Lung cancer is currently one of the most common malignant tumors, and its incidence and mortality rate are increasing year by year, posing an increasingly serious risk to human health. There is a significant correlation between the occurrence of lung cancer and heavy smoking, with the risk of the disease in smokers being 10 to 80 times higher than that in nonsmokers. Lung cancer has become the number one cause of malignancy-related deaths in both men and women worldwide. In developed countries such as the United States, the incidence rate has started to decline from its peak stage due to the gradual reduction in cigarette consumption, while in developing countries such as China, the incidence rate of lung cancer has continued to rise as its cigarette consumption rate has gone up.
The global average 5-year survival rate for lung cancer is only 16%, with the average 5-year survival rate for stage IV lung cancer being less than 0.5%, while stage I lung cancer can reach 65%, including 75% for stage IA and 55% for stage IB. Unfortunately, most lung cancers are asymptomatic in the early stage, and when they are detected with symptoms such as cough and sputum blood, they are already in the middle and late stage. Only 10% of patients can be detected in the early stage (stage I), and often in non-tumor related examinations.
Two major principles of lung cancer screening
Early detection of lung cancer through screening has been a hot research topic in recent years. The evaluation of whether a screening method is suitable for lung cancer screening is based on two main principles: beneficial is whether it can detect lung cancer at an early stage, and whether it can ultimately improve patients’ survival and reduce mortality through early detection and timely intervention; harmless is to be painless, non-hazardous, with low false positives, and to avoid unnecessary and invasive examination.
Three types of screening methods commonly used
There are three main types of methods used for screening: X-ray chest X-ray, sputum examination, and low-dose spiral CT.
X-ray chest examination was the main method before the 1990s and helped to detect early peripheral lung cancer. However, a large randomized controlled study in the United States in the 1970s and 1980s confirmed the limited role of chest radiograph screening; digital chest radiography (DR) also failed to improve the detection rate of early peripheral lung cancer and reduce the mortality rate of lung cancer.
Sputum cytology, which is inexpensive, noninvasive, and easy to use, can detect central lung cancer that is missed by X-ray chest radiographs, but is less sensitive.
Spiral CT has been used since the 1990s to detect small peripheral lung cancers with no distant metastases, no or only local infiltration, and a diameter of < 1 cm. 80% to 90% of these tumors can be cured by adequate surgical resection without further radiotherapy or chemotherapy. Large-scale screening programs in Europe, the United States and Japan since the 1990s, using low-dose spiral CT (LDCT) as the main screening method, have shown that the detection rate of malignant lung cancer screening is 1% to 2%, the detection rate of early-stage lung cancer is over 80%, and the 5-year or even 10-year survival rate is over 80%, with an expected 10-year survival rate of 88%. Data from all studies suggest that lung cancer patient survival can be improved by LDCT screening.
Milestone NLST study: LDCT screening in high-risk populations significantly reduces lung cancer-related mortality
The latest results from a 10-year National Cancer Institute (NCI) lung cancer screening trial (NLST), which showed that spiral CT screening of high-risk populations, including smokers or former smokers, reduced lung cancer mortality by about 20 percent, were first published in October 2010 on the NCI website and in 2011 in the New England Journal of Medicine.
The NCI-sponsored study, which cost $2.5 billion and began in 2002, involved more than 53,000 smokers aged 55 to 74 years at 33 sites across the United States, who were randomly assigned to the LDCT and X-ray chest radiograph (XR) groups and screened once a year for a total of three times, followed by five years of follow-up. The incidence of lung cancer was 645 cases/100,000 person-years in the LDCT group and 572 cases/100,000 person-years in the X-ray group (HR=1.13). The lung cancer-related mortality rate in the LDCT group was 247 cases per 100,000 person-years compared with 309 cases per 100,000 person-years in the X-ray group (HR=1.13).
The LDCT group had a lower mortality rate not only for lung cancer but also for all other diseases, and although the reasons for this need to be further explored and demonstrated, the final results showed that the mortality rate for all diseases was approximately 6.9% lower in the LDCT group compared to the XR group (p=0.02).
Approximately 157,000 people die from lung cancer in the United States each year, and based on this result 27,000 of them may be saved by LDCT screening for lung cancer.
NCI’s ALBERT claims that screening 320 cases is needed to reduce lung cancer deaths by 1, a much lower figure than breast cancer screening, which requires screening 414-519 women for every 1 reduction in deaths.
This NCI screening program only targets high-risk individuals who have a history of 30 packs/year of smoking, meaning a cumulative smoking history of 1 pack/day for 30 years, or 2 packs/day for 15 years, and so on.
Given the obvious benefits of screening, it is also important to note that in the NLST and all other large international screening studies, there are no data to suggest that these once-a-year (mostly 3-year) LDCT screenings cause significant harm to participants.
Technically conventional CT examinations are not appropriate as a routine screening follow-up method due to the high X-ray radiation dose, with a single chest CT examination X-ray radiation dose equivalent to 8-9 mSv, 60-100 times the X-ray dose of a plain chest radiograph (0.08-0.12 mSv). Multilayer spiral CT scanning has the advantage of faster scanning speed and lower dose, by reducing the tube current and tube voltage in that the detection rate is not affected by thin-layer reconstruction. LDCT is now becoming technically mature, and the radiation dose of the scan is about 2.0 mSV, which is significantly lower than conventional CT, and is the most effective means of lung cancer screening.
Another negative factor associated with screening is the problem of false positives, which may add unnecessary tests for some people who do not have the disease, but can be controlled by experienced and qualified physicians who have a strict grasp of diagnostic criteria and consultation procedures to minimize the harm as much as possible.
Enhanced LDCT screening for high-risk groups
In the United States, in order to reduce the risk of cancer to public health, the U.S. government has approved screening for breast cancer, colorectal cancer, and prostate cancer, but because these cancers lack a relatively clear high-risk population limit, the screening is not efficient. In order to promote lung cancer prevention and control, we urgently need to increase tobacco control and reduce environmental pollution, and the most effective measure is regular medical checkups for high-risk groups: long-term smoking, smoking index of 400 years or more (the number of years of smoking multiplied by the number of cigarettes smoked per day), secondhand smoke for more than 20 years, long-term work in a closed environment, long-term work in an environment with many dust particles, and family history of lung cancer. People with a family history of lung cancer need to have a low-dose CT screening scan once a year after the age of 50.
In order to better prevent and treat lung cancer, reduce mortality and improve survival of patients with lung cancer, for heavy smokers, outpatient visits for low-dose fee CT scan screening are recommended, and people with negative results can participate in the second year of screening; for further treatment of positive results, after objective assessment of risk by experienced radiologists, further treatment measures can be taken including: follow-up review; post-anti-inflammatory review; puncture biopsy thoracoscopic or minimally invasive surgical biopsy.