Occurrence and lung cancer probability of new solid nodules at incidence screening with low-dose CT: analysis of data from the randomised, controlled NELSON trial.
BACKGROUND
US guidelines now recommend lung cancer screening with low-dose CT for high-risk individuals. Reports of new nodules after baseline screening have been scarce and are inconsistent because of differences in definitions used. We aimed to identify the occurrence of new solid nodules and their probability of being lung cancer at incidence screening rounds in the Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON).


METHODS
In the ongoing, multicentre, randomised controlled NELSON trial, between Dec 23, 2003, and July 6, 2006, 15 822 participants who had smoked at least 15 cigarettes a day for more than 25 years or ten cigarettes a day for more than 30 years and were current smokers, or had quit smoking less than 10 years ago, were enrolled and randomly assigned to receive either screening with low-dose CT (n=7915) or no screening (n=7907). From Jan 28, 2004, to Dec 18, 2006, 7557 individuals underwent baseline screening with low-dose CT; 7295 participants underwent second and third screening rounds. We included all participants with solid non-calcified nodules, registered by the NELSON radiologists as new or smaller than 15 mm(3) (study detection limit) at previous screens. Nodule volume was generated semiautomatically by software. We calculated the maximum volume doubling time for nodules with an estimated percentage volume change of 25% or more, representing the minimum growth rate for the time since the previous scan. Lung cancer diagnosis was based on histology, and benignity was based on histology or stable size for at least 2 years. The NELSON trial is registered at trialregister.nl, number ISRCTN63545820.


RESULTS
We analysed data for participants with at least one solid non-calcified nodule at the second or third screening round. In the two incidence screening rounds, the NELSON radiologists registered 1222 new solid nodules in 787 (11%) participants. A new solid nodule was lung cancer in 49 (6%) participants with new solid nodules and, in total, 50 lung cancers were found, representing 4% of all new solid nodules. 34 (68%) lung cancers were diagnosed at stage I. Nodule volume had a high discriminatory power (area under the receiver operating curve 0·795 [95% CI 0·728-0·862]; p<0·0001). Nodules smaller than 27 mm(3) had a low probability of lung cancer (two [0·5%] of 417 nodules; lung cancer probability 0·5% [95% CI 0·0-1·9]), nodules with a volume of 27 mm(3) up to 206 mm(3) had an intermediate probability (17 [3·1%] of 542 nodules; lung cancer probability 3·1% [1·9-5·0]), and nodules of 206 mm(3) or greater had a high probability (29 [16·9%] of 172 nodules; lung cancer probability 16·9% [12·0-23·2]). A volume cutoff value of 27 mm(3) or greater had more than 95% sensitivity for lung cancer.


CONCLUSIONS
Our study shows that new solid nodules are detected at each screening round in 5-7% of individuals who undergo screening for lung cancer with low-dose CT. These new nodules have a high probability of malignancy even at a small size. These findings should be considered in future screening guidelines, and new solid nodules should be followed up more aggressively than nodules detected at baseline screening.


BACKGROUND
Zorgonderzoek Nederland Medische Wetenschappen and Koningin Wilhelmina Fonds Kankerbestrijding.
University of Groningen, University Medical Center Groningen, Center for Medical Imaging-North East Netherlands, Groningen, Netherlands.
Joan E
JE
Walter
University of Groningen, University Medical Center Groningen, Center for Medical Imaging-North East Netherlands, Groningen, Netherlands.
Marjolein A
MA
Heuvelmans
University Medical Center Utrecht, Department of Radiology, Utrecht, Netherlands.
Pim A
PA
de Jong
University of Groningen, University Medical Center Groningen, Center for Medical Imaging-North East Netherlands, Groningen, Netherlands; Department of Radiology, Groningen, Netherlands.
Rozemarijn
R
Vliegenthart
University of Groningen, University Medical Center Groningen, Center for Medical Imaging-North East Netherlands, Groningen, Netherlands; Department of Radiology, Groningen, Netherlands.
Peter M A
PMA
van Ooijen
Department of Radiology, Groningen, Netherlands.
Robin B
RB
Peters
Department of Public Health, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.
Kevin
K
Ten Haaf
Department of Public Health, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.
Uraujh
U
Yousaf-Khan
Department of Public Health, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.
Carlijn M
CM
van der Aalst
Department of Epidemiology, Groningen, Netherlands.
Geertruida H
GH
de Bock
University Medical Center Utrecht, Department of Radiology, Utrecht, Netherlands.
Willem
W
Mali
Department of Pulmonary Diseases, Groningen, Netherlands.
Harry J M
HJM
Groen
Department of Public Health, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.
Harry J
HJ
de Koning
University of Groningen, University Medical Center Groningen, Center for Medical Imaging-North East Netherlands, Groningen, Netherlands. Electronic address: m.oudkerk@umcg.nl.
Matthijs
M
Oudkerk
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology; D000368:Aged; D001530:Belgium / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D055613:Multiple Pulmonary Nodules / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000473:pathology*; D009367:Neoplasm Staging; D009426:Netherlands / Q000453:epidemiology; D011336:Probability; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology; D012984:Software; D014057:Tomography, X-Ray Computed / Q000379:methods*