Introduction
Gynecological sarcoma (GS) is a type of rare malignancy, accounting for 13% of all sarcomas and 3–4% of all gynecological malignancies. The most common primary site of GSs is the uterus (83%), followed by the ovaries (8%), vulva and vagina (5%) and other gynecologic organs (2%) [
1]. GSs are more aggressive than other gynecological malignancies [
2‐
4]. The common histological types of GSs comprise of carcinosarcoma (malignant mixed mesodermal tumor), leiomyosarcoma, endometrial stromal sarcoma, adenosarcoma and undifferentiated sarcoma [
5‐
10].
Given the low incidence and histological diversity, few studies have focused on GSs. Though a few studies reported the epidemiology of GSs with limited histological subtypes [
8,
9], or among pediatric population [
11,
12], there is no comprehensive study focused on the epidemiology of adult GSs in the US. In addition, the trends of survival and first-course treatments for GSs have not been adequately addressed.
This cross-sectional epidemiological analysis aimed to estimate the incidence, prevalence and incidence-based mortality in adult patients with GSs, and described the trends of survival and initial treatments in the US by using the Surveillance, Epidemiology, and End Results (SEER) 9 registries, which include approximately 10% of the US population.
Discussion
To the best of our knowledge, this is the first US subpopulation-based study, using a large amount of data integrated in the SEER program, to perform a comprehensive analysis of GS cases in the US from 1975 to 2015, with a focus on epidemiology, survival and initial treatment. Some notable findings are discussed below.
In this study, we found that the incidence of GS gradually increased by 1.0% each year, but it increased to 1.3% each year in the last decade. This increase may be partly related to radiation, exogenous estrogen and obesity [
14,
15]. The changes in trends in both age subgroups were similar, while the incidence in the population aged ≥ 55 years was three or more times than that of the population aged 20–54 years from 1975 to 2015. In addition, the incidence of all GSs peaked at a relatively older age period. Notably, the incidence and increasing trend were more pronounced in Black population. This was consistent with the results of a previous study on the epidemiological analysis of uterine sarcomas in the US [
8]. A probable explanation could be that obesity was higher among Black women in the US, which was a risk factor for GS occurrence [
14,
15].
Corpus and uterus GS was the main subtype of all GSs in this study, and it increased significantly during the last three decades (an APC of 1.5 for 1986–2015). In addition, the 20-year limited-duration prevalence and the annual prevalence of corpus and uterus GS also increased. The probable reason could be that the most common histological subtype of GS was carcinosarcoma, accounting for approximately 50% [
5], which had genetic predisposition in the corpus and uterus [
16]. For the past four decades, ovary GS had the highest increasing trend, followed by other sites GS.
GSs with different SEER stages presented with different trends of incidence. GSs with regional and distant stages increased significantly, while GSs with unknown stage decreased significantly. The evolution and improvement of diagnostic techniques, such as computed tomography (CT), magnetic resonance imaging, positron emission tomography-CT, could help to better characterize the stage at diagnosis [
17,
18]. Notably, the increase in incidence of local GSs was not obvious.
Previous studies demonstrated that the survival of ovary GS was inferior to uterine GS [
19,
20]. In this study, we also found better 3-year and 5-year CSS rates in corpus and uterus GS compared to ovary GS. A significantly higher proportion of distant stage of ovary GS at diagnosis (73.3%) and the low 3-year (22.2%) and 5-year (14.4%) CSS rates for ovary GS at distant stage contributed to the worst survival. Most patients with corpus and uterus GS or other sites GS had abnormal vaginal bleeding, which facilitated early diagnosis and timely treatment. In contrast, patients with ovary GSs presented with non-specific symptoms, which led to delay in diagnosis [
10,
21]. Besides, the higher proportions of local and regional stages in cervix uteri GS cases, as well as relatively better survival for cervix uteri GS cases with local and regional stages, contributed to the best 3-year and 5-year CSS rates for overall cervix uteri GS cases.
In this study, the main treatment modality for GS was surgery, which was consistent with previous reports [
10,
22]. In addition, individualized, diversified and synthesized treatments based on the heterogeneity of each GS case are warranted [
7,
23‐
25]. Moreover, targeted therapy and immunotherapy were considered as novel and promising treatment modalities for GSs [
1,
26‐
28]. There is no standard treatment regime for some rare GSs, such as ovary GS [
10,
21]. Some studies suggested the treatment strategy of ovary GS should be consistent with that of epithelial ovarian cancer [
4], while other studies recommended that the treatment for ovary GSs should follow the principle of treatment for corpus and uterus GS [
29]. Further studies are warranted to better explore the standard treatment for rare GSs.
This study firstly summarized the trends of treatment patterns of GSs over the years in the US. We found that the proportions of surgery and single treatment decreased over the years. This might be due to the increasing incidences of GSs with regional and distant stages. Instead, the proportion of multiple treatments increased significantly. The increased availability of chemotherapy and radiation treatment data might be related to improved access and reporting mechanisms for treatment information provided outside the hospital setting. These may explain the improvements of 3-year and 5-year CSS rates of cervix uteri, corpus and uterus, and ovary GSs. The proportions of untreated GSs in ovary and other sites increased over years. and the proportion increased by approximately three times for other sites GSs. This may result in the decrease in 3-year and 5-year CSS rates of the other sites GS. Notably, part of the GS cases categorized as receiving no treatment may be misclassified, because the SEER database did not include first-line targeted therapy or immunotherapy.
GSs presented with worse outcomes compared to other gynecological malignancies [
9]. A study reported that patients with cervical sarcoma had the worst 5-year overall survival rate among all cervical cancer cases (63.3% for squamous cell carcinoma, 73.7% for adenocarcinoma, and 47.7% for sarcoma,
P < 0.001), and patients with cervical sarcoma had a higher risk of death compared to other patients [
2]. A study found that patients with uterine carcinosarcoma presented with higher tumor grades, a higher proportion of metastatic disease and worse survival than patients with endometrioid adenocarcinoma [
3]. A study demonstrated a dismal survival for ovarian sarcomas compared to epithelial ovarian carcinomas when matched with the same International Federation of Gynecology and Obstetrics (FIGO) stage [
4]. A study suggested that vestibular gland sarcoma grows faster and is more invasive than squamous cell carcinoma or adenoid cystic carcinoma [
30]. All the above-mentioned studies indicated that GSs were more aggressive with poorest survival among all gynecological malignancies.
This study had several limitations. First, the pathological subtypes of GSs are varied. However, because of the rare incidence, the epidemiological analysis by pathological subtypes was not performed. Second, as some important clinical features were not included in the SEER database, the prognostic factors were not adequately estimated. Third, the analysis of treatment patterns had potential bias because of the incompleteness of these two variables and undetected reasons for receiving or not receiving radiation/chemotherapy [
31]. Fourth, the SEER stage in this study changed over the study period, which may cause a bias in the analysis of stage distribution to some extent.
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