August 11, 2022

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Researches on “precise screening” of esophageal cancer

Researches on “precise screening” of esophageal cancer



 

Researches on “precise screening” of esophageal cancer.

Esophageal cancer refers specifically to malignant tumors that originate from the epithelium of the esophagus, which can be divided into two subtypes: esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), which are related to tissue origin, genetic changes, etiology and treatment There are clear differences in prognosis.

 

Like most other tumors, the occurrence and development of esophageal squamous cell carcinoma is a complex causal multi-stage process, which can be roughly divided into the etiological exposure period, preclinical period (asymptomatic and mild period), clinical period (significant symptom period) and prognosis There are multiple stages including the vesting period.

 

Over the past half a century, relevant scholars have carried out a series of population epidemiological and etiological studies in areas with high incidence of esophageal squamous cell carcinoma in China, reporting risk factors in multiple dimensions including environmental exposure and genetic susceptibility, but so far they have not been able to It is clear that the main cause of the high incidence of esophageal squamous cell carcinoma in China, the primary prevention of esophageal squamous cell carcinoma, that is, the etiological prevention, lacks intervention targets.

 

 

Secondary prevention, which is commonly referred to as “screening”, “screening” or “early diagnosis and early treatment” has become the main form of prevention and treatment of esophageal squamous cell carcinoma in China. Targeted early screening of people with mild disease is to find out who are in the early stage of esophageal malignant lesions (such as severe dysplasia, carcinoma in situ) or precancerous lesions with the potential for malignant transformation (such as mild and moderate atypia) Hyperplasia) individuals should undergo timely and effective clinical treatment (such as endoscopic treatment, surgical treatment, endoscopic follow-up monitoring, etc.), so as to change the natural progression of the disease, reduce or even avoid the occurrence of advanced esophageal squamous cell carcinoma and related deaths The ultimate goal.

 

Early screening of people with esophageal squamous cell carcinoma in China began in the high-risk areas such as Linxian County, Henan Province in the 1960s. A large number of cancer prevention and treatment workers are engaged in high-risk screening and related scientific research.

 

With the continuous advancement of work, the state has also invested further resources to continuously pay attention to the large-scale development of early diagnosis and treatment of tumors including esophageal squamous cell carcinoma, and initiated major public health projects including the “Taihang Project” and “central transfer payment for local tumor prevention A series of national cancer population screening programs such as the “Project” and the “Huaihe River Basin Cancer Early Diagnosis and Treatment Project”.

 

By the end of 2018, a total of more than 2.16 million upper gastrointestinal endoscopy screenings had been completed at 194 project sites nationwide, and more than 34,000 patients with malignant esophageal diseases were found, of which the early diagnosis rate reached more than 70%. The above work has played an important role in the prevention and treatment of major malignant tumors in China, including esophageal squamous cell carcinoma, and has accumulated rich experience in the organization and implementation of population prevention and treatment projects.

 

However, as the concept of “Evidence-based & Value-based Medicine” continues to deepen, looking at the historical process and development of the early diagnosis and treatment of esophageal squamous cell carcinoma in China, the The screening model of esophageal squamous cell carcinoma has encountered clear development bottlenecks in the following aspects, and it is urgent to carry out corresponding basic and applied translational research to make breakthroughs.

 

 


1. The effect and health economic value of endoscopic screening for esophageal squamous cell carcinoma need to be supported by evidence from a “randomized controlled study”

Endoscopic screening for esophageal squamous cell carcinoma is not only directly economical and costly, but also the collateral damage it brings cannot be ignored. This includes complications such as “bleeding”, “perforation”, and “iodine allergy” caused by routine endoscopy. It also includes unnecessary psychological pressure caused by false positive screening results to the examinee, and even discrimination from the surrounding environment.

This requires that two important questions must be answered before formulating and recommending the “Guidelines for Screening Esophageal Squamous Cell Carcinoma” to the public: One is “Effectiveness”, that is, whether “early detection and treatment” is true from a group perspective It can change the natural course of the disease and reduce the risk of advanced esophageal squamous cell carcinoma and related deaths; the second is “cost-effectiveness”, that is, the need to carry out “health economics evaluation” to clarify that under specific health resource allocation conditions , Whether large-scale population screening conforms to the principles of health economics and which screening model is more cost-effective and effective.

In terms of population screening effects, a number of large-scale prospective population cohort studies in China have reported the protective effect of early endoscopic screening on reducing the clinical incidence and related deaths of esophageal squamous cell carcinoma. However, limited by the design limitations of observational studies, even large multicenter cohort studies with long-term follow-up still cannot avoid “Lead time bias”, “Length time bias” and “Confusion” “Confounding bias”. The existence of the three major biases cannot rely on “comparing the overall outcome risk or survival level between the screening case and the naturally diagnosed case or the screening group and the non-random control group” to prove the screening effect. In the field of screening effect evaluation, the only research design that can effectively circumvent the above-mentioned problems is the “Population-based randomized controlled trial (RCT)”.

Through long-term prospective follow-up, the overall rate of outcome events in the “screening group” (such as the incidence of advanced esophageal squamous cell carcinoma and the death cause-specific mortality rate of esophageal squamous cell carcinoma) is assessed as a whole to be lower than the overall level of the “randomized control group”. Check whether it is effective to provide the highest level of evidence-based medicine evidence. Although this type of research design is difficult to implement, it is a necessary condition for a screening strategy to eventually be written into the guidelines and recommended to the public health and clinical medicine fields. In the American Cancer Society (ACS) tumor screening guidelines, the screening strategies for cervical cancer, lung cancer, colorectal cancer and breast cancer recommended to the world are all based on the evaluation results of large randomized controlled studies.

Similarly, because the results of randomized controlled studies do not support effective or controversial screening, a series of familiar tumor screening programs have gradually withdrawn from the stage of history or lowered their recommendation levels, such as X-ray screening for lung cancer, vaginal ultrasound and CA125 Screening for ovarian cancer, PSA screening for prostate cancer, etc. For this reason, the Cochrane Library also published a systematic review, proposing that “randomized controlled studies are urgently needed to avoid the influence of lead time bias and other effects so as to provide the final scientific conclusion on the screening effect of esophageal squamous cell carcinoma.”

Similarly, due to the high-quality control group setting in the population randomized controlled study and the screening practice closer to the real world, this design is also the best choice for scientific evaluation of the health economic value of screening. Combining the screening effect with the basic socio-economic conditions of the population where the screening work is performed, and deriving the optimal screening strategy under the existing resource supply conditions, is direct evidence to ensure the feasibility of the population tumor screening program.

In 2012, our research group initiated the “Randomized Controlled Study of Population Evaluating the Effect and Health Economic Value of Endoscopic Screening for Esophageal Cancer” (Endoscopic Screening for Esophageal Cancer in China, “ESECC” trial; Clinicaltrials: NCT 01688908). The study used a cluster random method to randomly select 668 natural villages in a county in the high-risk area and randomly divide them into a screening group and a control group (334 villages/groups). The screening group was screened by standard iodine staining endoscopy.

The control group is not screened. It is planned to compare the incidence of advanced esophageal squamous cell carcinoma, death cause-specific mortality, all-cause mortality, cost-effectiveness, cost-utility and other health economic indicators through follow-up for more than ten years. Draw important conclusions about whether the screening is effective or not and whether it is economical. The randomized controlled study design is difficult to implement, and the longitudinal follow-up time is long. The study is still in the follow-up stage and no final results have been obtained. Therefore, the widespread screening of esophageal squamous cell carcinoma in China has not been able to write high-level evidence into the international tumor screening guidelines for clinical and public health first-line recommendations.

Considering the invasiveness of the screening technology for esophageal squamous cell carcinoma and the existence of subsequent risks, the current academic community recommends to the general public for early endoscopic screening of esophageal squamous cell carcinoma should also be relatively cautious.

 

 


2. It is necessary to change the traditional screening and monitoring plan, and establish a “precise screening model based on individual risk prediction”

Even though the epidemiological studies of high-standard design prove to be effective and economical, the “whole population” screening strategy that we have been using for decades has come to make changes. This is because:

First of all, as mentioned above, screening for esophageal squamous cell carcinoma requires a lot of direct and indirect “costs.” Although the value of life is constantly being emphasized today, this is often overlooked by people, but to carry out a group-level screening for esophageal squamous cell carcinoma requires a lot of resources or even considerable “collateral damage” to be realized.

More importantly, in the real world, the “consequences” of screening often have large human heterogeneity, that is, even if the same technology and standard are used to screen for the same disease, different individuals There may still be significant differences in the effects, and even different in nature. In other words, the same screening may have a good protective effect for some people, while it is not effective, ineffective or even harmful for another subgroup of people. For example, in reality, there are some patients with precancerous lesions of esophageal squamous cell carcinoma (even high-grade lesions such as moderate and severe dysplasia). They will not progress to cancer for a long time, and they will only stay for the whole life. In the stage of precancerous lesions, these patients cannot benefit from early endoscopic diagnosis and follow-up clinical treatment at all, and may even cause serious damage to their physical and mental health and quality of life due to additional diagnosis and treatment. The above-mentioned heterogeneity also exists even in high-incidence areas.

A recent large-scale screening cohort follow-up study conducted in a high-incidence area in China showed that among more than 20,000 asymptomatic participants from natural populations, up to 73.7% of them were found to have had symptoms during baseline endoscopic screening. Microscopic mucosal tissue biopsy is performed for iodine staining lesions (LULs), but the detection rate of patients with severe dysplasia and above (requiring immediate clinical treatment) is less than 3%, which means that 97% of the subjects cannot understand the current situation. Benefit from mirror screening.

During the follow-up period of more than 8 years, only 1.4% and 4.5% of patients with mild and moderate dysplasia undergoing regular endoscopic monitoring and review eventually progressed to esophageal squamous cell carcinoma, which suggests that more than 95% of patients undergo review Subject does not benefit from repeated endoscopic monitoring. Another follow-up study carried out in an adjacent high-risk area further revealed that the problem of “underdiagnosis” also exists compared to the aforementioned “over-screening and monitoring”.

During the median follow-up period of 4 years after the initial screening, up to 40% to 50% of patients with newly-occurring esophageal malignancies were not detected as precancerous lesions of dysplasia during the initial endoscopic screening. Excluded from the endoscope monitoring plan, thereby losing the opportunity to be protected. If the baseline screening and malignant lesions of the esophagus diagnosed within 1 year after the screening are regarded as “true positive”, the sensitivity of the initial endoscopic screening in the above two studies is almost the same (96.0% vs. 96.5%).

The above results clearly indicate that the traditional screening model of “whole population participation + follow-up monitoring plan based only on pathological diagnosis” carried out in high-risk areas of esophageal squamous cell carcinoma in China has encountered a development bottleneck: two key roles in screening work — “Endoscopes” and “pathologists” have reached the upper limit of their working ability under the current technical standards and screening modes. In the process of observation under the microscope, it is impossible to accurately distinguish which lesions should be examined. At the same time, only pathological diagnosis cannot accurately predict which patients are high-risk lesions and should undergo endoscopic monitoring.

This leads to a large number of invalid biopsies in the initial screening and a high proportion of invalid endoscopic follow-ups after the screening. In addition to the waste of resources, it will inevitably bring about direct and indirect damages related to various screening. Therefore, the screening of esophageal squamous cell carcinoma in China urgently needs to undergo a model change, scientific research to guide practice, and to formulate “precise screening strategies” to improve the overall cost-effectiveness of large-scale screening and reduce the risk of damage. The overall idea of ​​the “precise screening strategy” is to “through individualized risk prediction and classification, to maximize the elimination of low-benefit groups from screening and review, and to improve the overall screening effect while reducing resource input and collateral damage, and finally achieve’ “The overall goal of reducing costs and increasing efficiency” can include the following three stages according to different entry points:

 

First, conduct risk assessment of esophageal squamous cell carcinoma among the general population, accurately identify individuals or sub-populations at high risk, and implement endoscopic screening for only this sub-population to achieve the enrichment of high-risk populations before screening and reduce initial screening Increase the detection rate of malignant lesions while increasing the workload;

 

Then, in order to improve the accuracy of endoscopic biopsy, that is, to reduce the “unnecessary biopsy” and “missed inspections” caused by lack of experience and irregular operation, the massive endoscopic iodine stained images in reality screening practice can be used Development of computer-aided diagnosis system. In the process of establishing this system, all malignant and precancerous lesions detected during initial screening and malignant lesions that occurred during a specific follow-up period should be used as predicted outcome events. The system should be deeply integrated with the endoscopic operation and graphic reporting system, so as to dynamically display the predicted probability of different pathological diagnosis levels of unstained lesions during the endoscopic examination. For example, severe dysplasia and above lesions (90%), mild and moderate dysplasia (6%), and non-dysplasia lesions (4%), indicating that the 90% probability is severe dysplasia and above lesions, 6% The probability is mild and moderate dysplasia, 4% probability is non-dysplasia benign lesions. This will help the endoscopist quickly decide whether to perform a biopsy.

Finally, for patients with abnormal changes in the esophageal mucosa found during screening, a multi-dimensional comprehensive progression risk assessment will be performed again, and intensive endoscopic follow-up will be conducted for patients with high risk of progression, and low-risk patients will adopt a loose review plan or not undergo endoscopic review , To achieve individualized monitoring after screening.

For multi-cause and single-effect diseases such as malignant tumors, the etiology network is complex and the population heterogeneity is obvious. Risk prediction and evaluation cannot continue to use the “risk factor” research design that emphasizes the independent role of single factors. Instead, multiple factors should be combined to build an integrated risk prediction model. The comprehensive evaluation of risk is not only the main development path for the prevention and control of esophageal squamous cell carcinoma and other malignant tumors to become more precise and intensified, but also the key to the implementation and transformation of precision medicine in the field of tumor screening in the future.

Based on the above-mentioned basic ideas, based on the large-scale high-incidence area population screening cohort (“ESECC” cohort) 15,000 cases of endoscopic screening results and long-term longitudinal follow-up data, the research group established a “esophageal malignant disease prevalence” that fits the characteristics of the Chinese population. “Risk prediction model” and “risk prediction model for the progression of precancerous lesions of the esophagus”. The evaluation shows that the prevalence prediction model is used to concentrate the high-risk population of subjects before the initial screening, and as many as 20% of endoscopy can be avoided under the premise of 100% sensitivity; and the disease progression risk prediction model is applied after screening.

 

It can greatly increase the prediction accuracy of precancerous lesions into malignant lesions from 70% of the existing pathological diagnosis alone to nearly 90%. It can also protect 40% to 50% of advanced cases, breaking the “ceiling” of the traditional model. Clearly improve the overall protective effect of screening. After that, we further evaluated the early warning effect of “endoscopic iodine staining abnormal features” on the risk of early esophageal squamous cell carcinoma progression, and proved that “size of LULs” in the early warning of esophageal disease progression risk And put forward that “comprehensive risk grading and endoscopic monitoring should be carried out for’patients with lesions not reaching the grade of dysplasia’ combined with endoscopic iodine staining, and should not be excluded from the endoscopic review plan as a whole”, and In this way, a “new plan for early endoscopic monitoring of lesions after screening” is proposed. Analysis shows that this monitoring program makes up for the lack of pathological diagnosis capabilities, and reduces the proportion of missed cases due to failure to review in time among the esophageal squamous cell carcinoma cases that occurred during the follow-up period by 65.3%.

 

This series of research work has achieved “enrichment of high-risk populations before endoscopic screening” and “individualized endoscopic monitoring after screening”, and has developed and monitored the “whole population screening” and “pathological diagnosis alone” currently adopted in China. The traditional model of “Program” has been innovated. The risk prediction model and new endoscopic monitoring program developed are simple, easy to use, scientific and reliable, and are the most systematic and complete accurate risk grading tools in the field of esophageal squamous cell carcinoma screening inChina. With this as the core, the theoretical framework and evidence system of the “precise prevention and treatment strategy for esophageal squamous cell carcinoma” that are in line with the actual situation inChinas high-risk areas have been initially established, which has important public health significance and clinical application value.

Researches on "precise screening" of esophageal cancer

 

 


3. A deeper understanding of the important and special value of “clinical opportunistic screening” in the prevention and control of esophageal squamous cell carcinoma in China

In the field of cancer screening, according to different decision-making, implementation and cost payment subjects, screening can be divided into “policy or project-driven organized screening (Organized screening)” and “clinical opportunistic screening jointly decided by doctors and patients.” (Opportunistic screening)”. Organized population screening is an active screening project initiated by relevant government departments and medical service institutions, and funded by the government, medical institutions and medical expense payers (such as the medical insurance system) individually or jointly. The subjects are recruited from ordinary communities. For the asymptomatic population, the screening program and the definition of the target population have clear and uniform standards, and the subject only needs to bear a small inspection fee or even free. This screening mode has good overall planning, high degree of standardization, and is easy to carry out strict quality control and evaluation. However, organized population screening requires continuous investment in a large amount of human and material resources, and it is difficult to promote and continue on a large scale.

 

With the continuous improvement of public health awareness, accessibility and quality of medical services, clinical-based opportunistic screening has gradually attracted attention. “Clinical opportunistic screening” refers to a targeted treatment conducted by both doctors and patients based on the risk assessment results, the patient’s socio-economic capabilities and willingness when a high-risk object of a certain disease sees a doctor for any reason. Sexual screening. The subjects of opportunistic screening are more proactive in screening, and because the subjects are mostly “high-risk objects” of the disease, the proportion of disease detection is significantly higher than that of the general population, so it is more cost-effective . In addition, the cost of opportunistic screening is mainly borne by the examinee and medical insurance, so that the cost of screening is reduced to zero, which is conducive to continuous promotion on a larger scale.

 

In the traditional epidemiological concept, when the symptoms or signs of the disease have not yet appeared, active inspections for early detection of the disease are called “screening tests.” In contrast, the confirmatory test performed to confirm the diagnosis and give treatment after the appearance of disease-related symptoms or signs is called a “diagnostic test.” Screening tests can usually change or even block the natural course of the disease through clinical intervention at an earlier stage of the disease, so as to delay or avoid the occurrence of adverse disease outcomes. The classic diagnostic tests mostly belong to the category of clinical work, and the discovered disease stages are the distribution state under natural conditions. In the traditional definition, the two have a relatively clear boundary, that is, “whether symptoms have occurred”. With the continuous development of medical technology and screening practice, the boundaries between the two sometimes become blurred.

 

From the perspective of time, the appearance of disease-related symptoms of a disease is usually a gradual and continuous process, and it cannot be simply differentiated into “with” and “without.” After symptoms appear (even if it is a very mild symptom), whether to receive the corresponding clinical examination is not only related to the patient’s own medical awareness, socioeconomic ability and other personal factors, but also heavily dependent on external factors such as medical service accessibility and service level . With the improvement of medical technology and the ability and awareness of patients to seek medical treatment, clinical-based “screening test”, also known as “clinical opportunistic screening”, emerged and gradually attracted attention.

 

As some clinical outpatients may have mild symptoms, the disease stage may be later than the screening of asymptomatic people in the aforementioned community. However, if they can receive clinical risk assessment and active referral in opportunistic screening under the guidance of doctors, it is equivalent to Lowering the threshold for patients to see a doctor on their own can achieve early disease diagnosis to a certain extent. The direct result of this “advanced diagnosis” is the advancement of the stage of the disease at the time of diagnosis, also known as “downstaging”. Therefore, clinical opportunistic screening has the characteristics of both screening test and clinical diagnostic test at the “intervention time point”. In addition, from the perspective of screening technology, upper gastrointestinal endoscopy has both “screening” and “diagnostic” attributes. An upper gastrointestinal endoscopy can simultaneously conduct a comprehensive inspection of the malignant lesions of the esophagus, cardia, stomach and duodenum, and perform immediate biopsy and histopathological diagnosis of abnormal mucosa.

 

Not only has it achieved “multi-disease simultaneous combined screening”, but also because pathological diagnosis is the gold standard technology for malignant tumor diagnosis, the upper gastrointestinal endoscopy screening work has achieved the integration of screening tests and diagnostic tests.

 

In China, although a large number of community-based organized population screening projects have been carried out, and human and material resources have been invested heavily, they can only cover a few areas, and there is a huge gap compared with the huge screening needs of the country. If the coverage of screening is expanded with the current model, and to achieve the important core indicator of “reducing the premature mortality of major chronic diseases” proposed in the “Healthy China 2030” Plan, it is estimated that upper gastrointestinal endoscopy is needed every year across the country. About 120 million cases were screened. From the current national material and financial resources, as well as the number and ability of existing professional and technical personnel, it is extremely difficult. In this case, the emergence of the “clinical opportunistic screening” model provides a solution to this problem.

 

Most patients with esophageal squamous cell carcinoma are in the middle and advanced stages when they see a doctor, and the prognosis is poor. An important reason that cannot be ignored is the failure of timely diagnosis and treatment after the symptoms appear. In our country, especially in the high-incidence areas in rural areas, patients are limited by relatively backward socio-economic levels and weak health awareness, and often do not seek medical services until the symptoms of esophageal obstruction are obvious, thus delaying the timing of diagnosis and treatment. In addition, the upper gastrointestinal symptoms are complex and lack specificity. In the absence of effective and easy-to-use risk assessment tools, it is difficult for clinicians to make accurate endoscopic referrals. Therefore, it is an important goal of clinical opportunistic screening for esophageal squamous cell carcinoma in China to prompt patients who are asymptomatic or have mild symptoms to “see a doctor in advance and diagnose in advance” to achieve downgrading, especially for esophageal squamous cell carcinoma in poor rural areas in China. The value of high-incidence areas is more important.

 

For opportunistic screening, the following key points need attention: 1) Like organized population screening, clinical opportunistic screening must also be based on the evidence base of “effective screening” of high-standard evidence-based medicine To ensure that screening can benefit early patients; 2) Accurate, reliable, simple and easy risk assessment is an important prerequisite for the implementation of opportunistic screening, so as to achieve accurate referrals and avoid overburdening relevant institutions and medical treatment. Waste of resources; 3) Unite with primary medical institutions to form a fixed cooperative alliance and screening work network for specific screening targets and disease types, and provide targeted opportunistic screening training and screening for outpatient physicians of relevant professions in each member unit Supervision, improving its risk assessment capabilities, and realizing mutual recognition of screening results are an ideal model for the promotion of opportunistic screening at the grassroots level.

 

This research group established a cohort based on two central medical institutions in the high- and low-incidence areas in the north and south, collected data on risk factors related to esophageal squamous cell carcinoma of more than 10,000 patients in endoscopic outpatient clinics, combined with endoscopic biopsy pathological diagnosis results, and constructed the first A risk prediction model for esophageal malignant lesions suitable for clinical opportunistic screening and proposed risk classification standards. After evaluation, in the northern high-risk population data set, the model has an accuracy of 87.1% in predicting malignant esophageal lesions. In the non-high-incidence area in the south of the mixed population with strong heterogeneity (covering 30 provinces and autonomous regions in China), the model The prediction accuracy rate is still as high as 84.3%. This research has realized the individualized risk assessment necessary for the “Clinical Opportunistic Screening of Esophageal Squamous Cell Carcinoma”, and provided the necessary prerequisites for the establishment and promotion of opportunistic screening for esophageal squamous cell carcinoma in China.

 

In fact, whether it is “organized community screening” or “clinical-based opportunistic screening”, the main body of implementation is still limited to external forces such as the government, research and clinical medical institutions, rather than the screened person himself. That is, as long as those individuals who should be screened do not have “subjective motivation” to participate in or accept the corresponding screening mobilization and recommendations, they will still not be covered by the screening work. Therefore, in terms of audience coverage, even if the two screening methods are combined, they can only cover a part of the entire target population, or even only a small part. The key to solving this problem is to motivate individuals who should be screened to “actively” seek screening services to the greatest extent possible, thereby increasing the coverage of the target population.

 

This is also the basis for realizing that a disease screening work can truly gain population protection and reduce the end-stage morbidity and mortality of the disease as a whole. Relying on the mobile Internet and self-media social platforms to build and promote easy-to-use “online risk assessment tools”, so that the public can easily conduct self-assessment and self-assessment of disease risks, and provide graphical assessment results with a friendly interactive interface based on statistical data And screening recommendations are an important way to solve this problem. In the era of big data and mobile internet, the emergence of this model is bound to bring new dawn to the precise screening of major chronic diseases such as esophageal squamous cell carcinoma.

 

 


4. Outlook

The implementation of a population-level cancer screening program requires a huge investment of resources, and the audience involved is also very wide. The intrusiveness of the screening technology itself and the limitations of its protective effectiveness and other negative effects that follow will have a huge impact on the safety of the screening plan, clinical effects and even the physical and mental health of the subject. The key How to find the best balance between benefit and potential harm. Among them, the first thing to emphasize is that all cancer screening recommendations made to the public must be based on high-profile populations or clinical epidemiological evidence. Among them, randomized controlled trials are still an insurmountable design type.

 

Of course, it is not entirely necessary to obtain evidence from a randomized controlled study before screening can be recommended. If there are high-quality prospective observational studies, professional tips can also be given, but the level of recommendation must be lowered accordingly. In addition, because the absolute prevalence of cancer is not high, and the screening methods are more invasive, the psychological pressure brought by a positive diagnosis result is huge, and the medical and health resources available for this work are also quite scarce, so , “Precision” and “Individualization” are the main development directions of cancer screening. To solve this problem, risk prediction research based on macro and micro factors is an effective strategy to deal with “complex etiological networks” and “strongly heterogeneous” diseases, and is the main starting point for “precision medicine” in the field of major disease prevention and treatment. It is also an important opportunity to take advantage of our country’s population resources and achieve integration with international standards and even lead in the field of precise disease prevention and control.

 

The screening of esophageal squamous cell carcinoma in Chinahas gone through decades of continuous exploration and practice, accumulated a lot of front-line work experience, and established effective working methods and organizational structures. In recent years, with the continuous investment, thinking and innovation of more epidemiological research teams, China has achieved important progress in the precise prevention and treatment of esophageal squamous cell carcinoma. The whole chain of “risk prediction” tools and related standards put forward the practice of accurate screening for esophageal squamous cell carcinoma in China on the international stage. With the advent of the era of medical big data and the era of high-throughput biotechnology, it is foreseeable that the next decade will be a decade of great development in China’s major chronic disease risk prediction and precision prevention and treatment represented by malignant tumors.

 

At present, there are still a series of problems in the early diagnosis and treatment of esophageal squamous cell carcinoma in China, including:

1) It is necessary to further explore the main causes of high risk of esophageal cancer in high-incidence areas. Given that the risk of esophageal cancer in high-incidence areas presents a significantly different gender difference and risk factor framework from non-high-risk populations, based on a large-scale population cohort, joint evaluation of macro-environmental exposure and genetic factors, especially risk factors shared by men and women, is an important direction .

2) Based on the multi-time cross-sectional endoscopic screening and review data of a large-scale prospective cohort, we can accurately estimate various natural history parameters from normal esophageal mucosa to precancerous lesions to the final development of malignant lesions. This is to establish the best screening and The key foundation of the overall control strategy.

3) Based on samples from the early stage of esophageal precancerous lesions and malignant lesions, explore and screen the early warning biomarkers of the onset and progression of esophageal squamous cell carcinoma, and provide new microscopic warning indicators for updating the existing esophageal squamous cell carcinoma related risk prediction model .

4) Make full use of information technology to carry out research on innovation and evaluation of high-standard design endoscopic diagnostic technology, such as establishing an artificial intelligence-based diagnostic auxiliary platform to improve the diagnostic accuracy and standardization of existing endoscopic screening technologies.

5) Carry out a combination of quantitative and qualitative investigations to assess the long-term impact of early diagnosis and treatment on the quality of life of patients, and reveal the status and influencing factors of cancer patients not receiving treatment and not receiving appropriate treatment as detected by screening, Establish post-screening patient management and precise assistance strategies that are in line with the actual situation in China’s rural high-risk areas.

6) Regarding the “precise screening model for esophageal cancer” as a whole as a new health technology, under the framework of “Health Technology Assessment (HTA)”, a comparative study with traditional screening models will be carried out. This model is comprehensively evaluated and applied from multiple dimensions such as adaptability, effectiveness, economy, and ethics, and provides systematic evidence for the establishment of optimal screening strategies in different populations under different resource conditions.

All of the above are the pain points and difficulties in the field of early diagnosis and treatment of esophageal squamous cell carcinoma inChina for many years, and the research experience and results of the high incidence of esophageal adenocarcinoma in the West are of limited value for the prevention and treatment of esophageal cancer in China. Therefore, we advocate that scientists in China’s public health, clinical medicine, basic medicine and all related fields can break disciplinary barriers, use disease as a clue, innovate and collaborate, work hard, and jointly tackle esophageal cancer, a major threat to the health of our nationals. disease.

 

Researches on “precise screening” of esophageal cancer

Researches on “precise screening” of esophageal cancer

(source:internet, reference only)


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