Esophageal cancer trends in the US from 1992 to 2019 with projections to 2044 using SEER data

Simple SummaryThe incidence of esophageal cancer overall has increased in the United States, driven by increasing rates of esophageal adenocarcinoma (EAC). However, whether rates of EAC are still rising is unclear. We examined trends in esophageal cancer overall and within important sub-groups of the population. We found that esophageal squamous cell carcinoma (ESCC) rates have been steadily declining, while EAC rates rose rapidly before stabilizing in 2000. The trend of decreasing incidence of ESCC was observed almost uniformly by age group, sex, and race/ethnicity, while trends in EAC rates varied across these sub-groups. A cohort effect for EAC was observed among people born during 1950, but EAC rates were stable across successive generations born between 1950 and 1985. Given the continued rising rates of known EAC risk factors, including obesity and gastroesophageal reflux disease, there is a need to continue monitoring trends for changes in incidence rates.Background: Esophageal cancer (EC) incidence rates overall have declined in recent decades; however, the two main subtypes, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), show divergent secular trends. Methods: Age-adjusted EC incidence rates were calculated using data from the Surveillance Epidemiology and End Results (SEER) 12 Program. We examined secular trends from 1992 to 2019 overall and by age group, sex, race/ethnicity, tumor location, and SEER registry. Joinpoint regression was used to compute annual percent changes (APC) and average annual percent changes (AAPC). We used age-period-cohort models to examine the potential impact of period and birth cohort effects on trends. Results: Between 1992 and 2019, overall EC incidence rates declined by 0.54% annually (95% confidence interval [CI]: −0.75%, −0.33%). While ESCC rates declined linearly throughout the study period (AAPC = −2.85; 95%CI: −3.05%, −2.65%), EAC rates increased by over 5% annually from 1992 to 2000 (APC = 5.17; 95%CI: 3.28%, 7.10%), before stabilizing from 2000 to 2019 (APC = 0.22; 95%CI: −0.16%, 0.60%). Trends in ESCC and EAC varied by age group, sex, and race/ethnicity. Relative to ESCC rates among cohorts born circa 1950, the rates were 81% lower in cohorts born circa 1985 (rate ratio, 0.19; 95%CI: 0.04, 0.96). For EAC, rates have remained stable across successive birth cohorts since 1950. Conclusions: We observed linear declines in EC rates overall and for ESCC across age, sex, and race/ethnicity subgroups, but an inconsistent pattern for EAC. The trends in EAC cohorts born after 1955 were stable and suggest that EAC rates may have peaked in the U.S.

Introduction: Over the past thirty years, esophageal cancer (EC) incidence has been increasing more rapidly than any other solid neoplasm in the Western world. Globally, there is a large male predominance in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). The reasons for this gender difference and the possible role of estrogen remains unclear. We conducted an analytical epidemiological study to determine if estrogen exposure explains the male predominance in observed esophageal cancer incidence. Materials/Methods: We evaluated the Surveillance Epidemiology and End Results (SEER) cancer incidence trends from 1975 to 2008 using SEER Stat to calculate the annual percentage change (APC) in each five year age group and in EAC and ESCC by gender. Results: Male predominance in incidence rates of EC was most evident in the younger population and those with EAC histology as previously demonstrated. EAC and ESCC incidence rates both increases with aging, consistent with cancer being an age-related disease, but the male: female incidence ratio of EAC significantly decreased with aging. The rate of increase for EAC incidence in post menopausal females is greater than in any other demographic category. This increasing incidence rate in the post menopausal female was also observed in the ESCC, but to a lesser extent. The APC was negative (-1.5) between 1975-2008 only in the 50-64 age female cohort. Interestingly, the APC doubled in the last two age groupings of older females (age 65-74 = + 0.3 and age 75 and greater = + 0.7). APC rates for the males increased gradually in all their age groups (age 50-64 = +1.2, age 65-74 = +1.4, age 75+ = +1.9). Conclusions: The males’ incidence of EAC increases at a steep rate with aging and females’ incidence rates are not as steep except after age 60-64 where their incidence rate of change steeply increases. The steeper change in EAC incidence rates in the post menopausal female may explain why the male: female EAC incidence ratio decreases with age as seen nationally (SEER). The negative APC in the female 50-64 years age group may be explained by their peri-menopausal state and by the increased use of post-menopausal hormonal therapy since 1975 for this age group. Using age as a proxy for estrogen exposure, our findings suggest a hormonal component for the observed age-related, declining male to female EAC incidence rate ratios. It also confirms gender differences in incidence long observed in EC and suggests that the pre-menopausal estrogen milieu in females may serve as a protective factor against EAC. Moreover, this protective state dissipates with time in the post menopausal females where the effect of estrogen exposure dissipates. Implications: Our initial epidemiological observation of gender-age differences warrants translation into a molecular epidemiology study with the use of sophisticated biomarkers to establish the seemingly protective role of estrogen exposure in esophageal adenocarcinoma. Citation Format: Luckson N. Mathieu, Norma Kanarek, Craig Hooker, Malcolm Brock. Gender disparity in esophageal cancer incidence. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4802. doi:10.1158/1538-7445.AM2013-4802

Esophageal cancer (EC) consists of two main histological subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), each with distinct epidemiological patterns. Historically, ESCC has been the dominant subtype worldwide, especially in Asian countries. However, in recent decades, the incidence of EAC has been rising rapidly, particularly in European and American countries, reflecting significant shifts in global EC epidemiology. This study presents a comprehensive analysis of 25 years of high-quality continuous data on ESCC and EAC incidence trends across 25 countries. It highlights declining ESCC rates in most regions, rising EAC rates in Western nations, pronounced sex differences, and narrowing ESCC-to-EAC ratios. These diverse trends reveal the need to investigate region-specific risk factors and their contributions to the shifting burden of EC globally. The distinct trends of ESCC and EAC call for tailored public health strategies based on regional and histological patterns. Countries experiencing a rising burden of EAC or ESCC can implement targeted risk factor prevention and control measures to address the increasing trends. In clinical practice, a stronger focus on EAC in high-income countries and ESCC in regions, where it remains dominant, can improve early detection and treatment outcomes. Understanding these evolving patterns will aid in designing evidence-based interventions and optimizing resource allocation to reduce the global esophageal cancer burden effectively.

Patterns and trends in esophageal cancer incidence and mortality in China: An analysis based on cancer registry data

Trends in esophageal cancer mortality in the United States (1999-2024): Disparities by sex, race/ethnicity, region, and urbanization.

IntroductionEsophageal cancer (EC) is an aggressive malignancy with poor prognosis. Mortality and disease stage at diagnosis are important indicators of improvements in cancer prevention and control. We examined United States trends in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) mortality and stage at diagnosis by race and ethnicity.MethodsWe used Surveillance, Epidemiology, and End Results (SEER) data to identify individuals with histologically confirmed EAC and ESCC between 1 January 1992 and 31 December 2016. For both EAC and ESCC, we calculated age-adjusted mortality and the proportion presenting at each stage by race/ethnicity, sex, and year. We then calculated the annual percent change (APC) in each indicator by race/ethnicity and examined changes over time.ResultsThe study included 19,257 EAC cases and 15,162 ESCC cases. EAC mortality increased significantly overall and in non-Hispanic Whites from 1993 to 2012 and from 1993 to 2010, respectively. EAC mortality continued to rise among non-Hispanic Blacks (NHB) (APC = 1.60, p = 0.01). NHB experienced the fastest decline in ESCC mortality (APC = − 4.53, p < 0.001) yet maintained the highest mortality at the end of the study period. Proportions of late stage disease increased overall by 18.5 and 24.5 percentage points for EAC and ESCC respectively; trends varied by race/ethnicity.ConclusionWe found notable differences in trends in EAC and ESCC mortality and stage at diagnosis by race/ethnicity. Stage migration resulting from improvements in diagnosis and treatment may partially explain recent trends in disease stage at diagnosis. Future efforts should identify factors driving current esophageal cancer disparities.

Introduction: Prior studies showed that EAC had dramatically increased by 611% from 1973 to 2001. Therefore, the aim of this study was to determine the recent incidence trends of EAC by histopathology in the United States from 2000-2018 using the SEER database. Methods: Incidence rates of esophageal cancer per 100,000 population (age-adjusted to the 2000 US population) from 2000 to 2018 were calculated from the SEER 21 database using SEER*Stat software (v8.4.1, National Cancer Institute (NCI). Esophageal cancer was defined as any cancer located within the esophagus, and the histopathology subtypes were grouped as EAC or squamous cell cancer (SCC) based on ICD-O-3 Codes (Table). Time-trends reported as annual percentage change (APC) and average APC (AAPC) were quantified by Joinpoint Regression Program (v4.9.0.1, NCI), utilizing Monte Carlo permutation analysis to identify the best fit. A 2-tailed t-test was utilized to access statistical significance (p-value < 0.05). Pairwise comparison between the segmented-linear trends was performed to test parallelism and identicalness of the trends. Results: A total of 103,117 (79% male) patients were diagnosed with esophageal cancer from 2000-2018. Of those, 58,782 were diagnosed with EAC while 34,084 were diagnosed with SCC (Table). The overall incidence rate of esophageal cancer was found to be stable from 2000-2004 [APC 0.37% (95% CI, -1.32-2.07%)] but significantly decreased from 2004-2018 [APC -1.24% (95% CI, -1.48% - -1.01%)]. In SCC, the trend has shown a consistent decrease in incidence rate from 2000-2018 [APC -2.81% (95% CI, -3.03% - -2.59%)]. EAC trends showed two joinpoints. with a peak incidence noted in 2007 (Table and Figure). Despite slight variation in trends across joinpoints , the overall trend of EAC incidence was not statistically significant and therefore stable over this time period [0.61% (95% CI, -0.30% - 1.53%)], p-value = 0.19. The trends between the histopathology groups of EAC and SCC, were not identical nor parallel (p-value < 0.001), showing that the trends between these two groups differed from one another. Conclusion: While previous studies showed a >600% increase in incidence of EAC from 1973 to 2001, our updated large population-based study, covering more than a third of the US population, shows a dramatically improved stable trend from 2000 to 2018. Future studies should evaluate the impact of proton pump inhibitor use and endoscopic therapies on these trends.Figure 1.: Age-Adjusted Incidence Rates Per 100,000 Population for Esophageal Cancer A: The incidence of esophageal cancers significantly decreased [AAPC -0.89% (95% CI, -1.26%- -0.51%)] while the incidence of EAC had 3 varying segments of incidence rate: 2000 to 2008 had an increase [APC 2.13% (95% CI, 1.46% - 2.80%)], 2008-2011 had a decrease [APC -3.05% (95% CI, -8.34% - 2.54%)] and 2011 to 2018 had a stable trend [APC 0.49% (95% CI, -0.23% - 1.21%)]. B: The incidence of SCC consistently decreased [APC -2.81% (95% CI, -3.03% - -2.59%)] C: The incidence of EAC and SCC were not identical nor parallel (both p-value < 0.001). Table 1. - Incidence Trends of Esophageal Cancer in the United States by Histopathology (2000-2018) Cases n (% of N) Trends Pairwise Comparison Years APC (95% CI) AAPCa (95% CI) AAPCP-value b Test of Coincidence p-value c Test of Parallelism p-value d All Esophageal Cancer 103,117 2000 - 2004 0.37% (-1.32% - 2.07%) -0.89% (-1.26% - -0.51%) < 0.001 - - 2004 - 2018 -1.24% (-1.48% - -1.01%) Histopathology Esophageal Adenocarcinoma e 58,782 (57.0%) 2000 - 2008 2.13% (1.46% - 2.80%) 0.61% (-0.30% - 1.53%) 0.19 < 0.001 < 0.001 2008 - 2011 -3.05% (-8.34% - 2.54%) 2011 - 2018 0.49% (-0.23% - 1.21%) Squamous Cell Carcinoma f 34,084 (33.1%) 2000 - 2008 -2.81% (-3.03% - -2.59%) -2.81% (-3.03% - -2.59%) < 0.001 aAAPC is calculated as average of APCs over the time period of 2000-2008.bP-values < 0.05 were considered significant.cTests whether histopathology-specific trends were identical. P-value < 0.05 signifies the trends were not identical.dTests whether histopathology-specific trends were parallel. P-value < 0.05 signifies the trends were not equal.eICD-O-3 Codes: 8140–8141, 8143–8145, 8190–8231, 8260–8263, 8310, 8401, 8480–8490, 8550–8551, 8570–8574, 8576fICD-O-3 Codes: 8050-8078, 8083-8084

Background: Esophageal cancer (EC) is one of the deadliest cancers in the world. However, the mechanism that drives the evolution of EC is still unclear. On this basis, we identified the key genes and molecular pathways that may be related to the progression of esophageal adenocarcinoma and squamous cell carcinoma to find potential markers or therapeutic targets.Methods: GSE26886 were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) among normal samples, EA, and squamous cell carcinoma were determined using R software. Then, potential functions of DEGs were determined using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The STRING software was used to identify the most important modules in the protein–protein interaction (PPI) network. The expression levels of hub genes were confirmed using UALCAN database. Kaplan–Meier plotters were used to confirm the correlation between hub genes and outcomes in EC.Results: In this study, we identified 1,098 genes induced in esophageal adenocarcinoma (EA) and esophageal squamous cell carcinoma (ESCC), and 669 genes were reduced in EA and ESCC, suggesting that these genes may play an important role in the occurrence and development of EC tumors. Bioinformatics analysis showed that these genes were involved in cell cycle regulation and p53 and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. In addition, we identified 147 induced genes and 130 reduced genes differentially expressed in EA and ESCC. The expression of ESCC in the EA group was different from that in the control group. By PPI network analysis, we identified 10 hub genes, including GNAQ, RGS5, MAPK1, ATP1B1, HADHA, HSDL2, SLC25A20, ACOX1, SCP2, and NLN. TCGA validation showed that these genes were present in the dysfunctional samples between EC and normal samples and between EA and ESCC. Kaplan–Meier analysis showed that MAPK1, ACOX1, SCP2, and NLN were associated with overall survival in patients with ESCC and EA.Conclusions: In this study, we identified a series of DEGs between EC and normal samples and between EA and ESCC samples. We also identified 10 key genes involved in the EC process. We believe that this study may provide a new biomarker for the prognosis of EA and ESCC.

It is important to note that although the current treatment for advanced esophageal cancer (EC) has made great technological advances, patients' 5-year survival rates do not appear to be encouraging. Therefore, understanding the clinicopathological features and metastasis patterns of the patients with stage IV EC, combined with the prognosis of these patients, can aid in choosing the optimal treatment plan. It is well known that esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two most common pathological types. The aim of this study is to examine and compare the clinicopathological features and metastatic modes of stage IV ESCC and EAC, as well as their prognosis and survival. Based on the Surveillance, Epidemiology, and End Results (SEER) database, we assessed the characteristics of ESCCs and EACs associated with prognosis using the Kaplan-Meier survival analysis, and the Cox regression model. Furthermore, the clinical data of 217 patients with stage IV ESCC and EAC in the Department of Gastroenterology of the Second Affiliated Hospital of Nantong University between 2014 and 2016 were reviewed. A total of 3,707 cases treated between 2010 and 2016 were included. The incidence of EAC in the United States is much higher than that of ESCC. Common metastasis patterns were lungs only, liver only, bones only, and lung & liver. The multivariate Cox analysis showed that treatment mode and metastasis patterns were independent risk factors affecting the overall survival (OS) time of patients (stage IV ESCC & EAC). EAC patients with only lung metastases may have a longer survival if chose treatment options that included surgery. In the external cohort, a total of 217 cases were included. The prevalence of ESCC is much higher than that of EAC, and the common metastasis patterns are liver only, lung only, and liver & lung. The multivariate Cox analysis showed that treatment mode was independent risk factor affecting the OS time of patients (stage IV ESCC & EAC). EAC patients treated with surgery combined with chemoradiotherapy may have a better prognosis. In general, the prognosis of patients with stage IV ESCC and EAC are poor. However, surgery was found to significantly improve the OS time of patients with stage IV EAC in this study.

Introduction: While endoscopic resection followed by ablation has become the preferred approach for select superficial esophageal adenocarcinomas, the epidemiology of early stage disease has not been examined. This was evaluated in the context of the overall incidence and the rate of change relative to the other major epithelial cancers. Methods: The Surveillance Epidemiology and End Results (SEER) data from 1973 to 2014 were analyzed to compare age-adjusted incidence rates among major epithelial carcinomas including esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma, breast, prostate, pancreatic, lung, colorectal, and gastric cancer. The percent change in incidence over time was compared by tumor subtype. The fraction of early T-stage, node-negative EAC without metastasis was examined from 2004 to 2014, when precise T-stage data was available. Results: There were 17,026 patients with esophageal adenocarcinoma, 85% of whom were men, 92.0% non-Hispanic White, and 73.3% above the age of 60. Of these, 745 patients were in the early stage analysis cohort. The change in the annual incidence from 1973 to 2014 was 733% for EAC. By Joinpoint analysis, the average annual percent change (AAPC) of esophageal adenocarcinoma during this time period was 5.4% (95% CI 4.8, 6.1). The increase in EAC incidence was significantly higher than for other epithelial malignancies over the same time period (p-value < 0.05). The next most rapidly increasing malignancy examined was breast cancer, which had an AAPC of 0.9% (95% CI 0.4, 1.3). The annual percent change plateaued between 2004 and 2014, and the fraction of cases of early stage disease remained stably high at 21%. Conclusion: Over the past four decades, there has been a 7-fold increase in the incidence of esophageal adenocarcinoma, significantly greater than that observed in other major epithelial malignancies. Approximately one in five patients appear to have potentially resectable early stage disease and may be eligible for organ-sparing, minimally invasive management. Further studies may clarify the cause of the disproportionate increase in esophageal adenocarcinoma relative to stable or decreasing rates in the other tumor subtypes, but overall, this study supports the proliferation of treatment options and increasing focus on the prevention, detection, and treatment for early stage esophageal adenocarcinomas.333_A Figure 1. Percent Change in Annual Incidence of Major Epithelial Cancers from 1973- 2014 Relative to the Index Year, by Cancer Type333_B Figure 2. Annual Incidence Rate of Early Stage Esophageal Adenocarcinoma 2004- 2014333_C Figure 3. Cases of Esophageal Adenocarcinoma 2010-2014, by Tumor Stage

BackgroundThis study explored the global burden of esophageal cancer mortality and temporal trends, with a focus on premature populations aged 30-69 years.MethodsEsophageal cancer mortality data for premature populations was extracted...

AGA Clinical Practice Update on the Utility of Endoscopic Submucosal Dissection in T1b Esophageal Cancer: Expert Review

Low Incidence of Esophageal Adenocarcinoma After Eradication of Helicobacter pylori in Japan

Background Esophageal cancer continues to pose a significant public health challenge worldwide. However, the extent to which advancements in treatment have reduced mortality at the population level remains unclear. This study examines trends in esophageal cancer mortality in the United States from 1999 to 2023, focusing on variations based on sex, ethnicity, urbanization level, census region, and age group. Methods Mortality data were obtained from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database using ICD-10 codes (C15.0–C15.9) to identify esophageal cancer-related deaths. The analysis included individuals aged 25 years and older. Temporal trends in age-adjusted mortality rates (AAMR) were analyzed using the Joinpoint Regression Program. Data were stratified by census region, metropolitan/non-metropolitan residence, and state. Annual percentage change (APC) and average annual percentage change (AAPC) were calculated along with their 95% confidence intervals (CI). Results Between 1999 and 2023, a total of 357,606 deaths from esophageal cancer were recorded. A significant decline in the mortality rate was observed over this period, with the overall AAMR decreasing from 6.74 to 5.61 per 100,000, corresponding to an AAPC of −0.81* (* p -value &amp;lt; 0.05). Decline in the mortality rate was evident across nearly all ethnic groups, with the exception of the non-Hispanic (NH) white group. The most significant reduction was observed among non-Hispanic Black individuals (AAPC: −4.07*). Significant sex-based disparities persisted throughout the study period, with men consistently experiencing higher mortality rates than women. Geographically, mortality trends diverged: metropolitan areas experienced a significant decline (AAPC: −1.09*), whereas non-metropolitan areas experienced a significant increase (AAPC: 0.48*). Pronounced regional disparities were also noted, with the western and northeastern regions demonstrating the most substantial improvements. Age-specific analyses revealed a significant reduction in the mortality rate across the majority of age groups; however, among adults aged 85 years and older, the mortality rates remained stable. Conclusion Despite an overall decline in the mortality rate of esophageal cancer, significant disparities persist across geographic, urban–rural, and age subgroups. These findings highlight the need for targeted public health interventions to address ongoing inequalities, particularly among NH white individuals, those living in non-metropolitan areas, and older adult.

In Western populations, the incidence of oesophageal squamous cell carcinoma (OSCC) has been declining, whereas the incidence of oesophageal adenocarcinoma (OAC) has been increasing. Our study examines temporal trends in the incidence of oesophageal cancer in the Netherlands between 1989 and 2016, in addition to predicting future trends through 2041. Data from the Netherlands Cancer Registry and Statistics Netherlands were collected to obtain incidence trends of OSCC and OAC for the period 1989 to 2016. Age‐period‐cohort (APC) modelling was used to estimate the contribution of age, calendar period and birth cohort on the observed incidence trends. To predict the future numbers of new cases of both OSCC and OAC from 2017 to 2041, log‐linear APC models were fitted to the trends of 1989 to 2016. The age‐standardised incidence rates of OSCC have decreased slightly for men and increased slightly for women. In contrast, a marked increase in the incidence of OAC was observed, ranging from 2.8 per 100 000 persons in 1989 to 10.1 in 2016. This increase in OAC incidence was more prominent in men, and it will result in an increased risk of OAC for successive generations. Future projections indicate that the incidence of OAC will further increase to 13.1 per 100 000 persons in 2037 to 2041, meaning that there will be 13 259 cases of OAC in 2037 to 2041, as compared to 9386 diagnoses in 2017 to 2021. The changing epidemiologic trends in oesophageal cancer in the Netherlands should be reflected in the development of prevention, early detection and treatment strategies.