Worldwide lung cancer has the highest rate of mortality and is the leading cause of cancer deaths. The incidence of lung cancer is approximately equal to its mortality. There are approximately 1.8 million new cases of lung cancer every year globally and over 1.6 million deaths secondary to this. The survival rates for lung cancer are abysmal, in the united states the overall 5-year survival is as low as 18% which is in sharp contrast to the high rates of survival for breast, colon, and prostate cancer at 90, 65 and almost 100% respectively.
These low rates of survival link directly with most lung cancers only getting diagnosed when the disease is in advanced stages. Before screening interventions, lung cancers in early stages were found mostly as a coincidental finding. Due to the late presentation of these patients, survival beyond a few years was not possible. Due to these problems, there was a global push for screening modalities for lung cancer to ensure the identification of malignancy occurred earlier in the disease process. The average 5-year survival in the united states of patients with lung cancer is 17.7%; however, this number drastically changes if we account for the stage of the disease at the time of diagnosis.In patients with localized disease, the survival rates are as high as 55.2%. However, only 16% of patients get diagnosed at this early stage of their disease. This difference in survival rates further highlights the absolute need for a relaible screening tool for patients at risk for lung cancer.
Screening methodologies for various cancers have helped in early detection of and better survival of patients. For lung cancers, there have been debates since the 1960s about appropriate screening methods and the risk-benefit ratio. For screening to be effective, implementation in the right population with the benefits outweighing the possible harms is the key. Therefore, it should be limited to people at high risk for the disease as there is a real possibility of harm associated with overdiagnosis including unnecessary tests, invasive procedures, and psychological distress.
There were several studies done in the 1960s and 70s using chest X-rays as screening tools. These studies, though limited by the lack of a control group, showed no mortality benefit for chest x-ray screening. The 2010 prostate lung colorectal and ovarian cancer screening trial (PLCO) definitively proved the lack of screening benefit with x-rays for lung cancer. In 2011 the national lung screening trial was published and was the most significant trial conducted globally to determine the benefit of screening for lung cancer. The trial found that with low dose CT scans; detection of more stage-1 cancers took place. The results from this study showed a mortality benefit in a subset of the general population. It showed a decrease in lung cancer deaths in heavy smokers or people with a history of heavy smoking. The low dose CT scan (LDCT), when used for screening, led to approximately 3 fewer deaths per 1000. Overall, the use of LDCT when compared to chest x-ray reduced lung cancer-related deaths by 20%.
The United States Preventative Services Task Force (USPSTF) based their recommendations on the findings from the NLST. In 2013 they recommended lung cancer screening with low dose computed tomography in adults within the age range of 55-80 years with a history of 30-pack-years of smoking who are active smokers or quit within the last 15 years.
Globally, tobacco use remains the most significant cause of lung cancers, and even with the current screening technologies, primary prevention is far more effective in decreasing the occurrence and mortality associated with lung cancer. Smoking cessation should be emphasized in every clinical encounter and recognized as the most effective way to counteract lung cancer incidence. Tobacco use directly relates to over 80% of lung cancer deaths.
The biggest limitation of any screening test is its sensitivity and specificity. For LDCT there is a very real concern for over diagnosis leading to inflated costs and emotional distress. Across all the trials conducted for the LDCT approximately 20% of individuals screened had a positive result, however, only 1% had lung cancer. Everyone who screened positive required follow-up tests including further imaging and in some rare instances invasive testing for biopsies and surgical interventions for benign lesions.
Radiation exposure is another very serious concern related to regular screening. The risk of radiation from medical tests is low however it is a theoretical possibility. The ionizing radiation can cause DNA damage leading to double-stranded breaks which if not repaired correctly, will lead to mutations and possible cancers. Therefore, it is important to select the right population and to have a detailed conversation with patients about the risks and benefits.
As with all screening modalities, LDCT requires open and honest communication between patients and clinicians and it is imperative that the physician and patient engage in shared decision making. Shared decision making allows for providers to give patients all the relevant information regarding a screening test, including the possibility of false-positive results, the options for further diagnostic testing and the risks associated with undertaking each test. Recommendations are also that when discussing screening options for lung cancer, tobacco cessation must be part of the discussion, and the harms of tobacco use explained in detail and not restricted just to the association with lung cancer.
USPSTF recommends annual screening with the LDCT. Studies have shown that using decision aids which can be written, video or internet-based information about outcomes and options, help patients understand the recommendations and improve adherence. A Cochrane collaboration showed that when given educational aids, patients had an increased engagement in decision-making, better knowledge and a better understanding of risks and benefits.
The National Comprehensive Cancer Network (NCCN) recommends screening for high-risk populations. They identify two particular subsets of the populations at high risk: first, those who meet the criteria set forth by the NLST, which is adults between 55-80 years of age with a 30-pack-year smoking history who are active smokers or quit within the past 15 years. The second population they identify are adults aged >50 years with over 20 pack year smoking history and an additional risk factor for lung cancer. These additional risk factors include environmental, occupational or residential exposure to carcinogens, family history of lung cancer, COPD or pulmonary fibrosis.
The NLST trial only conducted screening for 3 years, however clinically there is an increased risk of cancer with increased age. Therefore, it is recommended to continue screening annually unless the patient has a life-limiting condition. The NELSON trial confirmed this finding. They found during this trial that an annual low- dose CT decreased lung cancer deaths in men by 26% and in women by 61% with an overall decrease by 44%.
It is essential to have a detailed discussion tailored to each patient detailing their risks and explaining the pros and cons of screening. In the future, the need will exist to develop better predictive tools to help localize at-risk patients and focus on those populations for screening. Ultimately, primary prevention has the most significant impact on lung cancer associated mortality, however secondary prevention is also essential. Studies have shown decreased deaths with screening, and overall the benefits of screening outweigh the risks if the correct population is selected. Clinicians must talk about smoking cessation along with screening and patients with positive LDCT must have close follow-ups.
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