Despite the benefit to lung cancer mortality rates associated with low-dose CT (LDCT) screening as demonstrated by the National Lung Screening Trial (NLST), enthusiasm for LDCT should be kept in context. That's because much uncertainty remains about the potential harms of screening and the generalizability of results, according to a review of relevant literature published online May 20 in the Journal of the American Medical Association.

“The value of LDCT screening is likely determined primarily by the risk of lung cancer versus competing causes of death,” wrote Peter B. Bach, MD, of the Memorial Sloan-Kettering Cancer Center in New York City, and colleagues.

The systematic review of evidence looked at 591 citations, of which eight randomized trials and 13 cohort studies met inclusion criteria. Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality. The NLST, with more than 50,000 participants, was the most informative and showed screening resulted in a 20 percent lower relative risk for lung cancer death. However, no such benefit was seen in the other two, smaller studies.

“In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20 percent of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1 percent had lung cancer,” wrote the authors. “There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions.”

Bach and colleagues outlined some of the potential harms of LDCT screening, including:

• Detection of benign abnormalities;
• Complications from diagnostic procedures;
• Overdiagnosis of cancers that would not affect the patient during his or her lifetime if left untreated;
• Radiation exposure; and
• Reduced quality of life stemming from anxiety or costs.

Studies measuring LDCT screening’s effect on a patient’s smoking habits produced little evidence, though Bach et al noted that speculation could lead to two different conclusions. Negative findings could justify a continuation of smoking, or screening could be used to support intervention in a patient’s smoking habits.

“Even a small negative effect of screening on smoking behavior (either lower quit rates or higher recidivism) could easily offset the potential gains in a population. Smoking cessation should be considered a valuable component of any screening program,” wrote the authors.

The report was used as the basis for a pair of clinical practice guidelines from the American College of Chest Physicians and the American Society of Clinical Oncology. The first recommendation is that annual LDCT screening should be offered to smokers and former smokers ages 55 to 74 years who have smoked for 30 pack-years or more and either continue to smoke or have quit within the past 15 years. These screenings should only occur in a setting that can deliver the level of care provided to NLST participants.

“The association between the setting of LDCT screening and outcome has not been tested, but variability in rates of false-positive LDCT scans, further imaging, and procedures suggests these may be important,” wrote the authors.

The second recommendation is that individuals outside of the 55 to 74 year age range or those who have less of a smoking history should not undergo CT screening. Additionally, those with severe comorbidities that would preclude curative treatment or limit life expectancy should not receive LDCT screening.

“The unexplained heterogeneous rates of nodule detection, additional imaging, and invasive procedures that occurred within the structured settings of the controlled trials of LDCT raise concerns about how easily LCDT can be more broadly implemented,” concluded the authors. “Given all of these issues, performing an LDCT scan outside of a structured organized process appears to be beyond the current evidence base for LDCT lung cancer screening.”

For more on lung cancer screening, read “Inside a Comprehensive Lung Cancer Screening Program,” a guest column published in the May issue of Health Imaging.