Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts

• Published in: Cancer treatment and research communications Vol. 29; p. 100486
• Main Authors: Burks, Eric J., Zhang, Jiarui, Sullivan, Travis B., Shi, Xingyi, Sands, Jacob M., Regis, Shawn M., McKee, Brady J., McKee, Andrea B., Zhang, Sherry, Liu, Hanqiao, Liu, Gang, Spira, Avrum, Beane, Jennifer, Lenburg, Marc E., Rieger-Christ, Kimberly M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 2021; Elsevier
• Subjects: Adenocarcinoma of Lung - diagnosis; Adenocarcinoma of Lung - diagnostic imaging; Adenocarcinoma of Lung - mortality; Adenocarcinoma of Lung - pathology; Aged; Cohort Studies; CTLS; Early Detection of Cancer; Female; Gene Expression - genetics; Humans; Low malignant potential adenocarcinoma; Lung Neoplasms - diagnosis; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Overdiagnosis; Risk Assessment; RNA sequencing; Screen; Survival Analysis; Tomography, X-Ray Computed - methods; RNA sequencing; Low malignant potential adenocarcinoma; Overdiagnosis; Screen; CTLS
• ISSN: 2468-2942; 2468-2942
• DOI: 10.1016/j.ctarc.2021.100486

Although three randomized control trials have proven mortality benefit of CT lung cancer screening (CTLS), <5% of eligible US smokers are screened. Some attribute this to fear of harm conveyed at shared decision visits, including the harm of overdiagnosis/overtreatment of indolent BAC-like adenocarcinoma. Since the frequency of indolent cancers has not been compared between CTLS and routinely detected cohorts, we compare pathology and RNA expression of 86 NCCN high-risk CTLS subjects to 83 high-risk (HR-R) and 51 low-risk (LR-R) routinely detected patients. Indolent adenocarcinoma was defined as previously described for low malignant potential (LMP) adenocarcinoma along with AIS/MIA. Exome RNA sequencing was performed on a subset of high-risk (CTLS and HR-R) FFPE tumor samples. Indolent adenocarcinoma (AIS, MIA, and LMP) showed 100% disease-specific survival (DSS) with similar frequency in CTLS (18%) and HR-R (20%) which were comparatively lower than LR-R (33%). Despite this observation, CTLS exhibited intermediate DSS between HR-R and LR-R (5-year DSS: 88% CTLS, 82% HR-R, & 95% LR-R, p = 0.047), possibly reflecting a 0.4 cm smaller median tumor size and lower frequency of tumor necrosis compared to HR-R. WGCNA gene modules derived from TCGA lung adenocarcinoma correlated with aggressive histologic patterns, mitotic activity, and tumor invasive features, but no significant differential expression between CTLS and HR-R was observed. CTLS subjects are at no greater risk of overdiagnosis from indolent adenocarcinoma (AIS, MIA, and LMP) than risk-matched patients whose cancers are discovered in routine clinical practice. Improved outcomes likely reflect detection and treatment at smaller size.