Lung cancer screening

Lung cancer screening refers to strategies used to identify early lung cancers before they cause symptoms, at a point where they are more likely to be curable. Screening refers to the use of medical tests to detect disease in asymptomatic people. Screening studies have only been done in high risk populations, such as smokers and workers with occupational exposure to certain substances.

Practice guidelines

Clinical practice guidelines previously issued by the American College of Chest Physicians in 2007 recommended against routine screening for lung cancer because of a lack of evidence that such screening was effective.^[1] The newest ACCP guidelines take into account findings from the National Lung Screening Trial and state: "For smokers and former smokers who are age 55 to 74 and who have smoked for 30 pack-years or more and either continue to smoke or have quit within the past 15 years, we suggest that annual screening with low-dose CT (LDCT) should be offered over both annual screening with CXR or no screening, but only in settings that can deliver the comprehensive care provided to National Lung Screening Trial participants (Grade 2B)".^[2]

In 2004, a clinical practice guideline by the US Preventive Services Task Force (USPSTF) gave a grade I recommendation indicating that "the evidence is insufficient to recommend for or against screening asymptomatic persons for lung cancer".^[3][4] In July 2013, the USPSTF released a draft version of their updated recommendation that LDCT be used for screening for high risk patients based on age and smoking history. (Grade B recommendation) USPSTF Lung Draft

Following the National Cancer Institute's National Lung Screening Trial, guidelines were released initially in 2012 by the National Comprehensive Cancer Network, an alliance of twenty one cancer centers in the United States. Their consensus guidelines, which are regularly updated, support screening as a process, not a single test, and discuss risks and benefits of screening in high risk individuals within a comprehensive multidisciplinary program. Screening is only recommended for individuals defined as high risk meeting specific criteria. More details can be found in their Patient Guidelines. While lung cancer screening programs have been supported by the NCCN, International Association for the Study of Lung Cancer (IASLC), American Cancer Society, The American Society of Clinical Oncology (ASCO), and other organizations, the screening CT is not typically covered by most insurers at the present time.

Studies of efficacy

Efficacy of screening is primarily assessed by how significantly a screening test decreases mortality. The effect can be measured by calculating either lung cancer-specific mortality or all-cause mortality, which may provide a more accurate risk assessment by factoring in risks incurred with intervention. Studies tend to demonstrate an increased survival time in patients who undergo frequent screening, but this can be misleading measure of screening efficacy because of lead time bias. Simply detecting a tumor at an earlier stage may not necessarily lead to improved survival. For example, plain chest X-ray screening resulted in increased time from diagnosis of cancer until death and those cancers being detected by screening tended to be earlier stages. However, these patients continued to die at the same rate as those who are not screened.

Chest X-Ray

Lung cancer screening programs that utilize plain chest x-rays (CXR) and sputum analysis programs have generally not been found effective in reducing mortality from lung cancer.^[5] The Mayo Lung Project, followed over 9000 male smokers over 45 years of age who smoked 1+ packs/day from 1971 to 1986 and compared intensive CXR and sputum screening every three times per year compared to less frequent annual screening. The results showed that more frequent screening resulted in higher resectability rate (more early-stage detection), but made no difference in mortality from lung cancer. CXR screening were found to detect 6 times as many new cancers as sputum tests.^[6]

CT scans

A computed tomography (CT) scan can uncover tumors not yet visible on an X-ray. This led to CT scanning being actively evaluated as a screening tool for lung cancer in high-risk patients.

The International Early Lung Cancer Action Project (I-ELCAP) published the results of CT screening on over 31,000 high-risk patients in late 2006 in the New England Journal of Medicine.^[7] In this study, 85% of the 484 detected lung cancers were stage I and thus highly treatable. Historically, such stage I patients would have an expected 10-year survival of 88%. Critics of the I-ELCAP study point out that there was no randomization of patients (all received CT scans and there was no comparison group receiving only chest x-rays) and the patients were not actually followed out to 10 years post detection (the median followup was 40 months). Regardless of these shortcomings, it is generally recognized that the prognosis of lung cancer decreases dramatically when the disease is in late stage,^[8][9] and that CT screening for lung cancer allows detection of lung cancer during its earliest, most curable stage. CT screening for lung cancer has already been extensively compared to chest x-ray screening in Japan. Among over 6,800 subjects screened in Japan, 67% to 73% of CT-detected lung cancers were missed by chest x-ray, the same test used in the comparison group of some randomized controlled trials of lung cancer screening.^[10][11][12]

In contrast, a March 2007 study in the Journal of the American Medical Association (JAMA) found no mortality benefit from CT-based lung cancer screening.^[13] 3,200 current or former smokers were screened for 4 years and offered 3 or 4 CT scans. Lung cancer diagnoses were 3 times as high, and surgeries were 10 times as high, as predicted by a model, but there were no significant differences between observed and expected numbers of advanced cancers or deaths.^[14] Additional controversy arose after a 2008 New York Times reported that the 2006, pro-CT scan study in the New England Journal of Medicine had been funded indirectly by the parent company of the Liggett Group, a tobacco company.^[15]

The National Cancer Institute funded a $300m study, the National Lung Screening Trial (NLST), which began in 2002, to compare the effectiveness of CT scan screening versus X-ray screening.^[16][17] This study, too, raised concern in the media over potential conflicts of interest related to the tobacco company, although this time on the contra-CT scan side: on October 8, 2007, the Wall Street Journal reported that at least two lead investigators of the study had conflicts of interest arising from their serving as paid, expert defense witnesses for the tobacco industry – one of them had given testimony asserting that promoting CT screening was "reckless or irresponsible", and another had provided an expert report warning that CT screening "may do more harm than good."^[18]

The National Cancer Institute' National Lung Screening Trial involved over 53,000 former and current heavy smokers aged 55 to 74, who either received three CT scans or three X-rays annually.^[16] Deaths in either group were then logged for up to five years.^[16] As of October 2010, 354 people in the CT scan group had died from lung cancer, versus 442 people in the X-ray group; in other words, deaths in the CT scan group of patients were 20.3% lower than in the X-ray group.^[16] The study's review board concluded that this difference was statistically significant and recommended terminating the study.^[16] The director of the National Cancer Institute's director, Harold Varmus, said that early analysis results appeared to indicate that CT scans detected more lung cancers, at an earlier and more treatable stage, and that CT scans could therefore somewhat reduce the number of deaths in patients at high risk of lung cancer.^[16] Researchers associated with the study cautioned that the preliminary results did not constitute sufficient grounds to make the general public undergo CT scans and that further research and analysis of the data was necessary.^[16] The benefits of screening would have to be balanced against the risks associated with false positives – suspicious CT scan findings that in the end prove not to be cancer-related (although if the randomized data holds this demonstrates the benefits of screening outweigh the negatives of false positives on mortality) – and there is as yet no data showing how CT scan screening would benefit other sections of the population, such as people who had only smoked for shorter periods of time.^[16]

Other methods

Studies have explored other means of testing including breath tests and blood test to detect for lung cancer but none thus far have been clinically validated to be useful to be applied in screening.^[19][20]

Risks of Screening

There are a variety of risks that are inherent to lung cancer screening which must be weighed carefully against the known benefits. Any risk assessment must also factor in risks associated with subsequent work-up and management of suspicious results. Risks include radiation exposure, false positive findings, false reassurance from false negative findings, overdiagnosis, short term anxiety/distress, and increased rate of incidental findings.^[21] Radiation exposure from repeated screening studies could actually induce cancer formation in a small percentage of screened subjects, so this risk should be mitigated by a (relatively) high prevalence of lung cancer in the population being screened.

References