








































This is an open access article under the terms of a license that permits non-commercial use, provided the original work is properly cited.  
© 2023 The Authors. Société Internationale d'Urologie Journal, published by the Société Internationale d'Urologie, Canada.

Key Words Competing Interests Article Information

LARCG,Latin America, renal cell carcinoma, 
international collaboration

None declared. Received on June 7, 2022 
Accepted on September 5, 2022 
This article has been peer reviewed.

Soc Int Urol J. 2023;4(1):27–33

DOI: 10.48083/GWSK7789

The LARCG Latin American Renal Cancer Group: 
Achievements in Support, Teaching, Research, 
Collaboration, and Advocacy

Stenio de Cássio Zequi,1,2,3 Francisco Rodriguez-Covarrubias,4 Ignacio Pablo Tobia,5 Alberto Jurado,5 
Anamaria Autran Gomez,6 Luiz Meza-Montoya,7 Walter Henriques da Costa,1,2 Alejandro Nolazco,8 
Thiago Camelo Mourao,9 Diego Abreu10

1 Department of Urology A.C. Camargo Cancer Center, São Paulo, Brazil 2 National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation,  
A.C. Camargo Cancer Center, São Paulo, Brazil 3 Graduate School-Urology-Escola Paulista de Medicina-Universidade Federal de São Paulo 4 Instituto Nacional de 
Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico 5 Hospital Italiano, Buenos Aires, Argentina 6 Lyx Institute of Urology. Madrid, Spain  
7 Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru 8 Hospital Británico, Buenos Aires, Argentina 9 Graduate School-Antonio Prudente Foundation,  
A.C. Camargo Cancer Center 10 Hospital Pasteur, Montevideo, Uruguay

Abstract

The Latin American Renal Cancer Group (LARCG) was founded in 2013. This is a non-profit collaborative group 
designed to foster scientific knowledge in all areas of kidney cancer, and to establish international cooperation among 
well-recognized oncologic institutions. Since its creation, LARCG has reported data from Latin America to the 
scientific community and has promoted accredited information and advocacy principles for patients, lay people, and 
medical colleagues. Currently, it consists of 44 centers in 7 Latin American countries and Spain. In this paper, we 
report our achievements in assistance, teaching, research, and advocacy, and we discuss the successful international 
collaborations.

Introduction

We created the LARCG (Latin American Renal Cancer Group) in 2013 to address the paucity of renal cell carcinoma 
(RCC) data in Latin America when compared with North America and Europe and to address the differences between 
the regions with respect to ethnic composition and health care systems[1]. LARCG is a non-profit collaborative group 
designed to foster scientific knowledge in all areas of kidney cancer, to produce high-quality scientific information, to 
establish international cooperation with well-recognized oncological institutions, to report data from Latin America 
to the scientific community, and to promote accredited information and advocacy principles to patients, lay people, 
and medical colleagues.

Since its creation, LARCG has grown and incorporated more centers, expanding its activities in several scenarios, 
in ways unusual for Latin America. In this manuscript, we aimed to report our achievements, divided by subtopics, 
discussing our future activities.

Creation, Expansion, and Economical Support of the Group and Our Database
The LARCG group was created by urologists, under the guidance of a specific statute. Our board has scientific, 
ethics, and economic committees. In each participating institution, LARCG is led by a local urologist, who invites 
other urologists, pathologists, medical oncologists, and radiologists to integrate their institutional departments into 

27SIUJ.ORG SIUJ  •  Volume 4, Number 1  •  January 2023

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mailto:steniozequi%40gmail.com?subject=
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LARCG’s branches of pathological anatomy, medical 
oncology, and imaging, respectively[1].

Soon after our foundation in 2014, we invited selected 
key opinion leaders from recognized high-quality 
urologic oncology centers in Central and South Amer-
ica, and Spain. Within a few weeks, 26 centers had joined 
the group. Retrospectively, we developed a compre-
hensive encrypted database containing more than 150 
variables, with demographic, clinical, and pathological 
information, therapeutic modalities, and oncological 
and functional outcomes of 4502 RCC patients from 22 
Latin American and 2 Spanish institutions.

In November 2014, we presented the results of our 
survival analysis of 4238 patients at the plenary session 
of the Confederación Americana de Urologia meet-
ing in Punta Del Este, Uruguay[1,2]. Between 2014 and 
2016, the group expanded to its current composition  
(44 centers from Argentina, Brazil, Bolivia, Chile, 
Mexico, Peru, Spain, and Uruguay). At the same time, 
we developed a bilingual (English/Spanish) website 
(available at https://larcg.org)[3].

During 2014, data of patients treated since 1980 were 
retrospectively entered by each participating institution. 
Subsequently, information was received about patients 
treated until 2016, resulting in more than 6000 cases.

The inclusion criteria for participation in the LARCG 
group were first, to accept the invitation, with the 
commitment to send the required information and the 
promise to follow our statute rules.

We sought to enhance the quality of our database, 
removing the repeated cases, searching information for 
missing values, and starting the development of a free, 
secure, and encrypted database in the Research Elec-
tronic Data Capture (RED Cap) (Vanderbilt University)
[4]. Only centers that adhered to these security database 
policies were accepted.

In the third—and current—phase, launched in 2020, 
we have received new cases from Chile, and we are also 
accepting prospective information. Concurrently, we 

are updating the original database, requiring follow-up 
information from each center, and encouraging them to 
include new cases.

The chronological flow presenting the expansion of 
our database and the diagram of its current structure are 
represented in Figures 1 and 2, respectively.

In May 2015, we presented our epidemiological data 
and administrative information at the SWOG fall meet-
ing in San Francisco, California. This was a key event to 
increase our networking with urologic oncology leaders, 
resulting in some scientific collaborations[1,5].

Up to 2014, we had no sponsorship from industry, and 
all efforts to create the LARCG were voluntary (unpaid). 
In 2016, the LARCG Project was classified as a strategic 
initiative by the A.C. Camargo Cancer Center (ACCCC), 
Brazil, and encompassed in a comprehensive project 
entitled INCITO-INOTE (Instituto Nacional de Ciên-
cia e Tecnologia em Oncogenômica e Inovação Terapêu-
tica) (National Institute for Therapeutic Innovation and 
Oncogenetics), founded by several official governmental 
and private Brazilian funding agencies, which support 
cancer research in that hospital[6].

The funds provided by the INCITO/INOTE project 
have covered the costs of our basic and translational 
investigations, as well as the acquisition of immunohis-
tochemistry reagents, biomolecular analyses, and labo-
ratory supplies. Additionally, we received funds from 
INCITO/INOTE for the maintenance of our website, for 
the payment of audiovisual resources used during the 
LARCG annual meetings at American Urological Asso-
ciation meetings[3,7]. These funds also covered travel 
expenses to bring international speakers to our Brazilian 
events, promoted by ACCCC. These funds are in place 
until 2023, when new applications will be made to the 
official funding agencies.

Other meetings were promoted by the LARCG 
group. They occurred at Hospital Pasteur (Montevi-
deo, Uruguay) and Hospital Británico (Buenos Aires, 
Argentina), and an advocacy event took place in Mexico 
City, funded by Asociación Ale[1]. These meetings were 
supported by each regional promoter center. The Kidney 
Cancer Association supported the expenses of the 
authors D.A. and S.C.Z. at the 17th and the 18th Kidney 
Cancer Symposiums, respectively[8].

In 2021, the Uruguayan LARCG team established the 
LARCG Foundation in that country. It is a non-profit 
virtual organization that received economic resources 
from the pharmaceutical industry (Roche Company) 
to cover database maintenance and the data managers’ 
salaries. This regional foundation receives donations for 
scientific initiatives through our website[3].

Abbreviations 
ACCCC A.C. Camargo Cancer Center
ASA American Society of Anesthesiologists
ccRCC clear cell RCC
EPO erythropoietin
IHC immunohistochemical
LARCG Latin American Renal Cancer Group
OS overall survival
RCC renal cell carcinoma
REN renin

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Finally, we reiterate that the LARCG members have 
received no salaries or professional fees for any of their 
activities. In collaborative studies among the centers, 
each center must cover its expenses.

Research
Prognostic factors: clinical markers
In the search of prognostic clinical markers in RCC, we 
evaluated patients with localized or locally advanced 
RCC, and patients with metastatic disease, reporting the 
prognostic factors in patients from Latin America.

In a survival analysis of 5670 patients with non-met-
astatic disease, using a multiple data imputation 
method to compensate for the effect of missing values, 
we demonstrated that the American Society of Anes-
thesiologists (ASA) classification ≥ 3 and the perirenal 
fat invasion, aside from other well-known factors, were 
independent predictors for worse overall survival (OS). 
Perirenal fat invasion and microvascular invasion were 
adverse prognostic factors for cancer-specific survival 
(CSS)[9]. In 2010, we published a study showing that 
patients with ASA classification ≥  3 presented more 
symptomatic tumors, higher nuclear grade, and larger 
lesions, besides of 10 times more metastasis than ASA 1, 
and the double those ASA 2. In the multivariable analy-

sis, ASA classification was an independent predictor of 
OS for the whole cohort, and CSS for the patients with 
non-metastatic RCC[10].

The ASA classification takes account the comorbid-
ities of the patients, which is not incorporated in the 
most used performance status classification in oncol-
ogy. As RCC is a metabolic disease[11], it seems logical 
that comorbidities could influence the outcomes of RCC 
patients. Additionally, ASA classification is a classifi-
cation recognized worldwide that can be validated in 
many institutions, without the potential biases related to 
the assistant surgeons.

In a series of 1523 small renal masses, we reported 
that ASA ≥ 3, bilateral tumors, and extracapsular inva-
sion were adverse independent prognostic factors for 
disease recurrence and metastases. In this study, patients 
≥ 65 had a better 10-year OS if they underwent partial 
nephrectomy rather than radical nephrectomy[12]. 
With respect to age, these results are in accordance with 
those of the Mexican LARCG team, which evaluated 410 
patients who underwent surgery. They demonstrated 
that patients > 75 years presented outcomes similar to 
those of their younger counterparts[13]. According to 
these series, we can verify that Latin American coun-

2020–22
After the COVID-19

pandemic:
New data acquisition,

and update of data
in each center

are in the progress

2015–2017
2nd round 

44 Centers / 8 Countries
n = 6132

Valid cases for survival
analysis; n = 4508

May 2015
2nd round of

invitations to the
centers

November 2014
1st round

24 Centers / 5 Countries
n = 4502

Valid cases for survival
analysis; n = 3819

Excel/SPSS 
�le database

Excel/SPSS 
�le database

2019 – 2020
Accreditation of 
the centers in the

new database

May 2019
Development of eCRF

(electronic Case 
Report Form)/REDCap

Review of data
quality, and data 

manager contracting

2018
Convocations

for migration to a 
secure, high-quality

database

January 2014
1st round 

of invitations
Six-month deadline
to input the dataset

May 2013
LARCG Foundation
Database creation

Brazil/Uruguay
with dozens of

variables

FIGURE 1.  
Chronological diagram for the expansion of the LARCG database 

29SIUJ.ORG SIUJ  •  Volume 4, Number 1  •  January 2023

The LARCG Latin American Renal Cancer Group: Achievements in Support, Teaching, Research, Collaboration, and Advocacy

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tries are progressively increasing their rates of mini-
mally invasive nephron-sparing surgeries, resulting in 
inherent benefits, such as reduced length of hospital stay, 
reduced bleeding and transfusion rates, and reduced 
pain or use of analgesics, as well as an earlier return to 
daily routine.

In an Argentinian series of 293 patients, the concom-
itant invasion of perirenal fat and renal sinus invasion 
was associated with an unfavorable setting for pT3a 
tumors. This is associated with higher mortality rates, 
venous involvement, and metastatic progression[14]. 
This study suggests a need for a subdivision of T3 stage, 
indicating that the concomitant fat and venous invasion 
present an ominous prognosis in comparison with any 
of these factors in isolation[15].

Recently, the Uruguayan LARCG team, in collabo-
ration with several recognized global experts in RCC, 
published their prognostic score in 530 de novo meta-
static patients. It was a unique database, since 511 
patients underwent nephrectomy, probably consisting 
of those in the more favorable risk group. In this series, 
the ASA classification ≥ 3, perirenal fat invasion, and 
more than 2 metastatic lesions were associated with 
poor 5-year OS and CSS. The authors presented a prog-
nostic score, ranging from 0 to 3 points, being: 0 point: 
favorable group; 1 point: intermediary group; and 2 or  
3 points: unfavorable group, which achieved the follow-
ing median survivals: not reached, 33 months, and 14 
months, respectively. In this population, patients with 
bone metastases, particularly those with non-vertebral 
lesions had better OS. These data deserve further inves-
tigation[16].

Validating the ASA classification, perirenal fat inva-
sion, and bone metastases as prognostic factors in other 
populations would be interesting and valuable, in order 
to extend resources in these areas.

2020–2022
Return to each center  of 

their original databases  and 
request for correction, updating,

and expansion of the data

May 2019
Development of
eCRF (Electronic

Case Report Form/
REDCap

LARCG
database of�ce & Central

database master
administrators 

Institutional database
administrators

Updated and corrected
original dataset

Imputation of 
new cases LARCG Centers

Immunochemistry markers
A project called LARCG 001 was launched, encompassing 
the analyses of several potential immunohistochemical 
(IHC) markers associated with “endocrine kidney 
enzymes” and with chromatin remodeling genes. 
We demonstrated that the low IHC expression of 
erythropoietin (EPO) was an independent adverse 
prognostic factor for OS and disease-free survival (DFS) 
in 220 patients with localized or locally advanced RCC 
(all histological types included)[17]. Furthermore, the 
lack of renin (REN) expression was an independent 
prognostic factor for DFS, with almost 3 times more 
recurrences than those expressing REN. This study 
analyzed 498 patients with non-metastatic clear cell 
RCC (ccRCC), in collaboration with the University 
of California Davis (UCD)[18]. In both studies, low 
expression of EPO or R EN was associated with 
unfavorable pathological features, such as higher 
TNM stages, higher nuclear grades, and larger lesions. 
The area of renal endocrine markers in RCC has been 
insufficiently studied enough and could open a new 
route of research. We are currently analyzing the 
concomitant expression of REN, EPO, and cathepsin D, 
an alternative renin-angiotensin pathway activator, in 
more than 700 patients (data not published).

Motivated by the new era of check-point inhibitors 
in RCC, we investigated the prognostic role of the IHC 
expression of the check-point markers (PD-L1 and PD-1) 
in collaboration with Lee Moffitt Cancer Center (Tampa, 
FL). In a series of 1017 patients with non-metastatic 
ccRCC (follow-up data available in 738 cases), the higher 
expression of these markers was associated with higher 
tumor stages, intratumoral necrosis, and lymph-vascu-
lar invasion. In a multivariable analysis, the expression 
of PD-L1 was associated with double the cancer-spe-
cific mortality compared with PD-L1-negative cases.  
We hypothesized that this marker could aid in stratify-

FIGURE 2.  
Flowchart of the current structure of the LARCG database

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ing high-risk patients for adjuvant treatment or selecting 
candidates for immunotherapy[19].

Regarding chromatin remodeling genes, our previ-
ous studies revealed that BAP-1 and PBRM-1 were 
strong predictors of unfavorable outcomes in localized 
or locally advanced ccRCC. In a conjugated analysis of 
441 patients with non-metastatic ccRCC, the concom-
itant low expression of BAP-1 and PBRM-1 was associ-
ated with higher mortality rates and double the number 
of recurrences when compared with patients presenting 
both or only one of the markers expressed[20]. Addition-
ally, in 2019, we reported that the low IHC expression of 
BAP-1 and PBRM-1 in 124 metastatic samples was an 
unfavorable feature for patients who underwent metas-
tasectomy. In this study, the low expression of BAP-1 was 
independently associated with 60% higher mortality and 
93% more recurrences. On the other hand, the isolated 
PRBM-1 immunostaining status did not influence the 
outcomes in the multivariate analysis[21].

In a retrospective review of 662 patients with primary 
or metastatic ccRCC, the low expression of SETD-2, 
another chromatin remodeling gene, was associated 
with higher cancer mortality and recurrence[22]. Finally, 
the negative expression of ezrin, an epithelial-mesenchy-
mal transition marker, was associated with poor survival 
rates in a series of 567 patients with localized or locally 
advanced ccRCC[23].

Intending to conclude the LARCG 001 project, we 
will analyze the IHC expression of PTEN, and we need 
to validate the nitric oxide synthase 3 (NOS-3) expres-
sion. In a limited series of 110 patients with diverse RCC 
histologies, high expression of NOS-3 was associated 
with unfavorable pathological features worse, OS in 
univariate analysis (58.1% versus 79.4%; P = 0.033)[24].

Translational research: international 
collaboration groups
Regarding translational research, we developed a 
patient-derived xenograft (PDX) project performed in 
immunodeficient mice at ACCCC in collaboration 
with UCD. We were able to reproduce the anatomo-
pathological and genetic features of the original tumors 
in 27% of the cases. A more intense gene expression 
was evidenced, probably due to the intratumoral 
heterogeneity or the immunodeficiency in the animal 
models. The most impressive was the resemblance 
of venous thrombus in 5 consecutive generations 
originated from one animal[25]. These PDX models can 
be an opportunity for testing future drugs or planning 
adjuvant treatment in patients with advanced disease. 
Once this technique is standardized, we can deliver it in 
other LARCG centers in the future.

Recently, ACCCC (São Paulo), Hospital Pasteur 
(Montevideo), and Hospital Italiano (Buenos Aires) 
sent more than 1500 DNA aliquots from RCC patients, 
and 700 DNA aliquots from healthy control samples, in 
collaboration with the continuation of the Genome Wide 
Association Study project from the American National 
Cancer Institute (NCI), part of the National institutes 
of Health. This international multicenter collaborative 
research encompasses the most recognized institutions 
in the RCC scenario around the world[26]. In this study, 
there were dedicated funds to each LARCG participating 
institutions provided by the NCI to this project.

In support of continuing medical education and best 
practices, there was cooperation between LARCG and the 
Latin American Cooperative Oncology Group (LACOG), 
promoting expert meetings in 2019 that resulted in 2 
manuscripts with recommendations for the best surgical 
and systemic management[27,28]. An update meeting was 
held in the second half of 2022.

Multicentric prospective studies
LARCG has developed a multicenter prospective study, 
led by Hospital Italiano from Buenos Aires. They are 
investigating the 10-year outcomes of patients in active 
surveillance with small renal masses, including those who 
refused surgical or percutaneous treatments. This trial was 
initiated in 2018, and currently has more than 140 enrolled 
patients[3].

Teaching
One of the LARCG scopes is to offer the opportunity for 
international observerships in worldwide recognized 
institutions to young colleagues (urologists or medical 
oncologists). Since 2017, there has been an agreement 
(Residents & Young Doctors Rotation Program) between 
the LARCG and the Department of Medical Oncology and 
Therapeutics Research from City of Hope Comprehensive 
Cancer Center, in Duarte, headed by Professor Sumanta 
Kumar Pal[29]. Yearly, 4 young colleagues (2 urologists and 
2 medical oncologists) from ACCCC and other LARCG 
centers are selected for a 2-month rotation program at the 
City of Hope. The COVID-19 pandemic interrupted the 
program in 2020.

According to this agreement, the travel expenses are 
supported by the Californian Cancer Center. During this 
period, the observers can participate in clinic activities, 
become familiar with the routine of clinical trials, participate 
on tumor boards, participate in inpatient visits, and 
collaborate on the preparation of scientific manuscripts. This 
is a unique opportunity to get world class knowledge in RCC 
and in the clinical management of urological malignancies. 
Six Brazilian and 2 Argentinian young professionals have 
benefited from this program. We hope to promote similar 
educational initiatives for our members in the future.

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Advocacy
In Latin American, oncology patients are not commonly 
well-informed about treatments and their implications. 
However, in the face of regional socioeconomic 
limitations and disparities, some educational and 
advocacy initiatives are necessary.

As a result, the International Kidney Cancer Coali-
tion (IKCC) contacted the LARCG to foster advocacy 
with kidney cancer patients in Latin America between 
2017 and 2018[30]. Immediately, we organized several 
meetings in Mexico, involving patients, associations, 
medical experts, the press, and lawyers. They debated 
aspects of the inequities in health assistance and the 
limited access to some medications or procedures. There 
was an exchange of information among 48 RCC patients’ 
organizations from all continents.

LARCG has contributed to the dissemination of 
information to lay people about kidney cancer risk 
factors, symptoms, and treatments. The group’s other 
task is to demystify clinical trials in this population, 
clarifying for them that participation in a clinical trial 
may be an opportunity to collaborate with scientific 
development and to receive the best available therapeu-
tic options. Meetings have also occurred in São Paulo 
and Lisbon, and a recent report was published regarding 
these meetings[31].

Additionally, we published a study revealing that 
uninsured patients with metastatic disease in Brazil 
receive fewer second- or third-line therapies, or even 
receive less effective therapies in comparison with 

insured or private patients. This was based on a survey 
using a commercial database with more than 4000 
patients[32]. In other evaluation with 273 patients with 
metastatic disease at a tertiary center, we demonstrated 
that uninsured patients have more advanced disease, 
worse performance status, and are less likely than 
insured patients to undergo nephrectomy or systemic 
therapies[33].

Since 2017, IKCC has promoted the annual World 
K id ney Ca ncer Day (W KCD), w it h awa reness 
campaigns, surveys, educational brochures, and websites 
in 14 languages. Each year, the WKCD promotes provoc-
ative debates for questions associated with the daily 
life of the patients, many of which are underreported. 
LARCG has actively participated in the WKCD, and 
launched the 2019 campaign in Latin America. Again 
in June, the IKCC and LARCG joined together again for 
the 2022 WKCD, whose theme was “We must discuss 
therapeutic options”[34].

Conclusion
LARCG was intended to enhance knowledge of and 

promote information about RCC. In few years, we have 
furthered the support, research, teaching, and advo-
cacy for professionals and patients involved with this  
malignancy. Expanding our network and establishing 
further collaborations will result in our partners main-
taining higher levels of education and technical profi-
ciency, and will benefit Latin American patients affected 
by kidney malignancies. Clinical trial development is in 
our future sights.

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33SIUJ.ORG SIUJ  •  Volume 4, Number 1  •  January 2023

The LARCG Latin American Renal Cancer Group: Achievements in Support, Teaching, Research, Collaboration, and Advocacy

https://ikcc.org
https://www.worldkidneycancerday.org
https://www.worldkidneycancerday.org
http://SIUJ.org

