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. 2024 Nov 25:40:100952.
doi: 10.1016/j.lana.2024.100952. eCollection 2024 Dec.

Cholangiocarcinoma in Latin America: a multicentre observational study alerts on ethnic disparities in tumour presentation and outcomes

Leonardo G da Fonseca  1   2 , Laura Izquierdo-Sanchez  3   4 , Pedro H Hashizume  1 , Yanina Carlino  5 , Estefanía Liza Baca  6 , Cristina Zambrano  7 , Santiago A Sepúlveda  8 , Andrea Bolomo  5 , Pedro M Rodrigues  3   4   9 , Ioana Riaño  3   4   10 , Andre Boonstra  11 , Jose D Debes  11   12   13 , Luis Bujanda  3   4 , Flair J Carrilho  1 , Marco Arrese  14 , Juan C Roa  8   15 , Enrique Carrera  16 , Javier Díaz Ferrer  6 , Domingo Balderramo  5 , Claudia P Oliveira  17 , Jesus M Banales  3   4   9   18
Affiliations

Cholangiocarcinoma in Latin America: a multicentre observational study alerts on ethnic disparities in tumour presentation and outcomes

Leonardo G da Fonseca et al. Lancet Reg Health Am. .

Abstract

Background: Cholangiocarcinoma (CCA) represents a global health challenge, with rising incidence and mortality rates. This study aimed to elucidate the clinical course and practices of CCA in Latin America.

Methods: This observational cohort study investigated individuals diagnosed with CCA between 2010 and 2023 at five referral centres across Latin America. Demographic, biochemical, and clinical data were analysed.

Findings: A total of 309 patients were enrolled, demonstrating a balanced distribution of CCA subtypes (intrahepatic, perihilar, and distal), with Hispanics and Caucasians as the predominant ethnic groups, followed by Africans. Major risk factors identified included age, diabetes, obesity, MASLD, bile duct stones, and cholecystitis. Disparities in overweight/obesity prevalence were noted among CCA subtypes and ethnicities, with higher rates in extrahepatic CCA and among Hispanics and Caucasians. At diagnosis, 72% of patients had ECOG-PS scores of 0-1, with disease presentations ranging from localized (47%) to locally advanced (19%) and metastatic (34%). Patients who did not receive any anti-cancer therapy exhibited a median survival of 2.3 months. Survival rates significantly improved across treatment modalities, with surgery yielding the longest (34 months), followed by chemotherapy (8 months). Notably, Africans presented with worse ECOG-PS scores and more advanced disease, while Hispanics were less frequently treated with chemotherapy for advanced disease, contributing to lower survival rates (8.3 and 6 months, respectively) compared to Caucasians (12.6 months).

Interpretation: The high prevalence of late-stage CCA diagnosis in Latin America, particularly among individuals of African ethnicity, coupled with a significant proportion of Hispanic patients not receiving chemotherapy, underscores the dismal prognosis for these patients. These findings reveal structural challenges in cancer screening and healthcare access among diverse ethnic backgrounds and lower socioeconomic statuses in the region. Urgent measures are needed, including the identification of preventable risk factors, raising awareness among high-risk populations, and establishing equitable health coverage to address these disparities.

Funding: European Union's Horizon 2020 R&I Program, Incyte Bioscience International Sàrl, and European Association for the Study of the Liver (EASL).

Keywords: Biliary cancer; Ethnicities; Management; Risk factors; Subtypes.

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Conflict of interest statement

The LATAM-CCA Registry, which is part of the International Cholangiocarcinoma (INT-CCA) Registry, was competitively funded by the European Union’s Horizon 2020 Research and Innovation Program [grant number 825510, ESCALON], Incyte Bioscience International Sàrl (grant awards 2020 and 2023 to JMB), and the European Association for the Study of the Liver (EASL; Registry grant awards 2016, 2019 and 2023 to JMB). Other funding sources: Instituto de Salud Carlos III (ISCIII) [FORT23/00026, FIS PI18/01075, PI21/00922 and Miguel Servet Program CPII19/00008 to JMB; Sara Borrell CD19/00254 and Miguel Servet Program CP22/00073 to PMR] co-funded by the European Union. “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC “Rare Cancer” grant AECC17/302 to JMB, and AECC Postdoctoral grant POSTD246369IZQU to LI-S), Asociación Española para el Estudio del Hígado (AEEH, Juan Rodes Postdoctoral grant to LI-S). PSC Partners US (to JMB) and PSC Supports UK (to JMB). AMMF-The Cholangiocarcinoma Charity (to JMB and PMR). “Diputación Foral Gipuzkoa” (2020-CIEN-000067-01, 2021-CIEN-000029-04-01 and 2023-CIEN-000008-01 to PMR); Department of Health (2022111070 to PMR; 2017111010, 2019222054, 2020333010, 2020111077, 2022333032, 2023333005 to JMB), and Department of Education (POS_2022_1_0041 to LI-S) of the Basque Country. Pontificia Universidad Católica de Chile (PBV2302 to MA) and Chilean Government through Fondo Nacional de Desarrollo Científico y Tecnológico, (Fondecyt Project, 1241450 to MA, and Fondecyt 1221345 to SAS). Millennium Institute on Immunology and Immunotherapy (ICN09_016 and ICN 2021_045 to JCR). The funding sources were not involved in study design, data collection and analysis, decision to publish, or preparation of the article. Moreover, JMB declares research grants (from Incyte, Albireo, and Cymabay), personal fees for lecturer (from Incyte, Astra Zeneca, Intercept, Eisai and Advance), and consulting role (for Albireo, Ipsen, Cymabay, Astra Zeneca, Jazz Pharmaceuticals, Servier, Ikan-Biotech, OWL-Rubió Metabolomics). MA declares personal fees for lecturer (from Siemens and Echosens), and consulting fee (for Inventiva). The remaining authors have no conflicts to report. The funding sources had no involvement in study design, data collection and analysis, decision to publish, or article preparation.

Figures

Fig. 1
Fig. 1
Survival rates of patients with CCA in the LATAM cohort sorted by ethnicity. Kaplan–Meier analyses and Multivariable Cox regression models were conducted to compare the long-term outcomes among patients with CCA across different ethnic groups. Overall survival was measured from the time of CCA diagnosis until death or the last medical visit. Proportional hazard testing was performed in the Cox regression model to evaluate the effect of the ethnic group on survival while controlling for country of origin. Abbreviations: CCA, cholangiocarcinoma; IQR, interquartile range; HR, hazard ratio; CI, confidence interval.
Fig. 2
Fig. 2
Flowchart describing the therapeutic management and outcomes for patients with CCA in the LATAM cohort. The chart categorizes patients according to their initial therapeutic strategy: surgery, chemotherapy, or best supportive care. Further information is provided for patients undergoing tumour resection, including details on resection margins and adjuvant chemotherapy. For chemotherapy recipients, details on the type of chemotherapy administered and radiologically assessed response are included. Median relapse- or progression-free survival was calculated using Kaplan–Meier analysis. Only individuals with at least one-year of follow up were included in the analysis, see Supplementary Fig. S1 for more details. Additionally, three patients were treated with locoregional therapies, which, due to their low number, were excluded from the treatment-related analyses. Abbreviations: Gem, Gemcitabine; GemCis, Gemcitabine plus cisplatin; GemOx, Gemcitabine plus oxaliplatin; RFS, recurrence-free survival; PFS, progression-free survival.
Fig. 3
Fig. 3
Survival rates among patients with CCA in the LATAM cohort based on their initial treatment. Kaplan–Meier analyses and Multivariable Cox regression models were conducted to compare long-term outcomes among patients with CCA following their first therapeutic strategy. Overall survival was measured from the start of initial treatment until death or the last medical visit. Abbreviations: IQR, interquartile range; HR, hazard ratio; CI, confidence interval.
Fig. 4
Fig. 4
Graphical abstract.
See this image and copyright information in PMC

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