title: Differences in Patient Outcomes of Prevalence, Interval, and Screen-Detected Lung Cancers in the CT Arm of the National Lung Screening Trial.
abstract: Lung cancer screening identifies cancers with heterogeneous behaviors. Some lung cancers will be identified among patients who had prior negative CT screens and upon follow-up scans develop a de novo nodule that was determined to be cancerous. Other lung cancers will be identified among patients who had one or more prior stable positive scans that were not determined to be lung cancer (indeterminate pulmonary nodules), but in follow-up scans was diagnosed with an incidence lung cancer. Using data from the CT arm of the National Lung Screening Trial, this analysis investigated differences in patient characteristics and survival endpoints between prevalence-, interval-, and screen-detected lung cancers, characterized based on sequence of screening results. Lung cancers immediately following a positive baseline (T0), and prior to the T1 screen, formed the prevalence cohort. Interval cancers were diagnosed following a negative screen at any time point prior to the next screening round. Two cohorts of screen-detected lung cancers (SDLC) were identified that had a baseline positive screen that was that was not determined to be lung cancer (i.e., an indeterminate pulmonary nodule), but in follow-up scans was diagnosed with an incidence lung cancer 12 (SDLC1) or 24 (SDLC2) months later. Two other incidence cohorts had screen-detected lung cancers that had baseline negative screen and upon follow-up scans developed a de novo nodule determined to be cancerous at 12 (SDLC3) or 24 (SDLC4) months later. Differences in patient characteristics, progression-free survival (PFS), and overall survival (OS) were assessed. The lung cancer-specific death rate was higher for SDLC3/SDLC4 compared to SDLC1/SDLC2 lung cancers (136.6/1,000 person-years vs. 71.3/1,000 person-years, P < 0.001). Moreover, PFS and OS were significantly lower for SDLC3/SDLC4 compared to SDLC1/SDLC2 (P < 0.004; P < 0.002, respectively). The findings were consistent when stratified by stage and histology. Multivariable Cox proportional models revealed that the SDLC3/SDLC4 case groups were associated with significantly poorer PFS (HR = 1.89; 95% CI 1.31-2.74) and OS (HR = 1.80; 95% CI 1.21-2.67) compared to SDLC1/SDLC2 lung cancers (HR = 1.00). Lung cancer patients who develop a de novo nodule that determined to be cancerous (i.e., at least one negative CT screen prior to cancer diagnosis) had poorer survival outcomes compared to patients who had at least one positive screen prior to cancer diagnosis. As such, the observation that de novo screen-detected are associated with poorer survival could be attributed to faster growing, more aggressive cancers that arose from a lung environment previously lacking focal abnormalities.
authors: Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
authors: Matthew B
authors: http://orcid.org/0000-0003-3241-3216
authors: MB
authors: Schabath
authors: Thoracic Program, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, United States of America.
authors: Pierre P
authors: PP
authors: Massion
authors: Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
authors: Zachary J
authors: ZJ
authors: Thompson
authors: Department of Biomedical Informatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
authors: Steven A
authors: SA
authors: Eschrich
authors: Department of Cancer Imaging, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
authors: Yoganand
authors: Y
authors: Balagurunathan
authors: Department of Computer Science and Engineering; University of South Florida, Tampa, Florida, United States of America.
authors: Dmitry
authors: D
authors: Goldof
authors: Department of Radiological Sciences; David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
authors: Denise R
authors: DR
authors: Aberle
authors: Department of Cancer Imaging, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
authors: Robert J
authors: RJ
authors: Gillies
mesh_terms: D000368:Aged; D003710:Demography; D018572:Disease-Free Survival; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009367:Neoplasm Staging; D015995:Prevalence; D016016:Proportional Hazards Models; D012306:Risk; D012907:Smoking; D014057:Tomography, X-Ray Computed