Abstract

Background

There is a lack of epidemiological surveys on soft tissue sarcoma (STS) worldwide. This study aims to assess the global disease burden of soft tissue sarcoma in 204 countries and regions.

Methods

We analyzed the incidence, mortality, and disability-adjusted life years (DALYs) of STS based on the data provided by the Global Burden of Disease (GBD) 2021 study, and assessed the trends in disease burden across different regions, sexes, and age groups. At the same time, we used the Bayesian Age-Period-Cohort (BAPC) model to predict the development trend of the global disease burden of STS.

Results

Globally, over the past 30 years, the number of STS cases has increased from 54,630.92 in 1990 to 96,200.96 in 2021, while the age-standardized incidence rate has decreased by 0.05 per 100,000 people during this period. The age-standardized incidence rate and DALYs rate have respectively declined by 0.14 per 100,000 people and 6.86 years per 100,000 people. In 21 GBD regions, there is a significant positive correlation between Socio-Demographic Index(SDI) and incidence rate (R鈥�=鈥�0.4730, P鈥�<鈥�0.0001). It is projected that the number of STS cases will peak in 2033, reaching 95,591.93 people.

Conclusion

The disease burden of STS has been decreasing, especially regarding mortality and DALYs rates. It鈥檚 more prevalent in developed regions, males, and older. Focused medical prevention and health measures for these groups can help reduce the global disease burden.

Introduction

Soft tissue sarcomas(STS) are a heterogeneous group of cancers that primarily originate from fat, muscle, and other connective tissues [1], with over 50 different histological types [2]. They account for approximately 7-8% of all cancers in children under the age of 20, but represent less than 1% of all adult solid tumors [3,4,5]. It is precisely because of the tissue diversity and low incidence of STS that progress in large-scale research is hindered, and the emergence of new treatment plans is slowed [6]. The main treatment methods currently used for it are surgery, chemotherapy, and radiotherapy. However, even with the best treatment plans, 25鈥�40% of people will eventually experience metastasis [7, 8]. For these patients, chemotherapy has become their only therapeutic option. However, classical studies indicate that even with chemotherapy, their median survival is only one year [9]. In recent years, many new treatment methods have emerged, such as molecular targeted therapy, adoptive T-cell therapy, and immune checkpoint inhibition, and their emergence holds hope for improving the prognosis of STS patients [5, 10]. Given the disease鈥檚 highly lethal and disabling nature, and its prevalence among adolescents, it poses a major global health challenge. Particularly for adolescents undergoing extensive resection of tumor lesions and adjacent normal tissues, it often results in psychological and physical dysfunction, along with social issues such as education, employment, and marriage [11].

Currently, epidemiological surveys for STS are based on clinical registries and regional studies. However, there is a severe lack of information regarding its global disease burden (mortality, incidence, and disability) and the past and future trends of the disease burden. Owing to the uneven distribution of medical resources, the diversity of STS pathology, and the rarity of its incidence, understanding the disease profile of STS in various countries and regions globally aids health administrative departments in the rational allocation of medical resources and the development of effective prevention and control strategies. Additionally, it facilitates researchers in conducting large-scale clinical studies, which can lead to the emergence of new treatment methods. The 2021 GBD study, for the first time, provides us with the opportunity to understand the full picture of the global incidence, mortality, and disability rates of STS. We will use the information it offers to explore the profiles of mortality, incidence, and disability-adjusted life years (DALYs) of STS across different geographical locations, levels of socioeconomic development, genders, and age groups.

Methods

Data sources and population

The GBD 2021 collected, quantified, and estimated 459 health outcomes and risk factors across 204 countries and regions, including indicators such as disease incidence, mortality, and disability, which together form a overall assessment of the burden of disease. The data collection, processing, and methodologies of the GBD can be accessed through previously published research studies [12, 13]. For the GBD data itself, it is available to the public free of charge on their official website, allowing anyone to access the comprehensive health data and analysis provided by the initiative().

Disease definition and burden indicators

The soft tissue sarcomas defined in this study specifically refer to the C49 diseases coded in the ICD-10 version, which include sarcomas of soft tissues and other tissues outside the bone. The disease burden indicators used in this study include: incidence, mortality, and DALYs. SDI is used to evaluate the economic development level of different countries and regions. The SDI is a composite indicator that is calculated based on the distribution lag of income per capita, mean years of schooling for individuals aged鈥夆墺鈥�15, and the total fertility rate among those under the age of 25 [14]. Higher value of SDI means better economic development of the region, SDI in this study is categorised into 5 levels which are: low, middle, high, low-middle, high-middle.

Statistical analysis

We estimate the mortality, incidence, and DALYs rates of STS per 100,000 people, as well as the 95% uncertainty intervals (UI), as indicators to evaluate the disease burden. Estimates of the disease burden leveraged extensive and representative data sources, including literature reviews, cohort studies, population surveys, and administrative data. DALYs were calculated by summing years lived with disability (prevalence 脳 disability weights for sequelae) and years of life lost (deaths 脳 standard life expectancy at age of death). Missing data was handled by advanced methods like MR-BRT and DisMod-MR 2.1. These methods use correction factors and Bayesian approaches to ensure the accuracy and consistency of disease burden estimates [14]. To compare the disease burden between different regions, we age-standardize the disease burden indicators (age-standardized incidence rates (ASIR), age-standardized death rates (ASDR), and age-standardized disability-adjusted life years rate(ASDsR)), which removes the impact of population age profile on the indicators, thereby ensuring the comparability of the research indicators. The estimates of age-standardized rates (ASRs) were calculated using the direct standardization method and weighted by the GBD 2021 world standard population [15]. To analyze age鈥檚 impact on disease burden, we compared crude rates for specific age groups (<鈥�5, 5鈥�9, 10鈥�14,鈥�, 80+) provided by GBD, as GBD 2021 only offers crude rates for these groups. Spearman鈥檚 correlation analysis was used to calculate the coefficient of correlation (r) and p-value among the incidence rate and the SDI. Global maps and regional comparative analyses are used to compare the global distribution and regional disparities of STS disease burden. Additionally, we conducted stratified analyses by gender and age groups to explore the distribution of STS among different demographic populations. We employed the Bayesian Age-Period-Cohort (BAPC) model to forecast the incidence, mortality, and DALYs rates of STS by 2050. This model takes into account the effects of age, period, and cohort, providing a comprehensive approach to understanding the future trends of disease burden. We made use of the R software package, specifically version 4.2.3, along with JD_GBDR (version 2.22 from Jingding Medical Technology Co., Ltd.) for the creation of charts.

Results

Incident burden of STS

Globally (Table听1), the number of STS cases increased from 54,630.92 (95% UI: 46,757.16-63,999.62) in 1990 to 96,200.96 (95% UI: 83,423.51鈥�116,184.87) in 2021. However, the ASIR decreased from 1.21 every 100,000 people in 1990 to 1.16 in every 100,000 people. Compared to 1990, the incidence rate in 2021 increased by 19.02% (95% UI: 10.48鈥�31.35). In 2021, regions with high SDI had the highest number of cases and ASIR among the five SDI regions, with 34,515.04 cases (95% UI: 31,572.99-36,741.83) and an ASIR of 2.05 (95% UI: 1.90鈥�2.16). Low SDI areas show the greatest decline in incidence rate from 1990 to 2021, with a drop of -32.17% (95% UI: -44.40 to -13.59), whereas the largest increase was seen in high SDI regions, amounting to 47.35% (95% UI: 39.97鈥�53.66).

Table 1 Incidence of soft tissue sarcomas between 1990 and 2021 at the global and regional level

Looking at different regions (Table听1), the highest number of cases in 2021 is found in Western Europe, amounting to 17,397.76 (95% UI: 15,678.88-18,763.90), while High-income North America had the highest ASIR, reaching 2.63 (95% UI: 2.48鈥�2.77). From 1990 to 2021, the region with the greatest decrease in incidence rate was Eastern Sub-Saharan Africa, reaching 鈭掆��31.88% (95% UI: -46.16 to -10.08), while the largest growth in incidence rate was in Central Europe, reaching 106.81% (95% UI: 85.41-129.99). From Table. S1 and Fig.听1A, we can see that the region with the lowest ASIR of STS is in the Northern Mariana Islands (0.02, 95% UI: 0.01鈥�0.04), and the region with the highest ASIR is in Germany (2.77, 95% UI: 2.45鈥�3.05).

Fig. 1

The 2021 global disease burden of STS in 204 countries and territories. (A) age-standardized incidence rate; (B) age-standardized deaths rate; (C) age-standardized DALYs rate

Among the 21 different GBD regions (Fig.听2), the significant positive correlation between SDI and ASIR was found (R鈥�=鈥�0.4730, p鈥�<鈥�0.0001), and this positive correlation also exists between different countries (Figure. S1). This observation indicates that the incidence of STS is greater in areas with a more advanced level of economic development. From the ASIR time trend chart from 1990 to 2021 (Fig.听3), we can see that the incidence rate in high SDI areas has consistently been at the top for nearly 30 years. However, the region with the maximum decline in ASIR over the past 30 years is in low SDI, with the number of cases every 100,000 people decreasing by 0.33.

Fig. 2

The association between SDI and age standardized incidence rate from 1990 to 2021 in 21regions

Fig. 3

Trends in age-standardized incidence rate of STS from 1990 to 2021 in global and 5 SDI regions

Deaths and dalys burden of STS

In 2021, the estimated number of global deaths due to STS was 50,203.14 (95% UI: 43,232.00鈥�61,280.38), with ASDR of 0.60 (0.52鈥�0.74), representing a decrease of 0.14 deaths per 100,000 people compared to 1990( Table. S2). The global number of DALYs lost attributed to STS is assessed at 1,677,891.91 (95% UI: 1,428,208.70-2,115,701.39), with an ASDsR of 20.54 (17.46鈥�26.09), representing a decrease of 6.86 DALYs per 100,000 people compared to 1990 (Table. S3). In the five SDI regions, the low SDI region had the greatest ASDR and ASDsR in 2021, reaching 0.95 per 100,000 people and 33.41 years, respectively. Conversely, between 1990 and 2020, the high SDI regions experienced the largest increases in mortality rates and disability-adjusted life years (DALYs), with increases of 36.15% (95% UI: 29.78鈥�40.81) and 11.66% (95% UI: 7.16鈥�15.07), respectively (Table. S2-3). From the time trend charts of ASDR and ASDsR across the five SDI regions from 1990 to 2021, we can observe that, with the exception of the high SDI region, both ASDR and ASDsR have shown a declining trend, and this trend is most pronounced in the low SDI region (Figure. S2-3). The 2021 ASDR world map indicates that Uganda has the highest mortality rate, reaching 1.96 (95% UI: 1.30鈥�3.28), followed by Somalia, with a rate of 1.92 (95% UI: 1.23鈥�3.17) (Table S2 and Fig.听1B). The 2021 ASDsR world map shows that South Sudan has the highest DALY rate, reaching 66.46 (95% UI: 40.26-112.09), followed by Uganda with a rate of 66.01 (95% UI: 43.55-109.78) (Table S3 and Fig.听1C).

Global disease burden stratified by sex and age

From Fig.听4, we can see that from 1990 to 2021, the global incidence rate for males has remained relatively stable, while that for females has slightly decreased, but the incidence rate for males is significantly higher than that for females. However, both the ASDR and ASDsR show a clear downward trend for males and females, with males consistently having higher rates than females (Figure. S4-5). In 2021, within different age groups, the number of incident cases, deaths, and DALYs for males is generally higher than for females. Moreover, with increasing age, the incidence rate, mortality rate, and DALY rate all show an upward trend (Fig.听5). Globally, compared to 1990, the incidence rate in the population aged 70 and above has increased significantly in 2021, with the greatest increase in the 80鈥�+鈥塧ge group. In contrast, there is a downward trend in the group under 5 years of age. In low SDI regions, the incidence rate has decreased in all age groups except for the 80鈥�+鈥塧ge group, where it has increased. In the other four SDI regions, the incidence rate has also increased in people aged 70 and above, while it has decreased in children under 5 years of age (Fig.听6). Globally and across the five SDI regions, there has been a consistent decline in mortality and DALY rates among various age groups from 1990 to 2021 (Figure. S6-7).

Fig. 4

Trends in age-standardized incidence rate of STS in male and female from 1990 to 2021 in global

Fig. 5

The burden of disease indicators for STS across different age groups in 2021: (A) incidence number and rate; (B) deaths number and rate; (C) DALYs number and rate

Fig. 6

Comparison of incident rate of STS across different age groups in global and five SDI regions (1990 and 2021)

Projections for the future global burden of STS

From Table. S4 and Figure. S8, it can be observed that the incidence of STS will reach its peak by 2033, at 95,591.93 (95% UI: 87,472.31鈥�103,711.55), after which a gradual decline is expected, with the forecasted incidence for 2050 being 90,464.91 (95% UI: 76,270.23鈥�104,659.60). The mortality rate and DALY rate are both expected to decrease annually, with projections estimating a death rate of 0.44 per 100,000 people (95% UI: 0.37鈥�0.50) and a DALY rate of 13.07 (95% UI: 11.14-15.00) by 2050 (Figure. S9-10).

Discussion

This study provides a comprehensive epidemiological analysis of the global burden of STS, including trends in incidence, mortality, and DALYs across various regions, socioeconomic statuses, genders, and age groups from 1990 to 2021. Globally, the incidence rate of STS has remained relatively stable, while both the mortality rate and DALYs rate have declined. Looking at different levels of economic development, the highest morbidity rates are found in areas with high SDI, while mortality and DALYs rates are highest in areas with low SDI. The rates of incidence, mortality and DALYs for man are all higher than those for females, and these rates tend to increase with age.

Previous epidemiological studies on STS were based on national and regional registries. According to the analysis provided by the U.S. Surveillance, Epidemiology, and End Results (SEER) database, between 1973 and 2006, the incidence of STS was 5.9 cases in every 100,000 persons [3]. In the 27 European Union countries, the overall estimated incidence rate is 5.6 cases per 100,000 people [16]. However, Data from the Austrian National Cancer Registry shows an Austrian national STS incidence of only 2.4 per 100,000 [17], while the Japanese Orthopaedic Association鈥檚 registry data indicates that Japan鈥檚 2019 STS incidence was even lower, at 2 per 100,000 [18]. However, the disparities in the research conclusion are not only due to the actual incidence, but also to the differences in case types during data collection. For instance, the high incidence rate in the US SEER database is due to the inclusion of Kaposi鈥檚 sarcoma. In contrast, Japan鈥檚 lower incidence rate might be because sarcomas in the peritoneum, retroperitoneum, and uterus are underestimated. In our study, the 2021 global incidence rate is 1.16 per 100,000 people. In areas with varying economic development, the highest incidence rate of 2.05 per 100,000 was reported in high SDI areas. In regions with high economic development, the high incidence of STS in regions with high economic development may be due to a variety of factors, such as environmental pollution, population ageing and a well-developed health-care system [19, 20]. The incidence of cancer, often defined as a disease about aging, rises dramatically with age [21, 22], and average life expectancy in economically developed countries is often higher than in less developed areas. Another possible reason is that in regions with high economic development, advanced medical facilities increase the likelihood of early diagnosis [23]. Incidence rates are higher in men than in women, potentially related to the higher attributable burden of cancer in men, such as smoking, drinking, occupational exposure [24, 25].

During the last 30 years, global STS death rate falls by 0.14 per 100,000 people, and the DALYs rate has dropped by 6.86 years per 100,000. These declines are seen across all SDI regions, with the most significant reductions in low SDI areas, where mortality fell by 0.38 per 100,000 and DALYs by 19.31 years per 100,000. The data indicates that significant progress has been made in treating STS, leading to substantial improvements in mortality and disability rates. In the past, the main treatment for STS was surgery, supplemented by preoperative or postoperative radiochemotherapy. In recent years, with the emergence of new medical technologies, such as new chemotherapy regimens [26, 27], antibody-drug conjugates that target and kill cancer cells [6], and an immunotherapy that triggers the body鈥檚 immune response to assault cancer cells [28, 29], the prognosis for patients has been greatly improved. The more noticeable improvement in the prognosis of STS patients in underdeveloped countries should be related to a combination of factors such as the improvement of healthcare systems, the increase in health expenditure, the gradual coverage of medical insurance, and international cooperation [30,31,32].

In the future, when formulating public health policies for STS, it is necessary to increase the coverage of medical equipment and personnel in economically underdeveloped areas, enhance the accessibility and inclusiveness of medical resources, and enable early diagnosis and treatment of diseases. It is also crucial to improve public recognition of the importance of STS prevention and treatment, and to change unhealthy lifestyle habits such as prolonged sitting, smoking, and drinking. Coordinate global case resources to conduct large-scale clinical studies on different pathological types of STS, promoting advancements in treatment plans. At the same time, further research and exploration into the mechanisms of disease development is needed to develop new therapeutic approaches.

Strengths and limitations

Currently, global burden of disease studies on STS are lacking. Our study, based on the 2021 GBD database, presents a well-rounded assessment of the global disease burden of STS (incidence, mortality, DALYs). It provides data support for subsequent disease prevention and containment as well as for the development of public health policies. For example, our study indicates that the SDI is positively correlated with the incidence of STS, with a higher incidence observed in the elderly population. We can implement cost-effective diagnostic and therapeutic measures in high-SDI regions with an aging population to improve early diagnosis and effective treatment of the disease. We estimate that the disease burden of STS will peak around 2033, which highlights the urgency of collecting data on different histological subtypes of STS and accelerating clinical trials for rare subtypes. This study also has some limitations. First, in remote and underdeveloped areas, the scarcity of medical resources, insufficient diagnostic capabilities, and incomplete case registration systems often lead to underdiagnosis, delayed diagnosis, or even concealed diagnosis of STS. Under these circumstances, the disease burden in these regions is often underestimated, and the actual incidence and mortality rates may be higher. Second, the 2021 GBD did not collect data on risk factors related to STS, making it impossible to conduct an attributable analysis of the disease. The lack of clarity regarding risk factors leads to an inability to implement targeted preventive measures for high-risk populations, allocate medical resources effectively in high-risk areas, and formulate public health policies based on scientific evidence. Third, there are errors in the collection and modeling processes of the GBD data. For example, limitations in data sources, inaccuracies in model estimations, and the lagging nature of data. However, the GBD has implemented several measures to mitigate the impact of this limitation on the conclusions, such as excluding low-quality data, cross-validating with external data, and using 95% uncertainty intervals.

Conclusions

Our research indicates that in the last 30 years, there has been a downward trend in the global disease burden of STS, especially regarding mortality and DALYs rates. The high incidence rate in high SDI areas and the high fatality and disability rates in low SDI areas require us to implement targeted measures to control STS. It is necessary to enhance diagnostic and treatment capabilities in underdeveloped regions, adopt targeted prevention and treatment strategies, and modify avoidable risk factors. Furthermore, coordinating global case resources and conducting clinical research on different histological types of STS is essential for advancing our understanding and treatment of the disease.