From the Journals

Watch and wait often better than resecting in ground-glass opacities


Key clinical point: Three-year observation of ground-glass opacities is an appropriate management protocol for patients with a CTR greater than zero, although more may be necessary for those with zero ratio.

Major finding: Of 226 patients with ground-glass opacity lesions 3 cm or less in size, 124 had resection, 57 required no further follow-up, and 45 continue to receive follow-up.

Data source: Long-term study of 226 patients with pure or mixed ground-glass opacities of 3 cm or less given regular CT imaging between 2000 and 2005.

Disclosures: Neither the investigators nor the editorial writer had any relevant disclosures.

Eric Gartman, MD, FCCP, comments: This study provides further support that the biology of ground-glass and part-solid nodules is different than fully solid nodules – and we should not be in a rush to resect these lesions. While the recommendations are likely to evolve over time as more information becomes available, this conservative approach toward nonsolid nodules is currently adopted in the Lung-RADS guidelines.

Dr. Eric J. Gartman
Dr. Eric J. Gartman
Invasive action on these nodules is based on solid component size and growth, and usually the interval for following them once they have demonstrated early stability is annually. The optimal duration of follow-up is still in question, but ceasing follow-up for all part-solid nodules at 3 years likely is premature given the variable slow progression these nodules exhibit.



Three years of follow-up is adequate for partially solid ground-glass opacity lesions that do not progress, while pure ground-glass opacity lesions that show no progression may require further follow-up care, a study suggests.

The results of the study strengthen the argument for taking a “watch and wait” approach, and raise the question of whether patient outcomes can be improved without more precise diagnostic criteria, said study author Shigei Sawada, MD, PhD, a researcher at the Shikoku Cancer Center in Matsuyama, Japan, and his colleagues. They drew these conclusions from performing a long-term outcome investigation of 226 patients with pure or mixed ground-glass opacity lesions shown by CT imaging to be 3 cm or less in diameter.

Once established that the disease has stabilized in a pure or mixed ground-glass opacity lesion, “the frequency of CT examinations could probably be reduced or ... discontinued,” the investigators wrote. The study is published online in Chest (2017;151[2]:308-15).
Because ground-glass opacities often can remain unchanged for years, reflexively choosing resection can result in a patient’s being overtreated. Meanwhile, the use of increasingly accurate imaging technology likely means detection rates of such lesions will continue to increase, leaving clinicians to wonder about optimal management protocols, particularly since several guidance documents include differing recommendations on the timing of surveillance CTs for patients with stable disease.

The study includes 10-15 years of follow-up data on the 226 patients, registered between 2000 and 2005. Across the study, there were nearly twice as many women as men, all with an average age of 61 years. About a quarter had multiple ground-glass opacities; about a quarter also had partially consolidated lesions. Of the 124 patients who’d had resections, all but one was stage IA. The most prominent histologic subtype was adenocarcinoma in situ in 63 patients, followed by 39 patients with minimally invasive adenocarcinomas, and 19 with lepidic predominant adenocarcinomas. Five patients had papillary-predominant adenocarcinomas.

Roughly one-quarter of the cohort did not receive follow-up examinations after 68 months, as their lesions either remained stable or were shown to have reduced in size. Another 45 continued to undergo follow-up examinations.

After initial detection of a pure ground-glass opacity, the CT examination schedule was every 3, 6, and 12 months, and then annually. After detection of a mixed ground-glass opacity, a CT examination was given every 3 months for the first year, then reduced to every 6 months thereafter. In patients with stable disease, the individual clinicians determined whether to obtain additional CT follow-up imaging.

A ground-glass lesion was determined to have progressed if the diameter increased, as it did in about a third of patients; or, if there was new or increased consolidation, as there was in about two-thirds of patients. The table of consolidation/tumor ratios (CTR) used included CTR zero, also referred to as a pure ground-glass lesion; CTR 1-25; CTR 26-50; and CTR equal to or greater than 51. When there were multiple lesions, the largest one detected was the target.
All cases of patients with a CTR of more than zero were identified within 3 years, while 13.6% of patients with a CTR of zero required more than 3 years to identify tumor growth. Aggressive cancer was detected in 4% of patients with a CTR of zero and in 70% of those with a CTR greater than 25% (P less than .001). Aggressive cancer was seen in 46% of those with consolidation/tumor ratios that increased during follow-up and in 8% of those whose tumors increased in diameter (P less than .007). After about 10 years of follow-up after resection, 1.6% of cancers recurred.

There were two deaths from lung cancer among the study’s patients. The first, a 54-year-old man, had an acinar-predominant adenocarcinoma, 5 mm in diameter with a consolidation/tumor ratio of 0.75 that increased during follow-up. The recurrence developed in the mediastinal lymph nodes 51 months after resection surgery. The second patient had a papillary-predominant adenocarcinoma appearing as a pure ground-glass opacity 27 mm in diameter. The consolidation/tumor ratio also increased during follow-up, with recurrences in the bone and mediastinal lymph nodes at 30 months post resectioning.

Neither patient was re-biopsied, and both were diagnosed according to CT imaging alone. There were 13 other patient deaths from non–lung cancer related causes.

Given the 3-year timespan necessary to detect tumor growth in all but the CTR zero group, and the study’s size and long-term nature, the investigators concluded that a follow-up period of 3 years for patients with part-solid lesions “should be adequate.”

By contrast, CHEST recommends CT scans be done for at least 3 years in patients with pure ground-glass lesions and between 3 and 5 years in the other CTR groups with nodules measuring 8 mm or less. The National Comprehensive Cancer Network guideline advises low-dose CT scanning until a patient is no longer eligible for definitive treatment.
Dr. Sawada and his colleagues did not use an exact criterion for tumor growth in their study, such as a precise ratio of increase in size or consolidation, in part because at the time of the study the most common form of CT evaluation was visual inspection; they reported that tumors exhibiting growth most commonly increased between 2 and 3 mm in either size or consolidation. “Evaluations based on visual inspections can be imprecise, and different physicians may arrive at different judgments,” the investigators wrote. “However, [the use of] computer-aided diagnosis systems are not yet commonly applied in clinical practice.”
Although imaging should have guided the decision to resect, according to Dr. Sawada and his coauthors, two-thirds of patients in the study were given the procedure even though their lesions were not shown by CT scans to have progressed. This was done either at the patient’s request, or per the clinical judgment of a physician.

Dr. Frank Detterbeck, surgical director, Yale University
Dr. Frank Detterbeck
Although the study “represents a major advance,” according to Frank C. Detterbeck, MD, FCCP, surgical director of thoracic oncology at Yale University, New Haven, Conn., who wrote an editorial accompanying the study, the results should spur the field to get more specific, and question whether a 3-year window was enough. “This seems counterintuitive given the chance of it becoming an invasive cancer,” Dr. Detterbeck wrote, indicating that not rushing to resection should mean more use of CT. “We should just look at what is already in front of our eyes: the radiographic features of [ground-glass nodules] are highly predictive of biological behavior. It will be hard to do better than this.”

Also becoming more specific about changing CTRs would be helpful in developing management protocols, according to Dr. Detterbeck. “In my opinion, we need to start factoring in the rate of change. A gradual 2 mm increase in size over a period of 5 years may not be an appropriate trigger for resection.”

Neither the investigators nor the editorial writer had any relevant disclosures.

On Twitter @whitneymcknight