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Small pulmonary nodules classified as "negative" by CT imaging had a 1-3% chance of progressing to lung cancer, supporting recommendations that discourage increased surveillance for such micronodules, according to data from the National Lung Screening Trial (NLST).

Among 409 patients with a micronodule (<4 mm) and a subsequent lung cancer diagnosis, the cancer evolved from the micronodule in 13 cases, which accounted for 1.2% of all lung cancer diagnoses in patients randomized to low-dose CT screening and 3.2% of all lung cancers diagnosed after detection of a micronodule.

Overall survival (OS) in the 13 cases where micronodules progressed did not differ significantly from that of other patients with CT-detected lung cancer, as reported online in the .

"Micronodules are very common among lung cancer screened participants and a few are capable of developing into lung cancer," concluded Reginald F. Munden, MD, of Wake Forest Baptist Health in Winston-Salem, North Carolina, and coauthors. "However, following micronodules by annual CT screening surveillance is appropriate and does not impact overall survival or outcome."

"While our study was not designed to assess the current recommendations set by the American College of Radiology [ACR], which recommends that nodules less than or equal to 6 mm do not require active follow-up, in part our findings support this initiative and indicate annual follow-up of small nodules can be performed safely," Munden .

Even though the study evaluated smaller nodules than those covered by the ACR recommendations, the data provided support for the concept that pulmonary micronodules can be followed safely with annual CT imaging, said Stephen Lam, MD, of the University of British Columbia in Vancouver.

If micronodules were considered a positive finding, "then we would be doing a lot of follow-up CT scans before the scheduled annual repeat CT," Lam told 番茄社区app. "The important contribution of this study is that it provided the data and the evidence to show that if you have very small micronodules, we don't need to have early recall for follow-up CT scan."

"This is the first study to show that these nodules do have a very small malignancy risk, but they usually don't develop into lung cancer," he added.

The landmark NLST involved 53,452 individuals with an increased lung cancer risk because of smoking history. They were randomized to have annual lung cancer screening with low-dose CT or standard x-rays. The primary results showed a 20% reduction in the risk of lung cancer death in the CT-screened group.

The NLST protocol defined an isolated 4-mm pulmonary nodule as a negative scan, and patients were followed with repeat annual chest imaging. Munden and colleagues analyzed the NLST data to determine the prevalence and malignant potential of micronodules and to determine the appropriateness of the 4-mm classification.

Their analysis was limited to the 26,722 study participants assigned to CT. Of those, 11,326 (42%) had at least one CT scan that revealed a micronodule. Almost half of the 11,326 patients had at least one positive CT scan, and 409 (3.6%) patients subsequently had a diagnosis of lung cancer (irrespective of the association with the micronodule).

The authors found that 13 of the 409 patients had lung cancer that evolved from a micronodule, representing:

• 1.2% of all lung cancers diagnosed in the CT arm (13 of 1,089)
• 0.11% of the 11,326 micronodules detected in the CT arm
• 0.23% of the 5,560 patients who had a micronodule and at least one positive CT scan

A survival analysis showed no significant difference in OS between patients whose cancer arose from malignant progression of a micronodule and those whose cancers did not (hazard ratio 1.73, 95% CI 0.54-5.52).

Munden and colleagues acknowledged some limitations of the analysis. More than a third (369 of 1,089) of lung cancers diagnosed in the CT arm occurred after CT screening had ended; exclusion of those patients could affect the overall analysis. Additionally, assessments of nodule diameter, derived from CT slices, were not precise.

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