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Screening for lung cancer is not currently recommended, even in persons at high risk for this condition. Most patients with lung cancer present with symptomatic disease that is usually at an incurable, advanced stage. The recently reported NLST (National Lung Screening Trial) showed a 20% decrease in deaths from lung cancer in high-risk persons undergoing screening with low-dose computed tomography of the chest compared with chest radiography. The high-risk group included in the trial comprised asymptomatic persons aged 55 to 74 years, with smoking history of at least 30 pack-years. Screening with low-dose computed tomography detected more cases of early-stage lung cancer and fewer cases of advanced-stage cancer, confirming that screening has shifted the stage of cancer at diagnosis and provides more persons with the opportunity for curative treatment. Although computed tomography screening has risks and limitations, the 20% decrease in deaths is the single most dramatic decrease ever reported for deaths from lung cancer, with the possible exception of smoking cessation. Physicians should offer computed tomography screening for lung cancer to patients who fit the high-risk profile defined in the NLST.

Prognosis of lung cancer is markedly improved when cancers are resected in early stages (particularly in stage I). Previous investigations failed to show benefit with use of chest radiographs or sputum cytologies to screen for lung cancer among high-risk populations. More recently, computed tomography (CT) has been used as a screening technique and appears to detect lung cancer at earlier stages (e.g., stage I) compared with usual clinical practice. However, whether screening CT reduces death from lung cancer has not been clarified. This review examines the problem presented by lung cancer, the issues presented by screening, and the results of past and recent studies of lung cancer screening.

Background: Lung cancer typically exhibits symptoms only after the disease has spread, making cure unlikely. Because early-stage disease can be successfully treated, a screening technique that can detect lung cancer before it has spread might be useful in decreasing lung cancer mortality., Objectives: In this article, we review the evidence for and against screening for lung cancer with low-dose CT and offer recommendations regarding its usefulness for asymptomatic patients with no history of cancer., Results: Studies of lung cancer screening with chest radiograph and sputum cytology have failed to demonstrate that screening lowers lung cancer mortality rates. Published studies of newer screening technologies such as low-dose CT and "biomarker" screening report primarily on lung cancer detection rates and do not present sufficient data to determine whether the newer technologies will benefit or harm. Although researchers are conducting randomized trials of low-dose CT, results will not be available for several years. In the meantime, cost-effectiveness analyses and studies of nodule growth are considering practical questions but producing inconsistent findings., Conclusions: For high-risk populations, no screening modality has been shown to alter mortality outcomes. We recommend that individuals undergo screening only when it is administered as a component of a well-designed clinical trial with appropriate human subjects' protections.

Purpose: To retrospectively evaluate the computed tomography (CT)-determined size, morphology, location, morphologic change, and growth rate of incidence and prevalence lung cancers detected in high-risk individuals who underwent annual chest CT screening for 5 years and to evaluate the histologic features and stages of these cancers., Materials and Methods: The study was institutional review board approved and HIPAA compliant. Informed consent was waived. CT scans of 61 cancers (24 in men, 37 in women; age range, 53-79 years; mean, 65 years) were retrospectively reviewed for cancer size, morphology, and location. Forty-eight cancers were assessed for morphologic change and volume doubling time (VDT), which was calculated by using a modified Schwartz equation. Histologic sections were retrospectively reviewed., Results: Mean tumor size was 16.4 mm (range, 5.5-52.5 mm). Most common CT morphologic features were as follows: for bronchioloalveolar carcinoma (BAC) (n = 9), ground-glass attenuation (n = 6, 67%) and smooth (n = 3, 33%), irregular (n = 3, 33%), or spiculated (n = 3, 33%) margin; for non-BAC adenocarcinomas (n = 25), semisolid (n = 11, 44%) or solid (n = 12, 48%) attenuation and irregular margin (n = 14, 56%); for squamous cell carcinoma (n = 14), solid attenuation (n = 12, 86%) and irregular margin (n = 10, 71%); for small cell or mixed small and large cell neuroendocrine carcinoma (n = 7), solid attenuation (n = 6, 86%) and irregular margin (n = 5, 71%); for non-small cell carcinoma not otherwise specified (n = 5), solid attenuation (n = 4, 80%) and irregular margin (n = 3, 60%); and for large cell carcinoma (n = 1), solid attenuation and spiculated shape (n = 1, 100%). Attenuation most often (in 12 of 21 cases) increased. Margins most often (in 16 of 20 cases) became more irregular or spiculated. Mean VDT was 518 days. Thirteen of 48 cancers had a VDT longer than 400 days; 11 of these 13 cancers were in women., Conclusion: Overdiagnosis, especially in women, may be a substantial concern in lung cancer screening., ((c) RSNA, 2007.)

Background: A blood test for non-small cell lung cancer (NSCLC) may be a valuable tool for use in a comprehensive lung cancer screening strategy. Here we report the potential of autoantibody profiling to detect early-stage and occult NSCLC., Methods: T7-phage NSCLC cDNA libraries were screened with patient plasma to identify phage-expressed proteins recognized by tumor-associated antibodies. Two hundred twelve immunogenic phage-expressed proteins, identified from 4000 clones, were statistically ranked for their individual reactivity with 23 stage I cancer patient and 23 risk-matched control samples. All 46 samples were used as a training set to define a combination of markers that were best able to distinguish patient from control samples; this set of classifiers was then examined using leave-one-out cross-validation. Markers were then used to predict probability of disease in 102 samples from the Mayo Clinic CT Screening Trial (six prevalence cancer samples, 40 drawn 1 to 5 years before diagnosis, and 56 risk-matched controls)., Results: Measurements of the five most predictive antibody markers in 46 cases and controls were combined in a logistic regression model that yielded area under the receiver operating characteristics curve of 0.99; leave-one-out validation achieved 91.3% sensitivity and 91.3% specificity. In testing this marker set with samples from the Mayo Clinic Lung Screening Trial, we correctly predicted six of six prevalence cancers, 32 of 40 cancers from samples drawn 1 to 5 years before radiographic detection on incidence screening, and 49 of 56 risk-matched controls., Conclusions: Antibody profiling may be a useful tool for early detection of NSCLC.

Past lung cancer screening trials in the United States with chest X-ray and sputum cytology were not able to show any decrease in lung cancer mortality; however, these trials are over 20 years old. Recent follow-up of the Mayo Lung Project showed a better survival from lung cancer in the screened arm, but no difference in overall mortality, suggesting an overdiagnosis of nonfatal cancers. Recent reports of low radiation dose spiral computed tomography (CT) chest screening for lung cancer have shown that CT screening detects cancers at a smaller size than chest X-rays. To date, there have been no randomized trials of CT versus observation or chest radiographs for screening purposes. All data available thus far on CT screening are from phase II proof-of-principle trials. The major limitations of CT screening, discussed here, include (a) a high rate of nodule detection: over 50% of participants will have at least one noncalcified nodule; (b) resulting follow-up CT scans, associated with increased costs; (c) cost and morbidity of biopsy or resection of benign noncalcified nodule (20-25% of such procedures in several trials); and (d) a small, but difficult to quantify, risk of cancer associated with multiple follow-up CT scans.

Objective: The objective of our study was to retrospectively review the PET results of non-small cell lung carcinomas detected on screening chest CT in a high-risk population., Conclusion: PET findings were negative in 32% of the cases of non-small cell carcinomas that were detected on screening CT in a high-risk patient population. These tumors were small, low-grade, or both. The most common histology was bronchioloalveolar cell carcinoma. The role of PET in evaluating screening-detected indeterminate nodules in a high-risk population may be more limited than in a general population.

Background: The relation between undergoing a single computed tomography (CT) screening for lung carcinoma and the potential long-term impact on smoking status has been equivocal. Perhaps, recommendations from multiple cancer screenings may promote smoking abstinence among individuals at high risk for lung carcinoma., Methods: The current longitudinal study comprised 926 current smokers and 594 former smokers who participated in 3 annual follow-up low-dose, fast spiral chest CT scan screenings for lung carcinoma. Baseline demographic, pulmonary function, smoking history variables, and previous abnormal findings were evaluated as predictors of self-reported point prevalence smoking abstinence., Results: Among current smokers at baseline, abstinence from smoking during the 3-year follow-up was associated with older age, worse baseline pulmonary function, and abnormal CT finding the previous year requiring interim follow-up. Of participants who received abnormal screens each of the previous 3 years, 41.9% reported smoking abstinence compared with 28.0% with 2 abnormal screens, 24.2% with 1 abnormal screen, and 19.8% with no abnormal screens. Among former smokers, abstinence from smoking was associated with a longer duration of abstinence before the baseline visit., Conclusions: Smokers with abnormal CT findings from multiple CT screens were more likely to be abstinent from smoking at the 3-year follow-up. Multiple low-dose, fast spiral chest CT scan screenings for lung carcinoma may represent teachable moments and opportunities to enhance motivation for smoking abstinence. Further research is needed to continue to investigate how annual screening may enhance motivation for health behavior change.

Randomized controlled trials of smoking interventions have not been well-documented for lung cancer screening populations. In this study, we randomly assigned 171 current smokers who were undergoing low-dose fast spiral chest CT (SCTS) for lung cancer screening to receive either standard written self-help materials or a written list of Internet resources for smoking cessation. At the 1-year follow-up, more of the subjects receiving Internet-based resources reported making a stop attempt (68% versus 48%, P=0.011). However, there were no statistically significant differences in 7-day point prevalence quit rates (5% versus 10%) or advancement in motivational readiness to stop smoking (27% versus 30%), respectively, between the groups. Clearly, more investigation is warranted into how to tailor smoking interventions for cancer screening participants.

Background: Cancer screening may provide a "teachable moment" for the reduction of high-risk behaviors. The current study evaluated smoking behavior changes in current and former smokers after low-dose, fast spiral chest computed tomography scan (CT) screening for lung carcinoma., Methods: The study was comprised of 901 current smokers and 574 former smokers who participated in a low-dose, fast spiral chest CT scan screening study for lung carcinoma. Demographic, pulmonary function, screening recommendations, and smoking history variables were evaluated as predictors of self-reported point prevalence smoking abstinence 1 year after screening., Results: Of the current smokers at baseline, 14% reported smoking abstinence at follow-up. Older age and poorer lung function were associated with smoking abstinence. Ninety percent of former smokers reported smoking abstinence at a 1-year of follow-up. A longer duration of smoking abstinence at baseline was found to be predictive of abstinence in this group., Conclusions: The 14% smoking abstinence rate was higher than would be expected for spontaneous rates of smoking cessation. Therefore, screening may provide a teachable moment for smokers. Low-dose, fast spiral chest CT scan screening recommendations were not found to be associated with smoking behavior change in either group. Further research is needed to evaluate the potential avenues through which lung carcinoma screening can be used as an opportunity for providing effective nicotine interventions., (Copyright 2003 American Cancer Society.)

Purpose: To evaluate a large cohort of patients at high risk for lung cancer by using screening with low-dose spiral computed tomography (CT) of the chest., Materials and Methods: A prospective cohort study was performed with 1,520 individuals aged 50 years or older who had smoked 20 pack-years or more. Participants underwent three annual low-dose CT examinations of the chest and upper abdomen. Characteristics of pulmonary nodules and additional findings were tabulated and analyzed., Results: Two years after baseline CT scanning, 2,832 uncalcified pulmonary nodules were identified in 1,049 participants (69%). Forty cases of lung cancer were diagnosed: 26 at baseline (prevalence) CT examinations and 10 at subsequent annual (incidence) CT examinations. CT alone depicted 36 cases; sputum cytologic examination alone, two. There were two interval cancers. Cell types were as follows: squamous cell tumor, seven; adenocarcinoma or bronchioloalveolar carcinoma, 24; large cell tumor, two; non-small cell tumor, three; small cell tumor, four. The mean size of the non-small cell cancers detected at CT was 15.0 mm. The stages were as follows: IA, 22; IB, three; IIA, four; IIB, one; IIIA, five; IV, one; limited small cell tumor, four. Twenty-one (60%) of the 35 non-small cell cancers detected at CT were stage IA at diagnosis. Six hundred ninety-six additional findings of clinical importance were identified., Conclusion: CT can depict early-stage lung cancers. The rate of benign nodule detection is high.

Background: In the Mayo Lung Project Screening Trial, there were more carcinomas identified in the screened group compared with the control group. The screened group had better survival, but there was no difference in lung carcinoma mortality between the screened group and the control group. The purpose of this study was to review all available original pathology from the trial to determine whether overdiagnosis (carcinomas that do not result in the death of the patient) or misdiagnosis of lung carcinoma may explain this discrepancy., Methods: All available lung pathology slides from patients who underwent surgery at the Mayo Clinic were reviewed independently by three blinded lung pathologists. Tumors were classified according to the 1999 World Health Organization criteria. In addition, agreement among the pathologists was assessed., Results: Among 106 patients who underwent surgery at the Mayo Clinic, slides were available for review from 105 patients, including 77 slides from the screened group and 28 slides from the control group. The original diagnosis of carcinoma was confirmed in all patients. In 7 patients (6.7%), there was unanimous agreement that the lesion was preinvasive (carcinoma in situ), and these lesions all were from the screened group. In 90 patients (85.5%), there was unanimous agreement that the tumors were invasive. In 8 patients (7.8%), there was some disagreement between the observers about whether lesions were invasive or preinvasive; 7 of these 8 lesions were from the screened group. The level of agreement among pathologists for invasive carcinomas was > 94% for all comparisons, and the kappa statistic ranged from 0.67 (substantial agreement) to 0.84 (almost perfect agreement). There was good agreement among the pathologists about tumor cell type with the kappa statistic >/= 0.65., Conclusions: The histologic diagnosis of carcinoma was confirmed for all 105 slides that were reviewed. The results of this study indicate that misdiagnosis does not explain the increased numbers of carcinomas identified in the screened group. The increased numbers of in situ carcinomas in the screened group resulted in increased numbers of squamous carcinomas in the screened group compared with the control group and may have contributed to the better survival. It is possible that carcinoma in situ accounted for some instances of overdiagnosis., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10930)

Studies suggest that screening with spiral computed tomography can detect lung cancers at a smaller size and earlier stage than chest radiography can. To evaluate low-radiation-dose spiral computed tomography and sputum cytology in screening for lung cancer, we enrolled 1,520 individuals aged 50 yr or older who had smoked 20 pack-years or more in a prospective cohort study. One year after baseline scanning, 2,244 uncalcified lung nodules were identified in 1,000 participants (66%). Twenty-five cases of lung cancer were diagnosed (22 prevalence, 3 incidence). Computed tomography alone detected 23 cases; sputum cytology alone detected 2 cases. Cell types were: squamous cell, 6; adenocarcinoma or bronchioalveolar, 15; large cell, 1; small cell, 3. Twenty-two patients underwent curative surgical resection. Seven benign nodules were resected. The mean size of the non-small cell cancers detected by computed tomography was 17 mm (median, 13 mm). The postsurgical stage was IA, 13; IB, 1; IIA, 5; IIB, 1; IIIA, 2; limited, 3. Twelve (57%) of the 21 non-small cell cancers detected by computed tomography were stage IA at diagnosis. Computed tomography can detect early-stage lung cancers. The rate of benign nodule detection is high.