Uneven Distribution of Cancer Histology in the National Lung Screening Trial

The National Lung Screening Trial reported a 20% lower mortality due to lung cancer in the patients screened with low-dose computed tomography (LDCT) compared with plain chest radiography (XRAY). A hypothesis was raised that LDCT should detect more cases of all tissue types or else the distribution of tissue types should be equal between groups. Data were extracted regarding the tissue types of lung cancer and presenting stages from the 2011 NSLT report. A total of 1,993 cases of tissue diagnosed lung cancer were reported, 1,054 for the LDCT group and 939 for the XRAY group. Two tissue types were more prevalent in the XRAY group: small cell carcinomas (16.9% versus 13%; P < 0.05) and other non-small cell (ONSC) carcinomas (16.8% versus 12.4%; P < 0.05). The ONSC category excluded the usual non-small cell tissue types: adenocarcinomas, squamous, and large cell carcinomas and did include other known biologically unfavorable tissue types. The XRAY group also had a disproportionately large number of stage IV small cell and ONSC tumors (P < 0.05 for ONSC). Bronchoalveolar cell carcinomas were more prevalent in the LDCT group (10.4% versus 3.7%, P < 0.05), likely reflecting greater sensitivity for detection. In summary, this review found uneven distribution of cases and higher preponderance of stage IV tumors for 2 adverse tissue types in the XRAY group. The results are consistent with greater severity of disease in the XRAY group with potential for length time bias and reduced mortality benefit from LDCT screening.