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)

Int J Cancer. 2017 Mar 15;140(6):1280-1292. 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).

Keywords: computed tomography; lung cancer screening; national lung screening trial; simulation model; tumor size.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • 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
  • Computer Simulation
  • Early Detection of Cancer*
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Proportional Hazards Models
  • Radiography, Thoracic
  • Remission Induction
  • SEER Program
  • Sex Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Tumor Burden