15.0
(StataCorp, College Station, Texas).
RESULTS
We identified a total of 112 patients
with bulky advanced RCC and VTT
who underwent RN and tumor
thrombectomy, including 67 (60%)
Latinx and 45 (40%) non-Latinx
patients. There were no significant
differences observed between
Latinxs and non-Latinx across
age, sex, accompanying chronic
conditions, ASA classification and
BMI (Table 1). Most of the patients
were male (70%) and more than
half were obese with a median BMI
of 30.8 (IQR 26-33.8). All but one
patient was classified as ASA III (56%)
or IV (43%). They had accompanying
chronic conditions such as diabetes
mellitus (44%), hypertension (65%),
and hypercholesterolemia (32%). 15%
of patients were active smokers. More
than three-quarters (78%) of the
patients had at least one complaint of
constitutional symptoms; weight loss
(41%), gross hematuria (47%), and/or
flank pain (42%).
Latinx patients had
significantly higher rate of no
insurance compared to non-Latinx
(26.9% vs. 11.1%, p=0.04). There was
no significant difference for distance
from home to hospital between
Latinx and non-Latinx (54 miles
Vs. 51 miles, p=0.79). The Latinx
population had significantly lower
annual income (p<0.001) and rate of
high school graduation (p<0.001).
Clinical and Perioperative Features
The median clinical maximum tumor
length at presentation was 96 mm
(IQR 74-123). Thirty two percent of
the patients presented with clinical
node positive disease and 25 %
with metastatic disease. Sixty-seven
(60%) patients had level II-IV tumor
thrombus indicating advanced
disease. Sixty-two (55%) patients
had right-sided tumors, which were
more likely to present with level III
or IV tumor thrombus than leftsided
tumors (40% vs. 24%; p=0.07).
Latinx presented with higher level
of tumor thrombus (p=0.046). Level
II-IV thrombus was seen in 67% of
Latinx vs 50% of non-Latinx (Table
1).
The median operation time
was 340 minutes (IQR 251-432).
The median EBL was 1000 ml (IQR
500-2375) and the median blood
transfusion during the surgery
was 555ml (IQR 0-1330). There
were significant increases in the
EBL during surgery as the tumor
thrombus level increased (p=0.003).
There was also an increasing trend
in the amount of blood given during
surgery as the tumor thrombus level
increased(p=0.08). Table 2 lists the differences
observed between Latinx and
non-Latinx across intraoperative
features, perioperative
complications, 30-day readmission
date and 90-day mortality. Latinx
patients, due to the high rate of level
II-IV tumor thrombus, indicating
advanced disease burden, were more
likely to have a thoracoabdominal
incision compared to non-Latinx
(15% vs. 5% p=0.21). Also, Latinx
underwent more complex surgical
maneuvers such as complete hepatic
mobilization during surgery than
non-Latinx (63% vs. 41%, p=0.03).
The radical nephrectomy was done
for cytoreductive purposes for 27%
of the patients, and retroperitoneal
lymph node dissection was utilized
for 66% of the patients. Given
advanced disease states, 60% had
intraoperative TEE to evaluate in
real time the level of thrombus
during the surgery.
The 90-day surgical
complications are summarized by
tumor thrombus level and ethnicity
in Table 3. One patient died during the
surgery and three patients died in the
postoperative 90 days (2.7%), with a
total perioperative mortality of 3.6%.
The median length of hospital stay
was six (IQR 4-10) days. There was
no statistically significant difference
in the duration of hospitalization
by tumor thrombus level (p=0.11)
or by ethnicity (p=0.06). 30-day
readmission rate was 9% and there
was no statistically significant
difference in the readmission rate
by thrombus level (p=0.56) or by
ethnicity (p=0.37).
Tumor Histopathology and
Survival Outcomes
The median tumor volume was
426 cm3 (IQR 246-933) on the
pathological evaluation. Fourteen
(12.5%) patients had regional
lymph node involvement, and
seven patients (6.3%) had a positive
surgical margin. Among 112 patients
evaluated, 102 (91.1%) had clear cell
RCC, and 7 (6.3%) had papillary RCC.
There was no significant difference
in the tumor histology by ethnicity
(p=0.58). Pathologic features are
listed in Table 4. More than 70%
of the patients were marked as
grade 3 or 4 within the Fuhrman
grading system- an indicator of very
aggressive cancer. Additionally,
63.1% of the patients had
histological tumor necrosis, 13.4%
had sarcomatoid differentiation, 17%
had rhabdoid differentiation, and
6.3% had translocation carcinoma.
Latinx patients had higher incidence
of very aggressive variant of RCC
called translocation carcinoma:
seven patients were reported with
translocation renal cell carcinoma,
and all of them were Latinx (p=0.03).
The median follow-up time
was 453 days (IQR 129-1125). The
Latinx was more likely had no
postoperative follow-up compare
to non-Latinx. (22.4% vs. 13.3%,
p=0.23). There were no significant
differences in 2-year and 3-year
survival for Latinx and Non-Latinx
patients (82% vs 83%, and 75% vs 77%, respectively, p=0.81 and 0.98).
Forty-eight patients (43%) had
progression, and twenty-one (18.8%)
patients died of advanced RCC.
Patients with higher Fuhrman grade
were more likely to have disease
progression (HR=2.08 p=0.001).
Of those patients with metastatic
disease, 33% received systemic
therapy. We observed less utilization
of systemic therapy in the Latinx
group compared to the non Latinx
group (28% vs. 42%; p=0.13). There
were no statistically significant
differences in 2- and 3-year survival
rates when compared patients with
level 0-II tumor thrombus and
patients with level III-IV tumor
thrombus (2- year survival: 83% -
79% p= 0.687, and 3-year survival:
76% - 74% p=0.454, respectively).
In the multivariate cox regression
model adjusted for thrombus level,
clinic stage, age, BMI, gender; the
ethnicity was not found to be a
significant prognostic factor for
disease progression and survival
(HR 0.75, CI 0.36–1.58, p= 0.45
and HR 0.9, CI 0.32–2.51, p= 0.84
respectively) (Table 5).
DISCUSSION
Texas is home to approximately
19% of Latinx population in the US,
majority of which are concentrated
in the South Texas region. Since
kidney cancer is the 4th leading
cause of death among Latinx males,
we attempted to study the disparity
and variation in a highly complex
presentation- kidney cancer with
tumor thrombus. The idea behind
performing this study was to
understand disparities to make
system-based changes. Our goal was
to twofold: to identify the disparity
in presentation of advanced kidney
cancer and identify differences
in quality of care exist between
Latinx and non-Latinx undergoing
radical nephrectomy with tumor
thrombectomy. In addition, we
sought to share our experience
with this challenging, high-risk
procedure in a predominantly
Latinx cohort. In this high volume,
single-institution, retrospective
study, we found that the Latinx in
the South Texas region presented
late, with advanced thrombus
level (67% vs. 50%, p=0.046). The
uninsurance rate was significantly
higher in Latinx than non-Latinx
(11% vs. 27% p=0.04), impacting the
number of patients lost to followup
and receiving systemic therapy.
Our results highlight disparate
treatment patterns across patients.
Despite delayed presentation, our
study shows that rapid coordination
of extirpative surgery enhances the
outcome for these patients with
equivalent perioperative outcomes.
Latinx is the largest and
youngest racial/ethnic minority
group in the US and rapidly
increasing in population size which
is expected to be doubled over the
next four decades.1 Unlike non-
Latinx, cancer is the leading cause
of death among Latinx, even though
the cancer incidence is not higher
than non-Latinx.14 Latinx are more
likely to present with an advanced
disease which partly contributes to
higher mortality rates, especially for
colorectal, endometrial, liver, and
stomach cancers.15 The incidence
and mortality of kidney cancer for
Latinx living in the US is similar to
all US populations.1 But the incidence
of kidney cancer in Texas, especially
in South Texas, is higher than in the
U.S., with Latinx significantly having
the highest incidence.9 Two recent
population-based studies reported
data on racial disparities in RCC.
Callahan et al. assessed the reasons
for the incidence disparity of RCC
in African Americans and Whites,
but Latinx were not evaluated
in this study.16 They reported
that interventions that prevent
hypertension and chronic kidney
disease among African Americans
could potentially eliminate the
racial disparity in RCC incidence.16
Utilizing the SEER database,
Whitson et al. evaluated the
prognostic factors of RCC patients
with VTT, and they reported race
was not associated with mortality
(HR 1.2 CI 0.5–2.9, p=0.63).17 Race
or ethnicity was not reported in
the prior case series for RCC and
VTT. 18-21 Our study is unique,
evaluating the disparities in patient
presentation, treatment approaches,
and outcomes for Latinx and Non-
Latinx patients with RCC and VTT. It
provides a contemporary real world
scenario from South Texas- a region
with very high incidence of kidney
cancer, low insurance, diverse
cultural and ethnic background.
RN with tumor
thrombectomy has proven long-term
disease-free survival, especially for
patients with the non-metastatic
disease.22, 23, 18, 20 The clear cell
carcinoma is the predominant
histology reported, changing
between 70 to 93% in different case
series.19, 20, 21, 24 Neither thrombus
level nor histological type was
associated with progression and
survival.18-24 Likewise, most of our
cases were clear cell RCCs (91%) and
the histologic type and thrombus
level were not associated with
disease progression or survival.
Surgical management
of RCC with VTT is challenging
and requires multidisciplinary
perioperative care. The surgical
approach may involve full liver
mobilization and thoracotomy to
allow access to the intrahepatic and
intrapericardial tumor thrombus
especially for patients with level
II-IV VTT. The intraoperative and
postoperative death in 30 or 90 days
was reported between 2.9 - 6.1%
in the largest series.18-21, 25 In the
same series with available data, the
perioperative death rate for level
III-IV tumor thrombus patients
was reported between 5.6-14.6%.18-
20, 24 Similar to those studies, the
perioperative death rates of our
cohort and for the subgroup of
patients with level III-IV tumor
thrombus was 3.6% and 8.1%,
respectively.
Xp11.2 translocation
RCC is caused by increased
expression of transcription factor
for immunoglobulin heavy chain
enhancer 3 (TFE3) as a result of
translocation of the TFE3 gene
on chromosome Xp11.2. It mainly
occurs in children and young adults,
accounting for 20-40% of RCC cases
in children. The incidence is low in
adults accounting for approximately
1% of RCC and there are only 7 cases
reported over the age of 65 years.26,27
The prognosis is less aggressive in
children and adolescents, but shows
poor prognosis in adults.28 Because
of the rarity, our understanding of
its pathogenesis is incomplete and
there is no data about the ethnic
differences in the incidence of Xp11.2
translocation RCC. We reported
7 patients with translocation
carcinoma and all of them were
Latinx (p=0.03) with a median age
of 50 years (range 21 to 67). Latinx
patients had higher incidence of this
aggressive variant of RCC which
needs further investigation.
This study has several
limitations. Foremost, this
retrospective single-institution
study is limited by inherent biases
in patient selection, data collection,
and analysis. The utilization of
preoperative embolization, lymph
node dissection, bypass, and
surgical approach was based on
the surgeon's clinical judgment and
experience which may be a source of
additional bias. The generalizability
of our results is limited due to
the high Latinx population in the
South Texas region. However, the
fundamental strength of this study
lies in the analysis of a large sample
size. To our knowledge, this is the
first study assessing disparities in
the presentation and quality of care
between Latinx and non-Latinx
RCC patients with venous tumor
thrombus.
In conclusion, compared to
Non-Latinx, the Latinx population
in the South Texas region presents
late, with advanced thrombus level,
and does not have access to systemic
therapy. Surgical treatment, if
feasible, is their only option. Our
results highlight disparate treatment
patterns. A better understanding of
the factors that cause such a high
rate of uninsurance in the Latinx is
crucial to creating more appropriate
and effective reform strategies.
FUNDING
None
AUTHOR CONTRIBUTION
DK planned the concept of the study
and DK, FD planned the study design.
FD, RP, and DK collected and verified
the data. HW analyzed the data and DK,
FD, RR and HW were involved in data
interpretation. FD and RP wrote the
first version of the manuscript. FD, RP,
DH, HW, AM, DP, DA, LJ, RR, RS, ML
and DK contributed to interpretation
of the results and revision of the
manuscript and approved the final
version of the manuscript. Project
administration was conducted by DK.
Declaration of competing
interests
The authors have no conflicts of
interest.
ACKNOWLEDGEMENTS
Furkan Dursun has received research
support through the University of Texas
Health Science Center at San Antonio
Cancer Research Training Program
supported by the CPRIT Research
Training Award (RTA; RP170345).
Dharam Kaushik is supported by
Stanley and Sandra Rosenberg
Endowment in Urologic Research
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Correspondence to: Dharam Kaushik M.D.
Department of Urology, University of Texas Health, San Antonio, TX 78229-3900.
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