Cancer is currently one of the main social, economic, and public‐health challenges (1). Globally, prostate cancer (PCa) was the second most prevalent cancer among men and ranked as the fifth leading cause of cancer‐related mortality in 2022 (1). PCa incidence varies widely between regions, with the highest rates reported in North America and Oceania, and the lowest in Africa and Asia (1). Regarding mortality, this pattern shifts markedly. In regions of Africa and parts of the Caribbean, mortality rates are high despite low incidence, in contrast to highly developed areas such as Northern Europe and North America, where, despite high incidence, mortality remains low (1).

Latin America and the Caribbean (LAC) is a region comprising 49 countries and territories (the term “territories” groups overseas and unincorporated areas) and can be subdivided into three subregions based on geographic location: Central America (8 countries), South America (12 countries and 1 territory), and the Caribbean (13 countries and 15 territories). In LAC the estimated PCa incidence and mortality rates are 58.0 and 13.9 per 100,000 men, respectively, compared with 73.5 and 8.3 in Northern America, 71.9 and 11.5 in Oceania, and 59.9 and 11.2 in Europe (2). This contrast with Asia, where incidence and mortality rates are 12.6 and 3.8, respectively (2). Within LAC, the highest PCa incidence and mortality rates were seen in the Caribbean, followed by South America, and, at the lowest level, Central America (Figure 1A) (2). The trend in PCa mortality between 1990 and 2020, based on Globocan data, for South America and Central America and the only two Caribbean countries with available data (Cuba and Puerto Rico), shows a striking increase in Cuba and a decrease in Puerto Rico, both Caribbean islands but with distinct geopolitical statuses, since Puerto Rico is an unincorporated territory of the United States, whereas Cuba is an independent state (Figure 1B) (2).

PCa incidence and mortality rates (1), and reported ethnic composition for each LAC country or overseas territory, are presented in descending order of mortality (3–26) (Figure 1C), where a potential association between higher mortality rates and a greater proportion of African ethnic ancestry is observed. Countries with the highest mortality were primarily Caribbean islands, except for Guadeloupe (a French overseas territory), which does not rank among them despite the fact that 85% of its population is of African descent. Interestingly, Martinique (also a French overseas territory) did not show particularly high mortality, although ethnicity data are not available for this territory. Furthermore, countries with the highest proportion of Native American ancestry, mostly located in Central America, tend to have a lower proportion of African ancestry and lower PCa mortality rates (Figure 1C).

The influence of ancestry on tumor biology and behavior suggests underlying differences in tumor profiles, especially in PCa. Multiple studies have reported a higher burden of PCa in men of African ancestry, linked to their West and West-Central African heritage from the transatlantic slave trade, which has been associated with earlier onset and more aggressive tumor behavior compared with men of other ancestries (27, 28). This burden is even greater in Black Caribbean populations and is also evident in the United Kingdom, where most Black men are of Afro-Caribbean or West African descent (29). These patterns likely reflect complex interactions between population-specific genetic ancestry and mixed heritage across regions, together with environmental factors, like the socioeconomic environment, that have been shown to modulate how genetic ancestry influences prostate cancer risk (28, 30). These complex interactions highlight the need for targeted strategies that extend beyond self-reported race and incorporate biomarkers, like West African ancestry–associated SNPs, which have been associated with improved prediction of biopsy positivity and clinically significant disease in African American men, highlighting the role of biomarkers in refining risk stratification and improving early detection in high-risk populations (31).

Traditionally, the term biomarker is defined as a characteristic that can be measured precisely and reproducibly, and that indicate normal or pathological biological processes, or responses to exposures or interventions (32, 33). However, due to the complexity of tumor biology, not all of these characteristics have undergone a formal validation process, and some remain at an exploratory stage. Therefore, in this review, the term potential biomarkers will be used to encompass all these findings, ranging from well-established biomarkers like PSA or PCA3 to emerging ones that are currently being studied, not only as susceptibility biomarkers but also in other areas like prognosis or treatment selection (34, 35).

LAC is characterized by high PCa mortality rates in certain areas and marked ancestral heterogeneity, with populations exhibiting varying proportions of Afro-Caribbean, Native American, and European ancestry shaped by historical processes such as colonization and the transatlantic slave trade. In this context and given the relevance of the molecular landscape for the management of this disease, this article aims to conduct a scoping review of studies on potential biomarkers related to PCa carried out in LAC countries/territories. This review will highlight the interests and advances in this field within the region, while also identifying the needs and knowledge gaps that must be addressed.

This scoping review was conducted based on the PRISMA-Scr (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines (36).

A total of 1979 articles were identified. After excluding duplicates and screening titles and abstracts, 270 articles underwent full-text review, and 138 of these met the inclusion criteria and were finally included. The detailed search and selection process is visually represented in the PRISMA flow diagram (Figure 2).

These articles were conducted in 17 LAC countries/territories: 7 from the Caribbean, 7 from South America, and 3 from Central America. The number of articles and potential biomarkers studied, classified by category and country, are presented in Table 1. The articles were categorized as follows: related to the risk of developing PCa (n=74); screening, early detection, and diagnosis (n=13); prognosis (n=48); treatment (n=10); and others (n=12). A total of 19 articles were classified into more than one category. Similarly, 342 potential biomarkers were reported and classified as follows: 146 related to the risk of developing PCa; 20 to screening, early detection, and diagnosis; 147 associated with prognosis; 14 linked to treatment; and 59 to the “others” group. A total of 44 biomarkers were classified into more than one category.

The results are described below, grouped according to their category.

The populations of LAC have a genetic admixture of Indigenous, European, and African ancestry which, along with other factors, may influence the behavior of PCa. In this context, the aim of this study was to identify the available regional evidence in published studies on potential biomarkers associated with PCa. Across different focus categories and countries/territories, the most studied biomarkers were those related to AR, the genes GSTM1, GSTT1 and GSTP1, and vitamin D metabolism.

Regarding AR, 5 studies from Brazil, Mexico, and Ecuador evaluated the association between CAG repeat length in the AR gene and the risk of PCa, three of which reported an increased risk with ≤21 CAGs (49, 66) y <19 CAGs (67). This partially aligns with the meta-analysis by Qin et al. (177), which included 51 studies from America, Africa, Asia, and Europe, and found an association between ≤20 CAGs and a higher risk of PCa. However, the other two studies did not find significant associations (99, 109). Likewise, the relationship of this biomarker with prognosis and diagnosis was also investigated; in Martinique, an association between >20 CAGs and lower PCa aggressiveness was reported (74), and in Mexico, its ability to differentiate PCa from BPH was observed (112). Similarly, other related potential biomarkers, such as AR protein expression levels in prostate tissue, and AR variant 7, were evaluated as diagnostic biomarkers and predictors of treatment response, respectively (111, 161).

With respect to glutathione S-transferases, they catalyze the conjugation of reduced glutathione to diverse compounds, enabling the detoxification of xenobiotic-derived substances, yet they can also activate oxidative metabolites with carcinogenic potential. In this review, several studies evaluated the GSTM1 gene, and although most did not yield significant results, a study from Chile by Acevedo et al. (46) found that the Null genotype was associated with increased susceptibility to PCa. In Guadeloupe, two studies associated a higher risk with the presence of at least one functional allele of GSTT1 (47) and with having more than two copies of this same gene (48). The meta-analysis by Gong et al. al (178)., which included studies involving Caucasian, African, and Asian individuals, found that the Null genotypes of GSTM1 and GSTT1 were associated with a higher risk of PCa. While Malik et al. (179) reported that the genotype Null of GSTM1 was associated with increased risk in Asian and European populations, and genotype Null of GSTT1 only in African populations. This may indicate differential behavior of these genes in PCa susceptibility, linked to the continental ancestry of each population.

The relationship between glutathione S-transferase genes and PCa prognosis was also studied, with the study by Acevedo et al. (135) in Chile standing out, which reported higher overall mortality in patients with the Null genotype of GSTM1, an association not previously described in other studies. Similarly, the study by Cotignola et al. (136) in Argentina found an association between a polymorphism of GSTP1 and a lower biochemical recurrence-free survival. Although no significant association was found with polymorphisms of GSTT1 and GSTM1, lower biochemical recurrence-free survival and higher recurrence were observed in patients when combining the genotypes of all three GST genes in multivariable models. This contrasts with the study by Nock et al. (180) in the United States, which found no differences in biochemical recurrence related to GSTP1 gene polymorphisms in African American subjects, but did report a significant association with the Null genotype of GSTT1. These findings could also suggest differences in PCa prognosis based on the ancestry of the respective populations.

As for vitamin D metabolism, several potential biomarkers related to the VDR, such as the rs2238135 (57) polymorphism and the presence of more than 20 adenine repeats in the 3’ untranslated region of the gene, were associated with a higher risk of PCa (74); the latter was also linked to greater aggressiveness (74). These findings are consistent with studies conducted in populations from the United States (181, 182). Likewise, high serum levels of 25-hydroxyvitamin D were associated with a higher risk of PCa in Jamaica (76), which aligns with the meta-analysis by Xu et al. (183), showing a similar association in studies from Europe and the United States. This could be explained by the fact that levels of calcidiol, an intermediate metabolite generated in the liver from calcifediol, have been correlated with high levels of insulin-like growth factor 1 (184), which activates the mitogen-activated protein kinase and phosphoinositide 3-kinase pathways, and promotes cell proliferation in PCa (183, 185).

In relation to the potential biomarkers associated with PCa screening, early detection, and diagnosis, these biomarkers were primarily evaluated in relation to PSA levels ≥ 4.0 ng/mL as early detection biomarkers. This is largely due to their high sensitivity (0.90) but low specificity (0.20), which leads to a substantial number of unnecessary biopsies, as reported in reviews included in clinical practice guidelines. The primary application evaluated for these biomarkers would be to increase the specificity of PSA and thereby reduce unnecessary biopsies (186–188). Detailed information from the included articles regarding each of these biomarkers in relation to PSA is provided in Supplementary Table 3. Among the biomarkers included in this study, PCA3 is the only one currently addressed in clinical practice guidelines at the level of early detection; however, its usefulness in guiding biopsy decisions remains uncertain, and the supporting evidence is considered weak (186). This underscores the importance of conducting further studies to determine whether PCA3 has clinical utility in LAC.

Regarding the articles associated with treatment, there was a lack of randomized clinical trials in the final selection of studies. Although some identified studies included centers in LAC, they were excluded because they did not report results disaggregated for the LAC population (166, 167). This is particularly concerning in light of evidence showing low enrollment of individuals from minority groups in clinical trials and the resulting lack of population-specific data (189). On the other hand, although a hypothetical cost-analysis study suggested a potential cost-saving role for androgen receptor splice variant 7, direct clinical evidence in LAC is still required, as its use is not routinely recommended in clinical practice guidelines, even though some evidence suggests its utility (161, 186). Lastly, it is worth highlighting the development of trials based on innovative therapies developed within the region, which are on par with those conducted in high-income countries, such as dendritic cell-based vaccines used as neoadjuvant treatment, demonstrating the region’s potential to develop therapies tailored to its population (190, 191).

Overall, most of the studies identified were conducted individually in continental countries such as Brazil, Chile, Argentina, México, Ecuador and Colombia, which have a lower proportion of African ancestry compared to island nations like Haiti or The Bahamas (Figure 1). This may be explained by the lower investment in research in these insular countries/territories, with some exceptions such as Puerto Rico (192). This highlights a significant knowledge gap regarding the genetic profiles and specific characteristics of these populations, which could be linked to their higher PCa mortality rates and represent potential areas for the implementation of preventive and/or therapeutic measures. Future efforts should prioritize multicentric and collaborative studies, as well as the establishment and maintenance of shared biobanks that integrate biological, molecular, and clinical data, thereby strengthening PCa research capacity in LAC. However, while strengthening research on biomarkers is essential, these discoveries can only translate into meaningful clinical benefit if accompanied by improvements in healthcare coverage that facilitate timely diagnosis, treatment, and follow-up for the broader population.

Among the limitations of this study, the most notable is the inability to perform a meta-analysis due to the great variability of the studies found. Furthermore, well-established biomarkers may be underrepresented in the literature reviewed because they were not the main focus of current studies in the region; an example of this is the current use of commercial panels in clinical practice in LAC countries, yet no studies evaluating them were identified. Consequently, the findings do not reflect the current utilization of biomarkers and should not be used to compare patterns of use across regions; however, they highlight prevailing research trends in biomarker investigation in the region. In addition to the disparity between the countries of origin of the articles, most commonly from Brazil, Mexico and Chile, it was observed that the studies did not always include a sample representative of the ethnic composition of their country. An example is the study by Nóbrega et al. (128) in Brazil, whose sample had 85.6% European ancestry and 14.4% African ancestry, which contrasts with the values reported by de Souza et al. (3), which reported weighted average ancestry proportions of 68.1%, 19.6%, and 11.6%, for European, African, and Native American populations, respectively. Furthermore, many studies did not include an ancestry analysis of the study population and instead limited themselves to describing ethnic origin. Future studies should ensure the inclusion of representative populations and incorporate ancestry analysis to enhance the validity and regional relevance of their findings.

The majority of studies included in this review evaluated various types of potential biomarkers in relation to PCa risk and prognosis. The most commonly studied biomarkers were those associated with AR, glutathione S-transferase enzymes, and vitamin D metabolism. Compared to studies from other regions, some of these biomarkers showed similar expression patterns, while others differed importantly, likely reflecting genetic differences associated with continental ancestry across populations. Likewise, it was noted that most studies were conducted in continental countries of LAC with a lower proportion of African ancestry, whereas island countries/territories with higher African ancestry and higher PCa mortality rates were underrepresented. Future research in the region should address these geographic gaps and prioritize collaborative studies that provide a more comprehensive understanding of the landscape of PCa in LAC. These developments, in conjunction with appropriate improvements in access to healthcare, could facilitate the development of targeted strategies for prevention, diagnosis, and treatment for the LAC population.