In the current edition of Academic Radiology, Hsu et al. ( ) evaluate potential improvement in the detection of lesions in the spectrum of adenocarcinoma (LSAs) by first proposing modifications of current ACR Lung-RADS criteria and then retrospectively applying these to a screened cohort of Asian individuals including both ever and never-smokers, between 40 and 80years of age. The authors’ contention is that by broadly expanding the number of eligible individuals for screening while simultaneously focusing on the most suspicious lesions, identifying adenocarcinomas will be significantly increased necessitating a reappraisal of current management guidelines.
For this purpose, an Asian cohort of 1978 individuals (including 72.8% never-smokers), were retrospectively evaluated comparing criteria from the National Lung Screening Trial (NLST) ( ) and ACR Lung-RADS to modified Lung-RADS criteria ( ) as follows: Lung-RADS categories 2 and 3 were reclassified into subcategories 2A/B/C and 3A/B/C, respectively, with 2C defined as pure groundglass nodules <20mm, and 3B defined as part solid lesions ≥6mm with solid components >6mm, without altering morphologic characteristics ( ). Using 2C as a cut-off then, modified Lung-RADS criteria proved to have greater predictive ability for identifying LSAs compared to either NLST or current Lung-RADS criteria ( p < .001) with sensitivity of 100% (95% CI 89.1%, 100%), specificity of 89.3% (95% CI 87.9%, 90.6%) and an area under the curve (AUC) of 0.973 (95% CI 0.965–0.980), respectively.
Similarly, using 3B as a cut-off resulted in an improved sensitivity of 95.0% (95% CI 75.1%, 99.9%), and specificity of 97.8% (95% CI 97.1%, 98.4%) for detecting invasive adenocarcinomas (IAs). While the AUC of .992, (95% CI 0.987–0.995) proved superior to the AUC using NLST criteria, however, no significant difference was noted comparing the current AUC of Lung-RADS to modified Lung-RADS criteria ( p = .155).
The authors’ findings are of considerable interest and clearly provocative, however numerous questions arise specifically as to what relates to the current Western Low-dose computed tomorgraphy (LDCT) screening programs, especially to ACR- Lung-RADS. What is the impact of these data on current LDCT screening protocols? What are the implications for the management of earlier “indolent” lesions in the adenocarcinoma spectrum—especially 2C/pure groundglass nodules including atypical adenomatous hyperplasia (AAH), adenocarcinoma-in-situ (AIS) and minimally invasive adenocarcinoma (MIA)? What of the inclusion of never-smokers as represented in nearly two-thirds of the present study? Finally, what are the implications for incidentally identified nodules among high prevalence populations evaluated outside screening programs?
To answer these questions one requires further evaluation of the author’s findings ( ). Of 1978 individuals screened, 166 (8.3%) had nodules classified as 2C of which only 11 (6.6%) had documented LSAs, while only 7 (0.35%) individuals had nodules classified as 3B of which only 2 (28.5%) proved to have LSAs. Of 36 subjects with documented biopsies, four proved to have benign lesions: all the remaining 32 cases (including 30 nonsmokers) proved to be LSAs, subsequently followed for an average of only 1.6 +/− 0.5years. Of these only 20 (62.5%) proved to be IAs . More importantly , of 11 2C lesions (<20 cm) fewer than half, 5 (45.5%), were interpreted as invasive cancers, although this included four MIAs. Of the remaining six cases, there were three cases each of AAH and AIS respectively. Importantly, all 11 2C cases proved to be stage 1 lesions .
These results indicate that even in high prevalence populations the overall number of early stage lesions remains exceedingly small, consistent with numerous prior screening studies in the United States, Europe, and Asia, in part limiting concern of their overall clinical impact ( ). As important, the author’s proposed modifications fail to improve reliable differentiation among earlier stage lesions, a problem seriously compounded by the indication for complete surgical resection to diagnose AIS or MIA ( ). Also pertinent is the lack of specified indications for obtaining biopsies.
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