NLST to change patient management, practice, experts say

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Unenhanced chest CT lung window image reveals that lingula, right middle lobe, and both lower lobes show patchy, peripheral, rounded, peribronchial ground-glass opacities with air bronchograms.
Image source: American Journal of Roentgenology
The decision of the National Cancer Institute to stop the National Lung Cancer Screening Trial (NLST) promises to have far-reaching impacts. The data could lead to a new approach to lung cancer screening characterized by thoughtful and systematic patient selection. Reimbursement seems possible, and the announcement could fuel chest CT computer-aided detection (CAD) development. But questions about clinical management and costs remain, and data analysis is ongoing.

Last week, the NCI prematurely ceased the NLST after initial results demonstrated that CT screening with at least three annual screens in a high risk population of current and former smokers aged 55 to 74 years conferred a 20 percent drop in lung cancer mortality compared with x-ray screening.

The announcement is spurring clinical conversations about screening and patient management across the U.S.

“[Before this decision] if a patient asked me about screening CT, I would have actively discouraged it and told them screening CT was not ready for prime time. Now my answer would be different,” Greg Otterson, MD, interim co-director of the division of hematology and oncology at the Ohio State University Comprehensive Cancer Center in Columbus, shared with Health Imaging News.

“The NLST results will have a significant impact on public health policy. Exactly who would benefit from CT screening, where that screening should be performed and the frequency and duration of screening are all questions that remain to the determined and will require more careful analysis of the considerable data collected from the NLST over the coming weeks,” offered Denise R. Aberle, MD, professor of radiology and bioengineering at University of California, Los Angeles and national principal investigator for NLST, in an interview with Health Imaging News. Researchers also will review data by gender, race and type of smoking history.

The data certainly reinvigorate the discussion about the role of screening CT, added Ella A. Kazerooni, MD, professor of radiology at the University of Michigan Health System in Ann Arbor and site principal investigator for NLST, in an interview with Health Imaging News.

Indeed, as researchers focus on fuller analysis of the data including results for population subsets, national stakeholders and providers across the U.S. are considering implications of the announcement. The American Cancer Society and the National Comprehensive Cancer Network (NCCN) are working on screening recommendations. NCCN is likely to base its screening recommendations on NSLT criteria: current and former smokers aged 55 to 74 years with a smoking history of at least 30 pack years.

Recommendations should be available in a few months, said Otterson, a member of the NCCN Lung Cancer Screening Guidelines Panel.

CT screening in evolution
NLST was implemented primarily at major medical institutions, all of which had an infrastructure to address positive screens, Aberle pointed out. The trial reported an overall 24 percent rate of positive screen results with the first CT screen, which decreased with subsequent screens. The majority of positive screens were false positives.

Small nodules detected by screening CT will require additional CT studies and possibly PET scans and more invasive biopsies or surgical lung resections. “The diagnostic workup has to be very carefully considered. The follow-up algorithm for a 5 mm lesion and a 1.5 cm lesion will be very different,” noted Otterson. Recommendations for the followup of indeterminate nodules, such as the Fleischner Society guidelines, already exist and provide a good starting point for protocols for assessing individuals with positive screens until analysis of new data revises best practices, explained Aberle.

“Ideally, CT screening should be implemented in practice settings in which current best practice guidelines exist for the performance of low-dose CT screening and judicious followup is practiced.  Screening should be affiliated with providers to whom individuals with positive screens can be referred for thoughtful evaluation,” recommended Aberle.

For example, University of Michigan is evaluating the potential for a high-risk lung cancer clinic. Such a program could include screening CT, offered Kazerooni, and allow for more systematic management of the high-risk population.

Clinical practice not only needs to consider systematic followup but also incorporate judicious selection of individuals for screening.

Otterson envisions the target population fitting a bell-shaped distribution curve. Some patients outside of the NSLT criteria, such as the healthy 49-year-old smoker with a 45 pack year history, probably should be screened, he said. Anxious non-smokers as well as patients who will not tolerate diagnostic followup will be more challenging. For example, a patient with advanced COPD would not tolerate followup surgery or radiation; the knowledge of lung cancer may not be helpful, shared Otterson. The oncologist anticipates limits on screening for low-risk and high-risk patients; however, such limits are not yet defined.

Impact on radiology
If screening CT is accepted as a clinical tool, CT providers will need to adapt. On the plus side, with a healthy network of CT scanners across the country the U.S. already has capacity to handle screening CT. In addition, the screening study does not require oral or IV contrast and is short relative to diagnostic CT studies. Nor is there a shortage of qualified reviewers, noted Kazerooni.

But radiologists may need to make other adjustments. “They’ll need to make sure the right patients are coming to them, which requires communication with referring providers,” explained Kazerooni. “[Screening CT entails] looking for very small nodules. It takes thoughtful, systematic interpretation.”

Radiologists can expect to participate in both downstream conversations with colleagues in pulmonary medicine and oncology as well as upstream conversations with primary care physicians as the entire community grapples with the data and considers a new model.

“It will be up [to radiologists] to ensure standardization of followup, both for indeterminate nodules as well as other findings—like lesions of the thyroid, liver and kidney as well as cardiovascular and other abnormalities—that may be detected,” offered Aberle.

The drive for standardization and uniformity coupled with increased utilization could fuel technology innovation. “It could drive the development and potential reimbursement for chest CT CAD,” predicted Kazerooni.

Cost issues
As researchers and clinicians wrangle with the clinical implications of NLST, healthcare stakeholders also are considering economic ramifications. A major secondary aim of the trial is a cost-effectiveness analysis, shared Aberle. Researchers obtained quality of life measures for participants, detailed data on medical resource utilization for positive screens and screens that detected other findings and information about the management and outcomes of individuals with lung cancers.

“All of this information will be tremendously valuable to the NLST investigators and others as public health policy is crafted and we secure Medicare and insurance reimbursement for CT screening,” explained Aberle, who predicted that results of the cost-effectiveness analysis should be available in 2011.

The continuing data analysis will bring new findings and offer new models, but a few results are clear. “We know that the data demonstrated a benefit to 55 to 74 year old current and former smokers, and the positive finding of the 20 percent decrease in mortality cannot be overemphasized,” concluded Kazerooni.