Lung Cancer Screening Focuses on Part-Solid Nodules

NEW YORK—Lung cancer screening investigators are sharpening their focus on the small, only partly solid nodules they observe on initial and follow-up spiral CT. Recent data show that these nodules are more often malignant than completely nonsolid or totally solid nodules, said Claudia I. Henschke, MD, PhD, chief of the Division of Chest Imaging, Weill Medical College of Cornell University.

"We want to identify which nodules have a high likelihood of malignancy. We don’t need to talk about all nodules, but tease out one subcategory, the part-solid, that needs a more aggressive workup," Dr. Henschke said at the Fifth International Conference on Screening for Lung Cancer.

Terminology in early lung cancer detection is evolving. A "nodule" refers to any focal, nonlinear opacity, of which there are two types: solid and focally translucent "subsolid" nodules (previously called "ground glass opacities" because of their appearance on CT).

Subsolid nodules can be further subdivided into those that are completely nonsolid and those that are "part-solid"—the ones that have been shown to be more frequently malignant.

In a study submitted for publication, Dr. Henschke and her colleagues found that nonsolid and solid nodules have a similar frequency of malignancy—about 18% for each. The part-solid nodules have a frequency of malignancy of approximately 60%, or a 3.5-fold higher incidence. "It’s a big difference," she said. "Therefore, the workup of those nodules in a lung cancer screening program has to be different."

Workup Only the Beginning

Workup is only the beginning. Because these part-solid nodules are found early and small, they may represent a very fertile field for chemoprevention, chemotherapy, or surgery. Rather than targeting all nodules, she said, the subsolid lesions could be singled out to more efficiently and quickly evaluate response to specific chemopreventive interventions, or in evaluations of limited resection vs lobectomy.

"These highly malignant lesions make an attractive target for chemoprevention," said James L. Mulshine, MD, chief of the Intervention Section at the NCI’s Center for Cancer Research. "But this is a disease for which there is no validated effective chemoprevention at this time, which is a challenge."

One specific challenge is that standard procedure based on finding large primary lesions, measured in centimeters, will not likely translate into the setting of spiral CT screening of asymptomatic, high-risk populations, where much smaller lesions, measured in millimeters, may be found.

"There may be different tools that turn out to be valuable in early settings that would be totally inappropriate to apply in advanced settings," Dr. Mulshine said. "We are going to have to revalidate everything we do. This is a whole new waterfront of targets."

A number of questions are on the table. Larger subsolid nodules are suitable candidates for biopsy, but there is still no broad consensus on whether certain subtypes, when still small, should be biopsied or simply watched.

Investigators are hoping to form a broad consensus on how to structure studies so that data can be pooled in a large, international registry. Plans to build this registry are under discussion. "We need to get a registry and determine the final diagnoses of nodules found on screening and to verify that there is a discrepant frequency of malignancy among the part-solid ones," Dr. Henschke said.

A good deal of these data may already be available. Researchers at Weill Cornell have already screened approximately 3,000 patients and are participating in a larger screening program of 10,000 high-risk patients, being done under the auspices of NY-ELCAP, a consortium of 11 institutions in New York State.

At least 8,000 more patients are being evaluated in specific institutions in the United States and abroad, while Japanese researchers alone have screened more than 15,000 patients.

"I think we are going to be able to pool quite a lot of data, and really populate this registry, and perhaps answer a lot of these questions," said David Yankelevitz, MD, co-director of the Lung Cancer Screening Center, Weill Cornell. "The question remains, how do we proceed, and do we have enough information to even contemplate a randomized, clinical trial?"

Researchers will share further insights on part-solid nodules at the next International Conference on Screening for Lung Cancer, which is scheduled for April 5-7, 2002.