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)

Abstract

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).

Incidence and Prognosis Nomogram of Small Solitary Lung Cancer (≤2 cm) With Extra-Thoracic Metastasis at Initial Diagnosis:A Population-Based Study

“…In the present study, we also noted that the lung cancer in females had a better prognosis, which is consistent with previous studies. [18][19][20] In addition, we found the patients with the main bronchus as the primary tumor site and liver metastasis had a worse prognosis, which is also consistent with previous studies. 21,22 Moreover, SCLC has been widely recognized with high malignancy and early extensive brain metastases in lung cancer, and reduced responsiveness to therapy.…”

Surgery or Non-surgical Treatment of ≤8 mm Non-small Cell Lung Cancer: A Population-Based Study

“…Hattori reported 10.6% of nodal involvement and 15.1% of recurrence in the subcentimeter pure-solid NSCLC ( 9 ), which indicates that radiological solid lesions with a size of ≤1 cm should be positively treated, regardless of their small size. Goldwasser reported that 32.1% of male and 24.2% of female NSCLC patients were found to have distant metastatic disease with diameter of primary site ≤15 mm ( 36 ). He then established a mathematical model to estimate the tumor size at cure threshold based on the SEER database, and a size of 5–15 mm was recommended for intervention before progression to an incurable disease ( 36 ).…”

“…Goldwasser reported that 32.1% of male and 24.2% of female NSCLC patients were found to have distant metastatic disease with diameter of primary site ≤15 mm ( 36 ). He then established a mathematical model to estimate the tumor size at cure threshold based on the SEER database, and a size of 5–15 mm was recommended for intervention before progression to an incurable disease ( 36 ). From a prospective standpoint, we suggest that both indication and eligibility for surgery should be actively evaluated for nodules ≤8 mm, especially for those with a high pretest probability of malignancy.…”

<p>Multi-Window CT Based Radiological Traits for Improving Early Detection in Lung Cancer Screening</p>

“…9 Meanwhile, the fact that the majority of nonsmall cell lung cancers (NSCLCs) in the NLST were treated when they were greater in size than the curable threshold poses a diagnostic and management challenge. 10 There is a need for early, precise detection tools to identify malignant tumors at smaller sizes within the curable threshold in order to apply LDCT to maximize the benefits of lung cancer screening.…”