JAMA: Expanded scope of lung cancer screening

Nowadays, lung cancer is one of the important causes of malignant tumor-related deaths.

According to GLOBOCAN 2020 estimates, there are approximately 19.
3 million new cases and 9.
9 million deaths from cancer worldwide.

Lung cancer is the second most common cancer and the main cause of cancer deaths.
It is estimated that there will be approximately 2.
2 million new lung cancer cases and 1.
8 million lung cancer deaths in 2020.

Of the global new cases of lung cancer in 2020, about 37% will come from China.

Among the deaths from lung cancer, Chinese cases accounted for about 39.
8%.

Although WHOWHO has developed rapidly in the treatment of lung cancer in recent years, the overall prognosis has not improved significantly.
The current 5-year overall survival rate is only 16%-18%.

The reason is the lack of effective early diagnosis methods, 70%-80% of lung cancer is diagnosed in the middle and late stages.

The 5-year survival rate for stage I lung cancer is 60%-70%, while the survival rate for stage IV lung cancer is less than 5%.

Therefore, early screening and diagnosis of lung cancer is a key factor to reduce its mortality and prolong survival.

In 2013, the United States Preventive Services Task Force (USPSTF) recommended that American adults aged 55 to 80, current or previous smokers with 30 packs/year, and people who have a history of smoking and quit smoking in the past 15 years, Low-dose computed tomography (LDCT) lung cancer screening is performed annually.

Recently, the USPSTF made two major revisions to the screening recommendations issued in 2013 and published them on JAMA.

The annual screening will be advanced to the 50-year-old smokers, and the smoking intensity will be reduced from 30 packs/year to 20 packs/year.

It is estimated that according to the more inclusive standard of 2021, the number of adults eligible for lung cancer screening has increased from 6.
4 million to 14.
5 million, an increase of 81%.

However, given the limited absorption rate of lung cancer screening and concerns about the gender, race, and ethnicity differences in the 2013 recommendation, can the revised 2021 recommendation be implemented or reduce inequality in screening? , It remains to be seen.

In an editorial published in the Journal of the American Medical Association, Dr.
Louise M.
Henderson, Professor of Radiology at the UNC School of Medicine, and Patricia Rivera, MD, Professor of Medicine at the UNC School of Medicine, stated that expanding the scope of lung cancer screening represents an advancement in medical welfare.
It is pointed out that only expanding the scope of screening cannot reduce racial inequality.
Perhaps it is possible to increase the risk prediction model to identify the defect of high lung cancer risk that does not meet the USPSTF standards.

New evidence supporting the guidelines The 2013 USPSTF’s recommendation statement is based on the results of the National Lung Screening Test (NLST), which found that in 53,454 people aged 55 to 74, currently smoking or quitting smoking (within the past 15 years) ) And among American adults with 30 packs/year, 3 rounds of low-dose CT and chest X-ray examinations are performed every year, and the lung cancer mortality rate is relatively reduced by 20%.

In the past 7 years, randomized clinical trials in Europe have evaluated more evidence on the benefits and harms of lung cancer screening.
Among them, the Dutch-Leuven-Giraffe Screening Onderzoek (NELSON) trial is the largest and the only one outside of NLST.
A randomized trial that can detect differences in mortality.

NELSON reports that of 13,195 men and 2,594 women, aged between 50 and 74, with a history of smoking at least 15 cigarettes per day for 25 years or more, or at least 10 cigarettes per day for at least 30 years , And quit smoking in the past 10 years, 4 rounds of low-dose CT scans in 5.
5 years compared with no screening, the lung cancer mortality rate was relatively reduced by 25%. In addition to randomized trials, the other evidence used to inform this recommendation statement is based on a commissioned analysis of the Cancer Intervention and Surveillance Model Network (CISNET) collaborative modeling study, Rivera and colleagues reported in the Journal of the American Medical Association during the same period For this research.

Using 4 lung cancer simulation models to predict age and sex-specific lung cancer incidence and mortality based on personal smoking history, two screening strategies were evaluated to assess the benefits and harms of lung cancer screening.

One is a strategy based on risk factors, using standards similar to those recommended in 2013.

The second is a risk model-based strategy, which evaluates the eligibility criteria based on a simplified version of 3 multivariate risk prediction models to estimate lung cancer risk.

These models were simplified to include only smoking history, gender, and age, but excluded other risk variables such as race, ethnicity, chronic obstructive pulmonary disease, family history, and personal cancer history.

Using these two strategies, the research team determined a set of screening criteria, which is estimated to be related to reducing lung cancer mortality and increasing the number of years of life obtained.

The strategy based on risk factors identified an effective method, including starting screening at the age of 50 or 55, stopping screening at the age of 80, and a minimum smoking intensity of 20 pack years.

This is an improvement over the analysis performed in 2013, because this new risk-factor-based strategy considers both the avoided lung cancer deaths and the number of years of life gained.

According to a study, this can reduce or eliminate some racial differences.

In addition, future research should explore risks such as family history of lung cancer and genetic susceptibility to develop risk assessment strategies that may identify individuals who have never smoked and still have a high risk of lung cancer, but are currently not eligible for screening.

Dr.
Henderson said that putting screening recommendations into practice will be a substantial challenge.

Primary care providers are critical to the implementation of the screening process, because primary care providers make the first visit to understand the potential risks of lung cancer screening and make screening referrals.

However, the workload of many primary hospitals is already too heavy, and it is difficult to expect them to spend the necessary time for these complicated referrals.

"An important obstacle to the implementation of lung cancer screening is the provider's time.

Many primary care providers do not have enough time for joint decision-making dialogue and risk assessment," Rivera said.

"Although a lung cancer screening risk model that incorporates comorbidities and clinical risk variables may be the best tool for selecting high-risk individuals who are most likely to benefit from screening, this model requires additional input of clinical information, which increases The time spent by medical service providers, the use of this model in clinical practice has not yet been established.

"China’s lung cancer early screening guidelines are in China, January 15 this year, at the Beijing Anti-Cancer Association 2021 Early Cancer Screening Standardization Symposium Last, the "Guidelines for Early Screening of High-incidence Cancers in China" was officially released, giving authoritative guidance on the early screening of ten major tumor types including lung cancer, gastrointestinal cancer, and hepatobiliary cancer.

At the same time, the first "Beijing Anti-Cancer Association Early Cancer Screening Base" landed in Beijing Jingxi Cancer Hospital.

According to the requirements of the "Healthy China Action (2019-2030)", by 2022 and 2030, the 5-year cancer survival rate will increase to 43.
3% and 46.
6%, respectively.

"This is not only to popularize the professional knowledge of health education for the masses, but more importantly, to improve the overall standardization of diagnosis and treatment of oncology medical staff.

" Professor Zhu Jun, secretary of the party committee of Peking University Cancer Hospital and director of the Department of Lymphatic Oncology, pointed out that the tenth of Peking University Cancer Hospital Over the years, the overall 5-year survival rate has reached or exceeded this basic goal.
From a nationwide perspective, there is still a long way to go to reach this goal.

The method of early lung cancer screening, LDCT screening, is currently the most researched and the most recognized is LDCT lung cancer screening.

The I-ELCAP study carried out LDCT examinations on 31,567 high-risk lung cancer patients every year, and found that the detection rate of LDCT lung cancer was more than 4 times that of chest X-ray.
The positive rate of first LDCT detection of lung cancer among people ≥40 years old was 1.
3%.
The positive rate of lung cancer was 0.
3%; the positive rates of lung cancer found in the first LDCT and annual examinations were 2.
7% and 0.
6% in people ≥60 years of age. The results show that more than 80% of lung cancer cases detected by regular LDCT screening each year are stage I, and the expected total 10-year survival rate of lung cancer is 80% (regardless of the clinical stage and treatment); if surgery is performed in time, the expected total 10-year survival rate is as high as 92%.

Small RNAs (microRNAs) protein-based traditional tumor markers such as carcino-embryonic antigen (CEA), serum squamous cell carcinoma antigen (SCC-Ag), etc.
, have low sensitivity to early lung cancer It is less than 10%, and the specificity of distinguishing lung cancer from benign lung disease is low.

miRNAs are a kind of non-coding RNA in organisms, and some microRNAs in tumor patients will have significant changes.

Therefore, the quantitative detection of microRNAs in peripheral blood has become a new focus of early diagnosis of lung cancer.

Circulating tumor cell (CTC) CTC is a malignant tumor cell that exists freely in the circulation, which separates from the primary tumor or metastasis site and enters the blood.

In recent years, new technologies have been developed to identify, isolate and identify these circulating tumor cells from peripheral blood.

Lung cancer autoantibodies The research on lung cancer autoantibodies has also received attention.

With the advancement of detection technology, the application value of autoantibodies is constantly being explored.

Studies have found that in the early stage of tumor onset, the body's immune system can recognize abnormally expressed proteins in tumor cells, trigger an immune response, and produce a large number of antibodies by the immune biological signal amplification system.

Compared with other blood molecular markers, tumor autoantibodies have their unique advantages: ①High early sensitivity: In the early stage of cancer, due to the high specificity and sensitivity of the antigen-antibody reaction, even if there is a large amount in the serum The interference of albumin and other proteins can also be accurately detected at very low concentrations; ②High specificity: there is no or very low content in the serum of healthy people and patients with benign lung disease, while the expression level in tumor patients increases It is easy to differentiate and diagnose early tumor.

The specificity and sensitivity of individual autoantibody molecules are low, which cannot meet the needs of early screening and diagnosis of lung cancer.
However, if several autoantibody molecules are combined for joint screening, the specificity and sensitivity of diagnosis can be greatly improved.
.

Original source: Louise M.
Henderson, PhD1,2; M.
Patricia Rivera, MD1,3; Ethan Basch, MD1.
Broadened Eligibility for Lung Cancer Screening: Challenges and Uncertainty for Implementation and Equity.
JAMA.
2021;325(10): 939-941.
doi:10.
1001/jama.
2020.
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