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text/zhuang shili and phoenix.com "cc intelligence bureau" special expert

key points:

1. on august 28, the famous magician liu qian revealed that he had lung adenocarcinoma. he had been observing his lung nodules since he discovered them 3 or 4 years ago. it was not until february this year that he removed them because they had worsened. liu qian provided an excellent model for how to deal with and reexamine lung nodules after discovering them.

2. lung nodules do not reflect whether they are benign or malignant. the size, shape and density of the nodules are crucial to determine the nature and development of the nodules. a large number of lung nodules may be inflammation, lesions of previous infections, tuberculosis, hamartomas and lipomas, which have nothing to do with malignancy. in pathological staging, a nodule has four stages from precancerous lesions to adenocarcinoma: aah, ais, mia, and ia. the latter two require surgery and other treatments as soon as possible.

3. the incidence and diagnosis and treatment levels of lung cancer vary in different countries or regions, and different guidelines have different treatment standards for lung nodules, but the basic principle is to weigh the pros and cons. high-risk nodules should be intervened as early as possible, and non-high-risk nodules should be followed up and monitored to avoid overtreatment. low-dose spiral ct screening of people at high risk of lung cancer can detect lung cancer early, improve prognosis, and reduce lung cancer mortality.

4. for chinese people, more ct screening can detect more lung cancers, but it may also lead to more treatments. whether these treatments can reduce the mortality rate of the entire population still needs more research. for all cancer screenings, the current trend is to recommend reducing routine screening. now, some screenings may not bring real benefits and may even cause potential harm.

on august 28, the famous magician liu qian personally confirmed that he was suffering from lung adenocarcinoma!

liu qian revealed in an interview with taiwanese media that he discovered a nodule in the middle back part of his lung during a health check-up 3 or 4 years ago. he has been having regular follow-up check-ups since then. he had a routine ct scan before performing at this year's spring festival gala and highly suspected that the nodule had become a disease.

in mid-february this year, liu qian was diagnosed with stage 0 lung adenocarcinoma after pathological analysis and underwent surgery.

lung cancer is generally divided into two major types, small cell lung cancer (sclc) and non-small cell lung cancer (nsclc).lung adenocarcinoma is a type of lung cancer, belonging to non-small cell lung cancer. among lung cancer patients, lung adenocarcinoma accounts for 60% and lung squamous cell carcinoma accounts for 30%, which is the most common pathological type. unlike squamous cell lung cancer, lung adenocarcinoma is more likely to occur in young women, those with a history of smoking, and asians. it is often located in the periphery of the lungs, and the tumor expands slowly (doubling time is about 120 days). there are no signs in the early stage, and it is usually diagnosed in the late stage.

non-small cell lung cancer is further divided into adenocarcinoma, squamous cell carcinoma and poorly differentiated large cell carcinoma.

there is increasing evidence that driver genes play a pivotal role in the development of lung adenocarcinoma. the most common driver gene mutations are egfr (70%), eml4-alk (10.6%), her2 (8.5%), and kras (6.3%).

other studies have shown that patients whose immediate family members have lung adenocarcinoma are more likely to develop lung adenocarcinoma.liu qian's uncle died of lung cancer, which shows that there is evidence that lung cancer is hereditary in liu qian's family.

if lung adenocarcinoma can be detected in the early stages and treated promptly with surgery, the five-year survival rate and cure rate can reach over 90%. as long as the cancer cells have not metastasized to the lymph nodes or further afield, they can be completely removed with surgery, and the cure rate can even reach 100%. however, regular follow-up examinations are also required after treatment to prevent cancer recurrence.

at present, liu qian's lung adenocarcinoma is in the early stage and the cure rate should be very high.

liu qian's lung adenocarcinoma was discovered and removed in time due to a lung nodule he found three years ago. he had been observing his lung nodules for at least three years, until february this year, when he found that they had worsened and had them removed.

liu qian provided an excellent model for how to deal with and review the problem of lung nodules after they are discovered. due to the increase in ct accuracy and many necessary or unnecessary lung ct examinations in the past few years, many people have been found to have lung nodules. according to the 2016 cancer statistics released by the national cancer center in 2023, lung cancer morbidity and mortality ranked first. in 2016, there were approximately 828,000 new cases of lung cancer in china and approximately 657,000 deaths from lung cancer.when a lung nodule is found during a physical examination, the most worrying question is whether the nodule is malignant? should surgery be performed or continued observation be performed? how often should a follow-up examination be performed? could it be lung cancer?

what are lung nodules?

before talking about lung nodules, let’s first talk about some basic knowledge about the lungs.

humans have two lungs, one on the left and one on the right. but in fact, the two are not symmetrical. the right lung has three lobes, while the left lung has two lobes. this is related to the position of the heart.

the heart is located on the left side and occupies a certain amount of space. therefore, not only humans, but also some mammals such as cats and dogs have more lobes in the right lung than the left side.

however, the lung is an internal organ, and it is difficult for doctors to directly observe what these lesions look like and where they are located in the lungs. therefore, doctors use imaging methods to examine these problems.in the imaging examination of the lungs, a commonly used method is to take a ct scan. you can think of ct as a combination of a bunch of x-ray films. the machine goes around you and you can get a lot of tomography images.

andthe so-called pulmonary nodule is a round-shaped lung mass in imaging.that's all, and it doesn't reflect whether it is good or evil.

how to screen for lung nodules? should we use ct or pet-ct? is the radiation high?

according to the chinese guidelines for lung cancer screening, early diagnosis and treatment released in 2021, the most important screening method for lung cancer is ct. domestic and foreign evidence shows that low-dose spiral ct screening of people at high risk of lung cancer can detect lung cancer early, improve prognosis, and reduce lung cancer mortality.

here are a few points to note in actual application.

the first is low-dose ct.as a screening method, it is aimed at ordinary people rather than patients, so more consideration should be given to the risks brought by the examination itself.the main risk of ct is radiation.although the radiation from a single exposure is not large for a specific individual,however, the possible radiation risks still need to be considered for the group.

each of us receives about 2~3msv/year of natural background radiation, which comes from cosmic rays, radiation from various natural materials, etc. for example, a round-trip flight from new york to paris receives about 0.12msv of radiation, which is about the level of a chest x-ray. the radiation dose of an ordinary chest ct scan is 5~6msv, and the radiation dose of a low-dose ct scan is about one-sixth of that of an ordinary ct scan, so it is more suitable for screening lung diseases.

the second concept to be discussed is layer thickness.you can see that the ct scans in hospitals have xx rows. rows refer to the number of detector arrays. the more rows there are, the clearer the image is. another factor is layer thickness. layers refer to the number of images produced by a ct scan, and layer thickness refers to the thickness of each layer. the traditional one is generally 5mm. now many hospitals have 2mm, 1mm or even thinner thin-section ct (thin-section ct, tsct, note that low dose and thin layer are two independent concepts).

for the screening of lung nodules, it is usually recommended to select an image reconstruction layer thickness of 1mm. the lower the layer thickness, the clearer the morphology of the nodule can be seen, and the more accurate the clinical advice that the doctor can give.

the third is that pet-ct screening is not recommended.the radiation emitted by pet-ct is twice that of ordinary ct (from the radioactive glucose in the pet part), and it is expensive, costing 8,000 to 10,000 yuan per session. taking into account the problems of false positives and false negatives, pet-ct is not suitable for screening of lung nodules, unless it is deemed necessary after low-dose ct screening.

about half of the people who participate in physical examinations can be diagnosed with lung nodules, and about 5% can be diagnosed with lung cancer!

according to the american thoracic society (ats),among people who have undergone lung ct and x-ray, up to half will be found to have lung nodules, but most lung nodules are benign, and less than 5% of lung nodules will cause cancer.

many people are most concerned about the size of the nodule, but in fact, there are two other very important factors: the shape and density of the nodule, which are crucial to judging the nature and development of the nodule. in terms of pathological staging, a nodule may have several stages from precancerous lesions to adenocarcinoma:

-aah (atypical adenomatous hyperplasia);

-ais (adenocarcinoma in situ);

-mia (minimally invasive adenocarcinoma);

-ia (invasive adenocarcinoma).

please note that the above are only lung nodules with malignant tendencies. there are also a large number of lung nodules that may be caused by inflammation, lesions of previous infection, tuberculosis, hamartomas, lipomas, etc., which have nothing to do with malignancy.

generally speaking, aah and ais are considered precancerous lesions, not cancer.(although ais contains the word "cancer", it is almost impossible to metastasize and is not considered cancer in the strict sense);

mia and ia are cancers, the difference is the depth of invasion(mia refers to an infiltration depth of less than or equal to 5 mm, and ia refers to an infiltration depth of greater than 5 mm). for patients who have developed ia, they are further divided into stages i to iv based on tumor size (t), lymph node metastasis (n), and distant metastasis (m).

therefore, you must be careful with these two types of nodules and undergo surgery or other treatments as soon as possible.

in addition, according to whether the pulmonary nodules cover the lung parenchyma on imaging, they can also be divided into

- solid nodule;

-part-solid nodule;

-non-solid nodules (pure ground-glass nodules, pure ggn)

[the latter two are also collectively referred to as subsolid nodules.]

will lung nodules grow larger? does a large lung nodule mean lung cancer?

therefore, it is particularly important to accurately evaluate these nodules, and the key to the evaluation isin addition to size, the solidity (or density) of the nodule may be more important.

let’s take ground glass nodules as an example.we divide ground glass nodules into two parts: solid ground glass nodules and pure ground glass nodules.

let’s first talk about the relatively more dangerous part-solid ground glass nodules (part-solid ggo)

in fact, many partially solid ground glass nodules are stable.according to some clinical studies, after long-term follow-up, 58% of partially solid ground glass nodules did not change, 24% increased in volume, and 18% increased in solid components. the situation of pure ground glass nodules was better. during long-term follow-up, 83% of pure ground glass nodules did not change, 9% increased in volume, and 8% increased in solid components.

this picture shows the results of another study, which is a synthesis of five different clinical studies. for example, in the study by kakinuma and other researchers, based on a 6-year follow-up study of 439 patients, the pure ground glass nodules of these patients were all less than 5 mm, and almost 90% of the nodules did not change.

so everyone must remember one thing,not only the size of the nodule is important, the density of the nodule is also very important.this is also the reason why some patients often ask me with their reports, or even just a sentence on wechat like "hello, doctor, i found a 5mm nodule in my right lung during this physical examination. what should i do?" these questions cannot be answered.

for a responsible doctor, i think he must see the images with his own eyes in order to give the patient an accurate assessment.

how to follow up after discovering lung nodules?

different guidelines have different standards for the treatment of lung nodules, and there are even differences between china's own expert consensus and guidelines.

because the incidence and diagnosis and treatment levels of lung cancer vary from country to country,the basic principle is to weigh the pros and cons. high-risk nodules should be intervened as early as possible, and non-high-risk nodules should be followed up and monitored to avoid overtreatment.

overall, based on different guidelines,nodules smaller than 6 mm do not require routine follow-up，for nodules larger than or equal to 6 mm, the specific diameter, whether they are solid or subsolid, and the presence or absence of risk factors should be considered.

subpleural nodules

▎yellow arrows indicate solid lung nodules

▎triangular perifissure lymph nodes can be diagnosed as benign lymph nodes

▎ ground glass nodules

the following pictures of solid nodules and subsolid nodules are a combination of the opinions of four major societies: the american college of chest physicians (chest), the fleischner society (an authoritative international chest radiology society), lung-rads (lung imaging reporting and data system, a classification guide developed by the american college of radiology), and the british thoracic society (bts).

the picture below is the lung-rads guidelines (chinese translation published by nejm), which is more intuitive.

can lung cancer screening really reduce mortality? why does the united states not recommend lung cancer screening among non-smokers?

the most important purpose of any screening we are talking about is to reduce the mortality rate (note, not the case fatality rate).cancer mortality refers to the proportion of cancer-related deaths to the total population over a certain period of time, usually calculated on a per 100,000 population basis.

if a screening test is implemented on a large scale in a population, but the results show that it is not effective in reducing the mortality rate, or even increases the mortality rate, then the screening test is ineffective.for example, the main reason why the united states no longer recommends psa (prostate-specific antigen) screening for all men is that psa screening may lead to a large amount of overdiagnosis and overtreatment of prostate cancer.this means that some men may be treated but their prostate cancer may not pose a significant threat to their lifespan.

back to lung cancer, in the united states and many european countries, lung cancer screening is mainly carried out among high-risk groups, that is, smokers.the results of two large randomized controlled trials, nlst in the united states and nelson in europe, showed that lung cancer screening for high-risk groups (smokers aged 55-74 years) is effective and can reduce lung cancer mortality by approximately 20%.

according to clinical research data from the united states,the u.s. preventive services task force (uspstf) does not recommend lung cancer screening for people who have never smoked.this is because for this group, the harms of screening outweigh the benefits of screening (early detection of lung cancer).

▎this image shows the various visual manifestations of lung nodules

why are there more non-smokers among lung cancer patients in east asia? why can't early detection reduce the mortality rate?

however, the situation in east asian populations is a little different.

10-15% of lung cancer patients in the united states have never smoked, which means that most lung cancer patients in the united states are smokers.but among lung cancer patients in east asia, the proportion of never-smokers is much higher.this difference may be related to cancer-driving genes, as well as secondhand smoke environments, kitchen fumes, etc. for example, among lung cancer patients in east asia who never smoke, 60% to 80% have egfr (epidermal growth factor) mutations, while the proportion of egfr mutations is much lower among lung cancer patients in europe and the united states.

in japan, 31% of male patients and 80% of female lung cancer patients are never smokers. the statistics in china and south korea are somewhat similar to those in japan. in both countries, about 40% of lung cancer patients are never smokers, especially among female lung cancer patients.therefore, whether it is necessary to conduct lung cancer screening for people who have never smoked has become a difficult problem facing east asian countries.

first of all, if this group of people is not screened, many lung cancer patients may be missed.

a study by the national cancer center of japan showed that although people who smoke more than 30 packs a year have a higher risk of lung cancer than non-smokers and those who smoke less than 30 packs a year, about 70% of lung cancer patients will be missed if lung cancer screening (ldct) is not performed on the latter two.

however, screening more lung cancer patients does not mean that the mortality rate can be reduced.

a study by the shanghai cdc showed that after the introduction of ldct screening, the incidence of lung cancer in women in shanghai increased significantly from 2011 to 2015, but the mortality rate of lung cancer in women did not decrease during the same period.

therefore,for chinese people (especially chinese women), more ct screening can detect more lung cancers, but it may also lead to more treatments. whether these treatments can reduce the mortality rate of the entire population still requires more research.

some people may ask, why can't early detection reduce the mortality rate?

for almost all cancers, the earlier the stage, the better the treatment effect and the higher the 5-year survival rate. this is true, but there is another concept here, which is the lead-time bias of cancer screening.

it may be difficult to understand just by looking at the name. a study in ann intern med gave an example to explain:

a man with a persistent cough and weight loss was diagnosed with lung cancer at age 67 and died of cancer at age 70. the five-year survival rate for a group of patients like this man is zero.

if this man had been screened earlier and his lung cancer was found earlier (say, when he was 60) and removed, but he still died at age 70, then his life span would not have been extended, but a group of patients like this man would have a 5-year survival rate of 100%.

there is indeed a big difference in the five-year survival rates before and after, but this man's life was not extended by a day due to early screening. perhaps earlier medical intervention may have reduced his quality of life.

there is another somewhat similar concept in cancer screening called length bias, which refers to the fact that screening is more likely to detect slower-growing, less aggressive cancers (which can be simply understood as indolent cancers), which exist in the body longer before symptoms appear than faster-growing cancers.

if overdiagnosis occurs, screening may detect indolent cancers that may never cause harm or require treatment during a patient’s lifetime, without any way to assess whether treatment resulting from screening actually saves lives.studies have shown that 19% of breast cancers detected by screening and 20% to 50% of prostate cancers detected by screening are overdiagnosed.

the national cancer institute states that for all cancer screenings, the current trend is toward recommending less routine screening. these recommendations are based on an evolving understanding (albeit counterintuitive) thatthat is, more screening does not necessarily mean fewer cancer deaths, and some screening tests may actually do more harm than good.

who is at high risk of lung cancer?the chinese lung cancer ct screening guidelines recommend screening for three high-risk groups

so, back to lung cancer screening in china.

we have a few points that are clear:

-the high-risk group for lung cancer is smokers over 50 years old;

- among chinese lung cancer patients, there are a large number of non-smokers;

-more ldct screening can detect more lung cancers, increasing the incidence rate, but not necessarily reducing the mortality rate.the psychological burden, radiation harm, and overtreatment caused by excessive screening need to be evaluated.

due to the improvement of ct accuracy and the assistance of ai, many normal people who have undergone chest ct scans during routine physical examinations will be found to have lung nodules.the most direct impact of this discovery is anxiety.many people therefore underwent frequent ct scans, while some underwent surgical resection.

based on the current research results,the chinese lung cancer low-dose ct screening guidelines recommend a screening age range of 50 to 80 years old.the main ones are:

- people who have smoked more than 20 packs per year or have been exposed to passive smoking for more than 20 years, or those who have quit smoking within five years;

- history of long-term exposure to specific occupational carcinogens;

- first- or second-degree relatives have lung cancer and smoke more than 15 packs per year or have been exposed to passive smoking for more than 15 years.

if you are not one of the above people, you should be cautious when choosing to do a chest ct during a physical examination. some screenings may not bring real benefits and may even cause potential harm. in the future, perhaps future research will bring new discoveries and adjust screening strategies, but we are not living in the future, but in the present, so please refer to the latest guidelines.

finally, although many of the lung cancer patients detected by screening in east asia are never smokers,however, their prognosis is still significantly better than that of smokers, so quitting smoking is still strongly recommended as an important means of preventing lung cancer (and many other cancers).

i hope this article helps you and your family.