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. 2023 Apr 6;136(10):1216–1224. doi: 10.1097/CM9.0000000000002643

Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States

Rongshou Zheng 1, Hong Zhao 2, Lan An 1, Siwei Zhang 1, Ru Chen 1, Shaoming Wang 1, Kexin Sun 1, Hongmei Zeng 1, Wenqiang Wei 1,✉, Jie He 3,✉
Editor: Jing Ni
PMCID: PMC10278748  PMID: 37022941

Abstract

Background:

Neuroendocrine neoplasms (NENs) are rare tumors characterized by variable biology and delayed diagnosis. However, the nationwide epidemiology of NENs has never been reported in China. We aimed to estimate the incidence and survival statistics of NENs in China, in comparison to those in the United States during the same period.

Methods:

Based on the data from 246 population-based cancer registries covering 272.5 million people of China, we calculated age-specific incidence on NENs in 2017 and multiplied by corresponding national population to estimate the nationwide incidence in China. The data of 22 population-based cancer registries were used to estimate the trends of NENs incidence from 2000 to 2017 through the Joinpoint regression model. We used the cohort approach to analyze the 5-year age-standardized relative survival by sex, age group, and urban-rural area between 2008 and 2013, based on data from 176 high-quality cancer registries. We used data from the Surveillance, Epidemiology, and End Results (SEER) 18 program to estimate the comparable incidence and survival of NENs in the United States.

Results:

The overall age-standardized rate (ASR) of NENs incidence was lower in China (1.14 per 100,000) than in the United States (6.26 per 100,000). The most common primary sites were lungs, pancreas, stomach, and rectum in China. The ASRs of NENs incidence increased by 9.8% and 3.6% per year in China and the United States, respectively. The overall 5-year relative survival in China (36.2%) was lower than in the United States (63.9%). The 5-year relative survival was higher for female patients than male patients, and was higher in urban areas than in rural areas.

Conclusions:

The disparities in burden of NENs persist across sex, area, age group, and site in China and the United States. These findings may provide a scientific basis on prevention and control of NENs in the two countries.

Keywords: Neuroendocrine neoplasms, Incidence, Survival, Age factor, Lung, China, The United States

Introduction

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of neoplasias arising in secretory cells of the diffuse neuroendocrine systems in the body, mostly from the bronchopulmonary system and the gastrointestinal tract. They are characterized by a relatively indolent rate of growth and the ability to secrete a variety of peptide hormones and biogenic amines that cause various clinical symptoms.[1,2] The heterogeneity of NENs and their non-specific symptoms, as well as physicians' lack of awareness of these diseases, may lead to errors or delays in diagnosis.[3] While the incidence of NENs is rare, several worldwide studies have revealed increasing incidences, with more evident increases seen in countries such as the USA, Canada, and Norway.[4] In the USA, the incidence of NENs increased 6.4-fold from 1.09 per 100,000 in 1973 to 6.98 per 100,000 in 2012.[5] The incidence of NENs in Norway increased almost two-fold during two decades.[6] Due to the sharp increase in incidence and the indolent clinical behavior of the disease, the prevalence of NENs has risen eight-fold from 0.006% in 1993 to 0.048% in 2012 in the USA.[5,7,8] Therefore, NENs are now being appreciated as an emerging public health issue.

However, the nationwide epidemiology profile for NENs has never been studied in large, population-based registries with extensive long-term follow-up in China. Previous studies on epidemiology of NENs in China were limited by samples from individual or a small number of institutions, or focusing on some primary sites.[9–12] Meanwhile, China and the USA, which represent two typical but distinct countries, may show different patterns of NENs incidence and survival. A comparison of epidemiology of NENs in China and the USA may provide information for NENs prevention and control in both countries.

Therefore, this study aimed to comprehensively compare national statistics on the incidence and survival of NENs between China and the USA, based on the latest data from population-based cancer registries in China and the Surveillance, Epidemiology, and End Results (SEER) Program in the USA. These results will not only provide the disease burden of NENs in China, but also inform disparities in the epidemiology of NENs between China and the USA.

Methods

Data sources

We abstracted data on NENs in China from the database of the National Central Cancer Registry (NCCR), which is the sole national agency responsible for reporting national cancer statistics in China. NCCR collected cancer registration data from local population-based cancer registries.[13] Then we checked and evaluated the reported cancer data according to the Chinese Guideline for Cancer Registration[14] and the data quality criteria of International Agency for Research on Cancer/International Association of Cancer Registries (IARC/IACR).[15]

To evaluate the incidence of NENs in China in 2017, we used the most updated data from population-based cancer registries of China. Among 554 cancer registries that reported cancer registration data, we included 246 qualified registries reported data with NENs (116 in urban areas and 130 in rural areas), which provided a population coverage of approximately 272.5 million, about 19.5% of the national population. To assess the temporal trends in NENs incidence from 2000 to 2017, we used data from 22 high-quality cancer registries, covering about 46.6 million people. Among them, half of the cancer registries are accredited by the IARC, and the other half are certified by the NCCR.

To estimate the survival of NENs in China, we used the data from 176 qualified cancer registries that submitted data on patients diagnosed with cancer between 2008 and 2013 and followed up to December 31, 2018. All local cancer registries collected survival information based on a standardized protocol and submitted data to the NCCR.[16] Next, we checked and supplemented the patient survival information by pairing the unique ID numbers of patients to the Chinese Center for Disease Control and Prevention Cause of Death Reporting System.[17] We performed automated data-checked procedures to detect unlikely or impossible combinations, and sent them back to the registries for correction or confirmation. Finally, the proportion of cases with unknown status was 2.01%, and they were excluded from the primary analysis. We abstracted the national population data from the National Bureau of Statistics of China.[18] Local cancer registries submit respective population data to the NCCR. Each registry's population was derived from local Statistical Bureaus, Public Security Bureaus, or estimates based on national census data.

In this study, we defined NENs based on the third edition of the International Classification of Diseases for Oncology (ICD-O-3). The histology codes for NENs (8150–8157, 8240–8246, and 8249) were included. The histology codes 8002, 8040–8045, 8013, 8700, 8680, 8693, and 8510 were excluded because they represent biologically different diseases.[19] We analyzed the incidence and survival of overall NENs and their common sites, including the stomach, colon, rectum, pancreas, lung, and small intestine, which account for more than 86% of total cases.

Incidence and survival data in the USA were obtained from 18 registries using the SEER database, covering nearly 28% of the USA population (2020 submission data).[20] The age-standardized incidence of NENs was ascertained using the SEER*Stat Software version 8.4.0 (National Cancer Institute, Bethesda, MD, USA). We used SEER*Stat to generate a case listing to estimate the survival in the USA. We extracted eligible NENs records diagnosed during 2008–2013 from the SEER database according to the same criteria applied to the Chinese patients. Population mortality in the USA was provided by the National Center for Health Statistics and obtained from SEER.[21]

Statistical analysis

The crude incidence was calculated by dividing the number of new cancer cases by the corresponding number of people in a specified period. The age-standardized rate (ASR) of incidence is a weighted average of crude age-specific incidence, where the weights are the proportions of persons in the corresponding age groups based on the world Segi's population. We stratified temporal trends in incidence for NENs by calendar period (2000–2004, 2005–2009, 2010–2013, and 2014–2017), and examined the trends by fitting a log-linear Joinpoint regression models. The annual percentage change (APC) and the corresponding 95% confidence interval (95% CI) for the period were presented to estimate the magnitude and direction of incidence trends. We used the Z-test to assess whether the APC was statistically different from zero.

We calculated relative survival, the ratio of the observed survival in the group of cancer patients and the expected survival of a comparable group from the general population. Observed survival was calculated using the life-table method, and expected survival was estimated by the Ederer II method, using life tables stratified by age, sex, and calendar year. We computed the relative survival during 2008–2013 by the cohort approach, where complete follow-up was available. Relative survival was age-standardized using the International Cancer Survival Standard weights for direct comparison.[22] We calculated the relative survival in the USA with the same methods at the same periods with Chinese patients to ensure comparability. To explore the impact of cases with unknown status on the survival, sensitivity analyses were performed by assuming that patients with unknown status were either all alive or all dead. Descriptive and trend analyses were performed using SAS, version 9.4 (SAS Institute, Cary, NC, USA). Survival analyses were performed using strs in Stata, version 14.0 (Stata Corp, College Station, TX, USA). Figures were derived using R, version 4.1.2 (R Core Team, Vienna, Austria).

Results

In China, the ASR of NENs incidence was 1.14 per 100,000 in 2017. Subgroup analysis showed that the ASR of incidence was higher in males than in females (1.42 vs. 0.86 per 100,000), and was higher in rural areas than in urban areas (1.28 vs. 1.05 per 100,000). The most common primary tumor sites of NENs in China were the pancreas, stomach, lung, and rectum, constituting 33.5%, 19.7%, 15.2%, and 12.7% of the total, respectively. The incidence of NENs was significantly higher in the USA (6.26 per 100,000) than in China. The ASR of incidence was higher in females than in males (6.53 vs. 6.02 per 100,000) in the USA. The most common primary tumor sites of NENs in the USA were the lung, small intestine, colon, and rectum, constituting 19.8%, 16.6%, 15.9%, and 15.1% of the total, respectively. The incidence of NENs by primary site varied by sex and area [Table 1].

Table 1.

Incidence and proportion of NENs by sex, area, and primary tumor site in China and USA, 2017.

Site Incidence* (1/100,000) Proportion (%)
Overall Male Female Urban Rural Overall Male Female Urban Rural
China
All 1.14 1.42 0.86 1.05 1.28 100.0 61.8 38.2 52.7 47.3
Lung 0.18 0.27 0.09 0.19 0.16 15.2 18.7 9.6 18.3 11.8
Colon 0.05 0.05 0.05 0.06 0.04 4.1 3.4 5.2 4.8 3.3
Pancreas 0.36 0.42 0.29 0.28 0.49 33.5 31.2 37.1 28.2 39.3
Rectum 0.16 0.19 0.13 0.20 0.10 12.7 12.0 13.8 17.4 7.5
Small intestine 0.02 0.02 0.02 0.02 0.01 1.4 1.3 1.7 1.9 1.0
Stomach 0.21 0.29 0.13 0.14 0.33 19.7 21.8 16.5 13.9 26.3
USA
All 6.26 6.02 6.53 6.24 6.56 100.0 46.4 53.7 89.6 10.4
Lung 1.10 0.88 1.31 1.09 1.25 19.8 15.9 23.2 19.5 22.5
Colon 1.22 1.06 1.38 1.20 1.48 15.9 14.8 16.9 15.9 16.4
Pancreas 0.83 0.96 0.72 0.84 0.78 13.4 16.2 11.0 13.5 12.4
Rectum 0.99 1.03 0.96 1.01 0.74 15.1 16.6 13.8 15.5 10.7
Small intestine 0.98 1.04 0.93 0.97 1.12 16.6 17.8 15.5 16.4 18.6
Stomach 0.44 0.34 0.54 0.44 0.45 7.3 5.9 8.6 7.3 7.5
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NENs: Neuroendocrine neoplasms. *Age-adjusted incidence to the world Segi's standard population.

In general, the number of cases and incidence of NENs both climbed with increasing age until reaching a peak level, and then declined in the older age groups in both countries. The number of cases of NENs was highest at 60–64 years and the age-specific incidence was highest at 75–79 years [Figure 1].

Figure 1.

Figure 1

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Age-specific number of cases and incidence for NENs in China and the USA. NENs: Neuroendocrine neoplasms.

From 2000 to 2017, the ASR of incidence rate for NENs increased by 9.8% (95% CI: 7.1–12.6%) per year in China. Among primary NENs sites, incidence increased the most in the rectum (13.0%; 95% CI: 6.4–20.0%), followed by the lung (10.6%; 95% CI: 5.6–15.8%), the stomach (10.3%; 95% CI: 5.4–15.4%), and the small intestine (9.7%; 95% CI: 3.2–16.5%) in China. In the USA, the ASR of incidence rate for NENs increased by 3.6% (95% CI: 2.5–4.6%) per year. The incidence of NENs increased significantly in the pancreas (8.7%; 95% CI: 6.5–10.9%), followed by the stomach (4.8%; 95% CI: 3.5–6.1%), the rectum (3.1%; 95% CI: 1.0–5.3%), and the small intestine (3.1%; 95% CI: 1.6–4.6%) in the USA [Figure 2, Supplementary Table 1, http://links.lww.com/CM9/B492].

Figure 2.

Figure 2

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Trends in incidence for NENs in China and the USA, 2000–2017. NENs: Neuroendocrine neoplasms.

The overall 5-year relative survival rate in China was lower than in the USA (36.2% [95% CI: 34.5–37.9%] vs. 63.9% [95% CI: 63.2–64.5%]). The relative survival varied considerably according to the primary site, ranging from 21.5% (95% CI: 19.1–24.0%) for the pancreas to 69.8% (95% CI: 61.5–78.1%) for the rectum in China, while ranging from 52.2% (95% CI: 51.0–53.4%) for the lungs to 89.6% (95% CI: 87.5–91.7%) for the rectum in the USA [Figure 3, Table 2]. Relative survival with NENs was dependent upon both sex and area. For overall NENs, 5-year survival was higher for females than for males (43.1% vs. 31.8% in China, 67.1% vs. 60.3% in the USA). Patients with NENs in urban areas presented higher survival than patients in rural areas (39.3% vs. 30.3% in China, 64.3% vs. 60.3% in the USA) [Table 2]. Survival of NENs overall and by sites generally decreased across increasing age groups [Figure 4]. Sensitivity analysis showed that the impact of cases without a survival outcome on the relative survival was minor, with 95%CIs overlapping [Supplementary Table 2, http://links.lww.com/CM9/B492].

Figure 3.

Figure 3

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Relative survival of NENs by site in China and the USA. NENs: Neuroendocrine neoplasms.

Table 2.

Age-standardized 5-year relative survival rate of NENs by sex, area, and primary tumor site in China and USA.

Country Region Sex Prmary tumor site
All Lung Colon Pancreas Rectum Small intestine Stomach
China Overall Overall 36.2 (34.5, 37.9) 35.1 (30.2, 40.1) 62.4 (50.2, 74.5) 21.5 (19.1, 24.0) 69.8 (61.5, 78.1) 49.4 (35.7, 63.0) 29.1 (26.0, 32.3)
Overall Male 31.8 (29.7, 34.0) 30.2 (24.5, 35.9) 69.6 (47.4, 91.9) 22.0 (18.5, 25.5) 74.0 (62.9, 85.1) 48.8 (35.8, 61.9) 25.2 (21.5, 28.9)
Overall Female 43.1 (40.4, 45.9) 48.9 (39.1, 58.6) 63.2 (48.9, 77.4) 21.3 (17.8, 24.8) 61.2 (50.4, 72.0) 52.0 (27.8, 76.2) 37.3 (31.4, 43.2)
Urban Overall 39.3 (37.2, 41.3) 37.4 (31.9, 42.9) 54.6 (40.8, 68.5) 21.9 (18.8, 25.0) 76.6 (66.0, 87.1) 53.1 (36.6, 69.5) 32.0 (27.7, 36.2)
Urban Male 34.6 (32.0, 37.3) 31.3 (25.0, 37.7) 58.8 (30.8, 86.8) 22.8 (18.4, 27.2) 81.3 (68.5, 94.1) 54.5 (38.7, 70.3) 27.9 (22.9, 32.9)
Urban Female 46.4 (43.1, 49.7) 53.3 (42.4, 64.2) 51.8 (33.8, 69.8) 21.2 (16.8, 25.5) 57.0 (50.0, 63.9) 52.5 (27.9, 77.2) 39.7 (32.0, 47.3)
Rural Overall 30.3 (27.4, 33.1) 31.0 (19.9, 42.2) 81.4 (58.8, 99.9) 21.5 (17.4, 25.6) 55.8 (44.0, 67.7) 40.1 (20.4, 59.7) 24.8 (20.2, 29.3)
Rural Male 26.7 (23.1, 30.3) 30.8 (17.2, 44.5) 87.7 (74.4, 99.9) 21.7 (15.9, 27.6) 48.3 (37.3, 59.2) 43.7 (16.4, 71.0) 21.0 (15.8, 26.1)
Rural Female 36.2 (31.6, 40.7) 40.8 (19.1, 62.5) 74.2 (49.6, 98.8) 22.2 (16.3, 28.1) 59.2 (41.7, 76.7) 46.4 (22.4, 70.4) 32.7 (23.6, 41.9)
USA Overall Overall 63.9 (63.2, 64.5) 52.2 (51.0, 53.4) 63.5 (61.3, 65.7) 59.7 (57.6, 61.7) 89.6 (87.5, 91.7) 82.5 (81.1, 83.8) 75.9 (73.6, 78.2)
Overall Male 60.3 (59.3, 61.2) 39.0 (37.2, 40.8) 61.3 (58.1, 64.5) 57.9 (55.2, 60.6) 87.2 (84.0, 90.5) 82.8 (80.8, 84.8) 67.3 (63.4, 71.3)
Overall Female 67.1 (66.2, 67.9) 60.6 (59.1, 62.1) 65.3 (62.3, 68.3) 61.9 (59.0, 64.9) 91.8 (89.1, 94.6) 82.1 (80.3, 84.0) 81.4 (78.6, 84.1)
Urban Overall 64.3 (63.6, 64.9) 53.1 (51.8, 54.4) 64.2 (61.8, 66.5) 60.1 (58.0, 62.3) 89.8 (87.6, 92.0) 82.7 (81.2, 84.1) 76.2 (73.8, 78.7)
Urban Male 60.8 (59.8, 61.7) 40.0 (38.0, 41.9) 62.3 (58.8, 65.8) 58.1 (55.3, 61.0) 87.7 (84.2, 91.1) 83.2 (81.1, 85.3) 67.8 (63.5, 72.0)
Urban Female 67.4 (66.6, 68.3) 61.2 (59.6, 62.8) 65.5 (62.3, 68.8) 62.7 (59.6, 65.9) 91.8 (88.9, 94.7) 82.1 (80.1, 84.1) 81.7 (78.7, 84.6)
Rural Overall 60.3 (58.4, 62.1) 45.8 (42.3, 49.3) 58.5 (52.9, 64.2) 54.9 (49.0, 60.9) 86.8 (80.3, 93.4) 80.6 (76.8, 84.5) 73.2 (66.5, 79.9)
Rural Male 56.3 (53.6, 59.0) 32.0 (27.1, 36.9) 53.7 (46.3, 61.1) 54.4 (46.5, 62.2) 82.5 (72.8, 92.2) 79.6 (73.9, 85.4) 63.5 (52.8, 74.3)
Rural Female 64.0 (61.5, 66.5) 56.2 (51.5, 60.9) 63.9 (55.8, 72.0) 54.9 (46.0, 63.9) 91.2 (83.5, 98.8) 82.0 (76.8, 87.2) 79.5 (71.3, 87.7)
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Data are presented as rate (95% confidence interval).NENs: Neuroendocrine neoplasms.

Figure 4.

Figure 4

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Age-specific relative survival of NENs by site in China and the USA. NENs: Neuroendocrine neoplasms.

Discussion

Using the latest cancer registration data in China, we provided comprehensive information on the nationwide incidence and survival of NENs in China for the first time. Our study showed that the disparities in the burden of NENs persist across sex, area, and site in China and the USA. The incidence of NENs was lower in China than in the USA, but a more marked increase in NENs incidence was observed in China. A survival gap in NENs exists between China and the USA, with a worse prognosis in China. A better understanding of patterns and trends of the epidemiology of NENs may not only be poised to inform national policy-making, but also provide a scientific basis on the prevention and control of NENs in these two countries.

NENs comprise a broad family of neoplasms. The distribution of NENs varied among different countries or regions [Supplementary Figure 1, http://links.lww.com/CM9/B492].[23–26] In China, pancreas (33.5%), stomach (19.7%), and lung (15.2%) were the predominant primary sites of NENs, while in the USA, pulmonary (19.8%), small intestinal (16.6%), and colonic (15.9%) NENs tend to be the most prevalent. In Australia, Norway, and Canada, the most common site was the small intestine. The national geographic disparity is most likely due to environmental factors and biological differences caused by different demographics. A high proportion of NENs in the small intestine was observed in Western countries.[23–25] A previous study proposed that the low detection rate of small intestinal NENs would be responsible for the low percentage of small intestinal NENs in China.[9] However, a low proportion of small intestinal NENs is presented not only in the Chinese population,[10] but also in Asian/Pacific Islanders of America. Thus, the inconsistency is more likely due to racial and regional heterogeneity. The distribution of NENs sites was distinct within certain countries in the same region. For instance, the leading tumor sites of gastroenteropancreatic NENs in India were the pancreas and the small intestine, whereas the stomach and the pancreas were the most common sites in Greece.[27,28]

The incidence of NENs in China (1.14 per 100,000) was lower than in the USA (6.26 per 100,000) and other Western countries. In Norway, the incidence of NENs in 2010 was 21.3 per 100,000.[24] The incidence of NENs in the United Kingdom from 2013 to 2015 was 8.6 per 100,000.[29] The incidence of NENs in the Asian population was slightly lower. In Japan, the incidence of gastroenteropantral NENs in 2016 was 3.52 per 100,000.[30] These differences may be attributable to biologic factors, environmental factors, health care patterns, and/or data captured by registries.[5,19,31] A gender disparity in NENs incidence was also found in the two countries, with a higher incidence in males in China and females in the USA. The sex reversal in NENs incidence in the USA was supported by a more representative study, showing that the incidences between genders were almost similar previously, but the incidence in females (annual percent change: 11.34%) was increasing at a more rapid rate than in males (annual percent change: 8.44%) since 2013.[32] The incidence of overall NENs was higher in rural areas than in urban areas in the two countries. One study from Canada also presented a higher rural incidence as well as a similar proportion of advanced stage in rural and urban areas.[33] It concluded that the higher incidence of NENs in rural areas may be due to environmental factors, such as more chance to exposure to organochloride and organophosphate products, which have been linked to cancer-related gene mutations.[34] We also observed a high incidence of NENs in the elders, which requires more attention.

Consistent with other countries or regions,[4,23,35] the incidence of NENs increased in China and the USA over the past 18 years, with even a more rapid increase in China. The most likely reason underlying this increase is the improvements and increased implementation in diagnostic tests, particularly endoscopy, computed tomography, and magnetic resonance imaging, which resulted in the detection of asymptomatic and early stage NENs.[25] Dasari's study supported this hypothesis, showing that the increasing incidence of NENs was greater in the localized stage compared to regional stages and states of distant metastasis.[5] Consistently, the increased NENs incidence was greater for the rectum, lung, and stomach in China. The possible reason is the widespread implementation of cancer screening in China. Since 2005, the Government of China initiated a series of population-based cancer screening programs, focusing on cancers including lung, stomach, and colorectal cancers.[36] These cancer screening programs resulted in a dramatic increase in accessibility and intensity of endoscopic and imaging procedures. They further contributed to increased diagnosis of cancers as well as increased diagnosis of NENs in China. Additionally, the increased awareness of NENs among clinicians, the introduction of WHO classification for NENs, and the improved quality of cancer registration data may be partially responsible for the increase.[10] However, future research is needed to determine the exact cause.

The survival of NENs varied at different anatomic sites. In China and the USA, patients with NENs in the pancreas or the lung showed inferior survival compared to patients with the disease in other sites. The delay in diagnosis of tumor in the lung, due to failing initial treatment to improve symptoms, may result in a poor prognosis of NENs in the lung.[37] This hypothesis is supported by a global survey, indicating that 50% of patients with lung NENs were delayed in diagnosis for up to two years among 222 patients.[38] For pancreas, the majority of patients tend to be diagnosed at a later stage due to the lack of early diagnostic-specific biomarkers and symptoms.[39]

We also observed a survival gap between males and females, with female patients generally having better survival than male patients. Further analysis found that only lung and gastric NENs had a survival advantage in female patients. Several studies have shown that a high expression of estrogen and progesterone receptors was associated with a good prognosis of patients with gastroenteropancreatic NENs.[40,41] Additionally, a survival gap between urban and rural areas, with higher survival in urban areas, was presented in the two countries. It is consistent with findings from a Canadian retrospective cohort study, which found that living in rural areas and having low socioeconomic characteristics were independent prognostic factors for NENs patients.[33] Another study from the USA found that rural residence was an independent predictor of survival for NENs patients. However, the survival gap between patients with NENs in rural and urban areas disappeared after controlling for demographic, tumor, and insurance status.[42] Such a gap might be explained by healthcare-seeking behaviors, socioeconomic status, access to specialized health care, tumor biology, and environmental exposure. We also found inferior survival outcomes in elderly patients, despite taking into account the background mortality. This may be due to the more comorbidity, later stages at diagnosis, less likelihood of receiving curative treatment, and socioeconomic inequalities in elderly patients.[43] These survival gaps should be further studied based on clinical data that may explain these differences.

It deserves to be noted that the survival for NENs in China remained lower than in the USA. The survival gap may be explained in part by earlier stages at diagnosis of NENs in the USA, which indicate a better prognosis. A retrospective study conducted in China from 2001 to 2010 found that the percentages of localized NENs in gastric cardia, gastric body, and rectum were 26.6%, 32.3%, and 77.4%, respectively.[9] In the USA, the respective percentages of localized NENs in stomach and rectum were 78.9% and 93.7% (based on the SEER database), respectively. This pattern is most likely related to higher cancer screening rates and more advanced imaging technologies in the USA.[44,45] In comparison to the USA, China had a higher proportion of relatively more lethal NENs, such as pancreatic NENs, as well as a lower proportion of relatively more indolent NENs, such as colic and rectal NENs. In addition, more advanced level of treatment and management of patients with NENs in the USA may also have contributed to these results. Therefore, much work remains to be done to narrow the NENs survival gap between China and the USA. For instance, increasing further investment in medical equipment and health technology is needed. Recently, surufatinib, a novel drug developed in China, has shown a significant improvement in survival and an acceptable safety profile among patients with NENs, suggesting that surufatinib might be a novel potential treatment option.[46–48] It is hoped that the emergence and promotion of more effective treatment will improve prognosis of NENs in the two countries.

This study provides the most comprehensive information on the nationwide incidence and survival of NENs in China, based on data from 246 cancer registries, covering an approximate 272.5 million of the population, which were the largest and best available population-based estimates in China. These findings could provide a scientific basis for the prevention and control of NENs in China and the USA. However, some limitations deserve careful consideration. First, the data in our study were obtained from cancer registries, whose records only include patients with malignant NENs. Thus, this data eligibility criterion may have led to an underestimation of the actual incidence. Second, the limited population-based registries data on incidence and survival in our study cannot represent the entire general population. Nevertheless, they remain the most representative statistics in China. Finally, some information regarding NENs detailed characteristics and known prognostic indicators were not captured by the NCCR database, which is a common issue in previous studies as well.

In summary, this study provides the first comprehensive nationwide incidence and survival of NENs in China, as well as a comparison to the USA. Although the incidence of NENs was lower in China than in the USA, a significantly pronounced increase in NENs incidence was observed in China. Future studies should further explore the causes of the rise of NENs incidence and develop targeted NENs prevention and control measures. The survival gaps in NENs between China and the USA justify a pressing need to improve the understanding of NENs in order to make early diagnoses, and develop and promote effective treatments of NENs in China.

Conflicts of interest

None.

Supplementary Material

cm9-136-1216-s001.pdf (163.4KB, pdf)
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Footnotes

Rongshou Zheng and Hong Zhao contributed equally to this work.

How to cite this article: Zheng RS, Zhao H, An L, Zhang SW, Chen R, Wang SM, Sun KX, Zeng HM, Wei WQ, He J. Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States. Chin Med J 2023;136:1216–1224. doi: 10.1097/CM9.0000000000002643

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