Estimation of the tumor size at cure threshold among aggressive non‐small cell lung cancers (NSCLCs): evidence from the surveillance, epidemiology, and end results (SEER) program and the national lung screening trial (NLST)

• Published in: International journal of cancer 2017-03, Vol.140 (6), p.1280-1292
• Main Author: Goldwasser, Deborah L.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Cancer; Carcinoma, Non-Small-Cell Lung - diagnostic imaging; Carcinoma, Non-Small-Cell Lung - epidemiology; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - therapy; computed tomography; Computer Simulation; Early Detection of Cancer; Epidemiology; Female; Follow-Up Studies; Health risk assessment; Humans; Kaplan-Meier Estimate; Lung cancer; lung cancer screening; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - epidemiology; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Male; Medical research; Middle Aged; Mortality; national lung screening trial; Neoplasm Invasiveness; Proportional Hazards Models; Radiography, Thoracic; Remission Induction; SEER Program; Sex Factors; simulation model; Surveillance; Tomography, X-Ray Computed; Treatment Outcome; Tumor Burden; tumor size
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.30548

The National Lung Screening Trial (NLST) demonstrated that non‐small cell lung cancer (NSCLC) mortality can be reduced by a program of annual CT screening in high‐risk individuals. However, CT screening regimens and adherence vary, potentially impacting the lung cancer mortality benefit. We defined the NSCLC cure threshold as the maximum tumor size at which a given NSCLC would be curable due to early detection. We obtained data from 518,234 NSCLCs documented in the U.S. SEER cancer registry between 1988 and 2012 and 1769 NSCLCs detected in the NLST. We demonstrated mathematically that the distribution function governing the cure threshold for the most aggressive NSCLCs, G(x|Φ = 1), was embedded in the probability function governing detection of SEER‐documented NSCLCs. We determined the resulting probability functions governing detection over a range of G(x|Φ = 1) scenarios and compared them with their expected functional forms. We constructed a simulation framework to determine the cure threshold models most consistent with tumor sizes and outcomes documented in SEER and the NLST. Whereas the median tumor size for lethal NSCLCs documented in SEER is 43 mm (males) and 40 mm (females), a simulation model in which the median cure threshold for the most aggressive NSCLCs is 10 mm (males) and 15 mm (females) best fit the SEER and NLST data. The majority of NSCLCs in the NLST were treated at sizes greater than our median cure threshold estimates. New technology is needed to better distinguish and treat the most aggressive NSCLCs when they are small (i.e., 5–15 mm). What's new? The majority of aggressive non‐small cell lung cancers (NSCLCs) are detected only after the tumor has reached an incurable size, significantly limiting the mortality benefit of computed tomography (CT) screening. Here, using novel statistical methodology, the NSCLC cure threshold distribution for the most aggressive tumors detected in the National Lung Screening Trial (NLST) was estimated and compared to outcomes documented in the Surveillance, Epidemiology and End Results (SEER) cancer registry. SEER and NLST data were highly consistent with a median cure threshold for aggressive NSCLCs of 10–15 mm in size, emphasizing the need for new technologies capable of accurately detecting and diagnosing small NSCLCs.