Factors Associated With Small Aggressive Non-Small Cell Lung Cancers in the National Lung Screening Trial: A Validation Study.

BACKGROUND: A small proportion of non-small cell lung cancers (NSCLCs) have been observed to spread to distant lymph nodes (N3) or metastasize (M1) or both, while the primary tumor is small (≤3 cm, T1). These small aggressive NSCLCs (SA-NSLSC) are important as they are clinically significant, may identify unique biologic pathways, and warrant aggressive follow-up and treatment. This study identifies factors associated with SA-NSCLC and attempts to validate a previous finding that women with a family history of lung cancer are at particularly elevated risk of SA-NSCLC. METHODS: This study used a case-case design within the National Cancer Institute's National Lung Screening Trial (NLST) cohort. Case patients and "control" patients were selected based on TNM staging parameters. Case patients (n = 64) had T1 NSCLCs that were N3 or M1 or both, while "control" patients (n = 206) had T2 or T3, N0 to N2, and M0 NSCLCs. Univariate and multivariable logistic regression were used to identify factors associated with SA-NSCLC. RESULTS: In bootstrap bias-corrected multivariable logistic regression models, small aggressive adenocarcinomas were associated with a positive history of emphysema (odds ratio [OR] = 5.15, 95% confidence interval [CI] = 1.63 to 23.00) and the interaction of female sex and a positive family history of lung cancer (OR = 6.55, 95% CI = 1.06 to 50.80). CONCLUSIONS: Emphysema may play a role in early lung cancer progression. Females with a family history of lung cancer are at increased risk of having small aggressive lung adenocarcinomas. These results validate previous findings and encourage research on the role of female hormones interacting with family history and genetic factors in lung carcinogenesis and progression.

Risk of Lung Cancer Associated with COPD Phenotype Based on Quantitative Image Analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer. This study evaluates alternative measures of COPD based on spirometry and quantitative image analysis to better define a phenotype that predicts lung cancer risk. METHODS: A total of 341 lung cancer cases and 752 volunteer controls, ages 21 to 89 years, participated in a structured interview, standardized CT scan, and spirometry. Logistic regression, adjusted for age, race, gender, pack-years, and inspiratory and expiratory total lung volume, was used to estimate the odds of lung cancer associated with FEV1/FVC, percent voxels less than -950 Hounsfield units on the inspiratory scan (HUI) and percent voxels less than -856 HU on expiratory scan (HUE). RESULTS: The odds of lung cancer were increased 1.4- to 3.1-fold among those with COPD compared with those without, regardless of assessment method; however, in multivariable modeling, only percent voxels <-856 HUE as a continuous measure of air trapping [OR = 1.04; 95% confidence interval (CI), 1.03-1.06] and FEV1/FVC < 0.70 (OR = 1.71; 95% CI, 1.21-2.41) were independent predictors of lung cancer risk. Nearly 10% of lung cancer cases were negative on all objective measures of COPD. CONCLUSION: Measures of air trapping using quantitative imaging, in addition to FEV1/FVC, can identify individuals at high risk of lung cancer and should be considered as supplementary measures at the time of screening for lung cancer. IMPACT: Quantitative measures of air trapping based on imaging provide additional information for the identification of high-risk groups who might benefit the most from lung cancer screening. Cancer Epidemiol Biomarkers Prev; 25(9); 1341-7. ©2016 AACR.

Evaluation of the lung cancer risks at which to screen ever- and never-smokers: screening rules applied to the PLCO and NLST cohorts.

BACKGROUND: Lung cancer risks at which individuals should be screened with computed tomography (CT) for lung cancer are undecided. This study's objectives are to identify a risk threshold for selecting individuals for screening, to compare its efficiency with the U.S. Preventive Services Task Force (USPSTF) criteria for identifying screenees, and to determine whether never-smokers should be screened. Lung cancer risks are compared between smokers aged 55-64 and ≥ 65-80 y. METHODS AND FINDINGS: Applying the PLCO(m2012) model, a model based on 6-y lung cancer incidence, we identified the risk threshold above which National Lung Screening Trial (NLST, n = 53,452) CT arm lung cancer mortality rates were consistently lower than rates in the chest X-ray (CXR) arm. We evaluated the USPSTF and PLCO(m2012) risk criteria in intervention arm (CXR) smokers (n = 37,327) of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). The numbers of smokers selected for screening, and the sensitivities, specificities, and positive predictive values (PPVs) for identifying lung cancers were assessed. A modified model (PLCOall2014) evaluated risks in never-smokers. At PLCO(m2012) risk ≥ 0.0151, the 65th percentile of risk, the NLST CT arm mortality rates are consistently below the CXR arm's rates. The number needed to screen to prevent one lung cancer death in the 65th to 100th percentile risk group is 255 (95% CI 143 to 1,184), and in the 30th to <65th percentile risk group is 963 (95% CI 291 to -754); the number needed to screen could not be estimated in the <30th percentile risk group because of absence of lung cancer deaths. When applied to PLCO intervention arm smokers, compared to the USPSTF criteria, the PLCO(m2012) risk ≥ 0.0151 threshold selected 8.8% fewer individuals for screening (p<0.001) but identified 12.4% more lung cancers (sensitivity 80.1% [95% CI 76.8%-83.0%] versus 71.2% [95% CI 67.6%-74.6%], p<0.001), had fewer false-positives (specificity 66.2% [95% CI 65.7%-66.7%] versus 62.7% [95% CI 62.2%-63.1%], p<0.001), and had higher PPV (4.2% [95% CI 3.9%-4.6%] versus 3.4% [95% CI 3.1%-3.7%], p<0.001). In total, 26% of individuals selected for screening based on USPSTF criteria had risks below the threshold PLCO(m2012) risk ≥ 0.0151. Of PLCO former smokers with quit time >15 y, 8.5% had PLCO(m2012) risk ≥ 0.0151. None of 65,711 PLCO never-smokers had PLCO(m2012) risk ≥ 0.0151. Risks and lung cancers were significantly greater in PLCO smokers aged ≥ 65-80 y than in those aged 55-64 y. This study omitted cost-effectiveness analysis. CONCLUSIONS: The USPSTF criteria for CT screening include some low-risk individuals and exclude some high-risk individuals. Use of the PLCO(m2012) risk ≥ 0.0151 criterion can improve screening efficiency. Currently, never-smokers should not be screened. Smokers aged ≥ 65-80 y are a high-risk group who may benefit from screening. Please see later in the article for the Editors' Summary.

Interval lung cancers not detected on screening chest X-rays: How are they different?

BACKGROUND: The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial provides us an opportunity to describe interval lung cancers not detected by screening chest X-ray (CXR) compared to screen-detected cancers. METHODS: Participants were screened for lung cancer with CXR at baseline and annually for two (never smokers) or three (ever smokers) more years. Screen-detected cancers were those with a positive CXR and diagnosed within 12 months. Putative interval cancers were those with a negative CXR screen but with a diagnosis of lung cancer within 12 months. Potential interval cancers were re-reviewed to determine whether lung cancer was missed and probably present during the initial interpretation or whether the lesion was a "true interval" cancer. RESULTS: 77,445 participants were randomized to the intervention arm with 70,633 screened. Of 5227 positive screens from any screening round, 299 resulted in screen-detected lung cancers; 151 had potential interval cancers with 127 CXR available for re-review. Cancer was probably present in 45/127 (35.4%) at time of screening; 82 (64.6%) were "true interval" cancers. Compared to screen-detected cancers, true interval cancers were more common among males, persons with <12 years education and those with a history of smoking. True interval lung cancers were more often small cell, 28.1% vs. 7.4%, and less often adenocarcinoma, 25.6% vs. 56.2% (p<0.001), more advanced stage IV (30.5% vs. 16.6%, p<0.02), and less likely to be in the right upper lobe, 17.1% vs. 36.1% (p<0.02). CONCLUSION: True interval lung cancers differ from CXR-screen-detected cancers with regard to demographic variables, stage, cell type and location. ClinicalTrials.gov number: NCT00002540.

Impact of critical care medicine training programs' palliative care education and bedside tools on ICU use at the end of life.

BACKGROUND: Intensive care unit (ICU) use at the end of life is rising. Little research has focused on associations among critical care fellows' training, institutional support, and bedside tools with ICU use at the end of life. OBJECTIVE: We evaluated whether hospital and critical care medicine program interventions were associated with ICU use in the last 6 months of life for patients with chronic illness. METHODS: Our observational, retrospective study explored associations between results from a survey of critical care program directors and hospital-level Medicare data on ICU use in the last 6 months of life. Program directors evaluated quality of palliative care education in their critical care fellowships and reported on the number of bedside tools and the presence or absence of an inpatient palliative care consultation service. RESULTS: For the 89 hospitals and 71 affiliated training programs analyzed, there were statistically significant relationships between 2 of the explanatory variables-the quality of palliative care education and the number of bedside tools-in ICU use. Each level of increased educational quality (1-5 Likert scale) was associated with a 0.57-day decrease in ICU days, whereas, for each additional, evidence-based bedside tool, there was a 0.31-day decrease. The presence of an inpatient palliative care program was not a significant predictor of ICU use. CONCLUSIONS: We found that the quality of palliative care training in critical care medicine programs and the use of bedside tools were independently associated with reduced ICU use at the end of life.

Diagnostic evaluation following a positive lung screening chest radiograph in the Prostate, Lung, Colorectal, Ovarian (PLCO) Cancer Screening Trial.

Lung cancer is the major cause of cancer mortality. One of the aims of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) was to determine if annual screening chest radiographs reduce lung cancer mortality. We enrolled 154,900 individuals, aged 55-74 years; 77,445 were randomized to the intervention arm and received an annual chest radiograph for 3 or 4 years. Participants with a positive screen underwent diagnostic evaluation under guidance of their primary physician. Methods of diagnosis or exclusion of cancer, interval from screen to diagnosis, and factors predicting diagnostic testing were evaluated. One or more positive screens occurred in 17% of participants. Positive screens resulted in biopsy in 3%, with 54% positive for cancer. Biopsy likelihood was associated with a mass, smoking, age, and family history of lung cancer. Diagnostic testing stopped after a chest radiograph or computed tomography/magnetic resonance imaging in over half. After a second or subsequent positive screen, evaluation stopped after comparison to prior radiographs in over half. Of 308 screen-detected cancers, the diagnosis was established by thoracotomy/thoracoscopy in 47.7%, needle biopsy in 27.6%, bronchoscopy in 20.1% and mediastinoscopy in 2.9%. Eighty-four percent of screen-detected lung cancers were diagnosed within 6 months. Diagnostic evaluations following a positive screen were conducted in a timely fashion. Lung cancer was diagnosed by tissue biopsy or cytology in all cases. Lung cancer was excluded during evaluation of positive screening examinations by clinical or radiographic evaluation in all but 1.4% who required a tissue biopsy.

Selection criteria for lung-cancer screening.

BACKGROUND: The National Lung Screening Trial (NLST) used risk factors for lung cancer (e.g., ≥30 pack-years of smoking and <15 years since quitting) as selection criteria for lung-cancer screening. Use of an accurate model that incorporates additional risk factors to select persons for screening may identify more persons who have lung cancer or in whom lung cancer will develop. METHODS: We modified the 2011 lung-cancer risk-prediction model from our Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to ensure applicability to NLST data; risk was the probability of a diagnosis of lung cancer during the 6-year study period. We developed and validated the model (PLCO(M2012)) with data from the 80,375 persons in the PLCO control and intervention groups who had ever smoked. Discrimination (area under the receiver-operating-characteristic curve [AUC]) and calibration were assessed. In the validation data set, 14,144 of 37,332 persons (37.9%) met NLST criteria. For comparison, 14,144 highest-risk persons were considered positive (eligible for screening) according to PLCO(M2012) criteria. We compared the accuracy of PLCO(M2012) criteria with NLST criteria to detect lung cancer. Cox models were used to evaluate whether the reduction in mortality among 53,202 persons undergoing low-dose computed tomographic screening in the NLST differed according to risk. RESULTS: The AUC was 0.803 in the development data set and 0.797 in the validation data set. As compared with NLST criteria, PLCO(M2012) criteria had improved sensitivity (83.0% vs. 71.1%, P<0.001) and positive predictive value (4.0% vs. 3.4%, P=0.01), without loss of specificity (62.9% and. 62.7%, respectively; P=0.54); 41.3% fewer lung cancers were missed. The NLST screening effect did not vary according to PLCO(M2012) risk (P=0.61 for interaction). CONCLUSIONS: The use of the PLCO(M2012) model was more sensitive than the NLST criteria for lung-cancer detection.

Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up.

BACKGROUND: The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7-10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial. METHODS: A total of 76 685 men, aged 55-74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38 340 men) and control (usual care, which sometimes included opportunistic screening; 38 345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided. RESULTS: Approximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (P(interaction) = .81), pretrial PSA testing (P(interaction) = .52), and comorbidity (P(interaction) = .68). CONCLUSIONS: After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing.

Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial.

CONTEXT: The effect on mortality of screening for lung cancer with modern chest radiographs is unknown. OBJECTIVE: To evaluate the effect on mortality of screening for lung cancer using radiographs in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial that involved 154,901 participants aged 55 through 74 years, 77,445 of whom were assigned to annual screenings and 77,456 to usual care at 1 of 10 screening centers across the United States between November 1993 and July 2001. The data from a subset of eligible participants for the National Lung Screening Trial (NLST), which compared chest radiograph with spiral computed tomographic (CT) screening, were analyzed. INTERVENTION: Participants in the intervention group were offered annual posteroanterior view chest radiograph for 4 years. Diagnostic follow-up of positive screening results was determined by participants and their health care practitioners. Participants in the usual care group were offered no interventions and received their usual medical care. All diagnosed cancers, deaths, and causes of death were ascertained through the earlier of 13 years of follow-up or until December 31, 2009. MAIN OUTCOME MEASURES: Mortality from lung cancer. Secondary outcomes included lung cancer incidence, complications associated with diagnostic procedures, and all-cause mortality. RESULTS: Screening adherence was 86.6% at baseline and 79% to 84% at years 1 through 3; the rate of screening use in the usual care group was 11%. Cumulative lung cancer incidence rates through 13 years of follow-up were 20.1 per 10,000 person-years in the intervention group and 19.2 per 10,000 person-years in the usual care group (rate ratio [RR]; 1.05, 95% CI, 0.98-1.12). A total of 1213 lung cancer deaths were observed in the intervention group compared with 1230 in usual care group through 13 years (mortality RR, 0.99; 95% CI, 0.87-1.22). Stage and histology were similar between the 2 groups. The RR of mortality for the subset of participants eligible for the NLST, over the same 6-year follow-up period, was 0.94 (95% CI, 0.81-1.10). CONCLUSION: Annual screening with chest radiograph did not reduce lung cancer mortality compared with usual care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00002540.

Quantitative CT assessment of emphysema and airways in relation to lung cancer risk.

PURPOSE: To determine whether quantitative computed tomographic (CT) measurements of emphysema and airway dimensions are associated with lung cancer risk in a screening population. MATERIALS AND METHODS: Institutional review board approval and informed consent for the use of deidentified images were obtained. In this retrospective study, CT scans were analyzed from 279 participants in the CT screening arm of the National Lung Screening Trial who were diagnosed with lung cancer and 279 participants who were not diagnosed with lung cancer after a median follow-up period of 6.6 years. Quantitative CT measurements of emphysema and right upper lobe apical segmental and subsegmental airway dimensions, and multiple patient history-related variables, were compared between the two groups. Significant variables were tested in multivariate models for association with lung cancer by using multiple logistic regression. RESULTS: The emphysema index of percentage upper lung volume less than -950 HU had the strongest association with lung cancer (mean, 10.7% [standard deviation, 13.5] in patients vs 7.2% [standard deviation, 10.4] in control subjects; P < .001), but the relationship was weak (R(2) = 0.015, P < .001, c = 0.57). No CT measures of emphysema had an association with lung cancer independent of the patient medical history variables. Airway dimensions were not associated with lung cancer. CONCLUSION: Quantitative CT measurements of emphysema but not airway dimensions were only weakly associated with lung cancer, demonstrating no potential practical value for clinical risk stratification.

Lung cancer risk prediction: Prostate, Lung, Colorectal And Ovarian Cancer Screening Trial models and validation.

INTRODUCTION: Identification of individuals at high risk for lung cancer should be of value to individuals, patients, clinicians, and researchers. Existing prediction models have only modest capabilities to classify persons at risk accurately. METHODS: Prospective data from 70 962 control subjects in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) were used in models for the general population (model 1) and for a subcohort of ever-smokers (N = 38 254) (model 2). Both models included age, socioeconomic status (education), body mass index, family history of lung cancer, chronic obstructive pulmonary disease, recent chest x-ray, smoking status (never, former, or current), pack-years smoked, and smoking duration. Model 2 also included smoking quit-time (time in years since ever-smokers permanently quit smoking). External validation was performed with 44 223 PLCO intervention arm participants who completed a supplemental questionnaire and were subsequently followed. Known available risk factors were included in logistic regression models. Bootstrap optimism-corrected estimates of predictive performance were calculated (internal validation). Nonlinear relationships for age, pack-years smoked, smoking duration, and quit-time were modeled using restricted cubic splines. All reported P values are two-sided. RESULTS: During follow-up (median 9.2 years) of the control arm subjects, 1040 lung cancers occurred. During follow-up of the external validation sample (median 3.0 years), 213 lung cancers occurred. For models 1 and 2, bootstrap optimism-corrected receiver operator characteristic area under the curves were 0.857 and 0.805, and calibration slopes (model-predicted probabilities vs observed probabilities) were 0.987 and 0.979, respectively. In the external validation sample, models 1 and 2 had area under the curves of 0.841 and 0.784, respectively. These models had high discrimination in women, men, whites, and nonwhites. CONCLUSION: The PLCO lung cancer risk models demonstrate high discrimination and calibration.

Lung cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

BACKGROUND: The 5-year overall survival rate of lung cancer patients is approximately 15%. Most patients are diagnosed with advanced-stage disease and have shorter survival rates than patients with early-stage disease. Although screening for lung cancer has the potential to increase early diagnosis, it has not been shown to reduce lung cancer mortality rates. In 1993, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was initiated specifically to determine whether screening would reduce mortality rates from PLCO cancers. METHODS: A total of 77 464 participants, aged 55-74 years, were randomly assigned to the intervention arm of the PLCO Cancer Screening Trial between November 8, 1993, and July 2, 2001. Participants received a baseline chest radiograph (CXR), followed by three annual single-view CXRs at the 10 US screening centers. Cancers were classified as screen detected and nonscreen detected (interval or never screened) and according to tumor histology. The positivity rates of screen-detected cancers and positive predictive values (PPVs) were calculated. Because 51.6% of the participants were current or former smokers, logistic regression analysis was performed to control for smoking status. All statistical tests were two-sided. RESULTS: Compliance with screening decreased from 86.6% at baseline to 78.9% at the last screening. Overall positivity rates were 8.9% at baseline and 6.6%-7.1% at subsequent screenings; positivity rates increased modestly with smoking risk categories (P(trend) < .001). The PPVs for all participants were 2.0% at baseline and 1.1%, 1.5%, and 2.4% at years 1, 2, and 3, respectively; PPVs in current smokers were 5.9% at baseline and 3.3%, 4.2%, and 5.6% at years 1, 2, and 3, respectively. A total of 564 lung cancers were diagnosed, of which 306 (54%) were screen-detected cancers and 87% were non-small cell lung cancers. Among non-small cell lung cancers, 59.6% of screen-detected cancers and 33.3% of interval cancers were early (I-II) stage. CONCLUSIONS: The PLCO Cancer Screening Trial demonstrated the ability to recruit, retain, and screen a large population over multiple years at multiple centers. A higher proportion of screen-detected lung cancers were early stage, but a conclusion on the effectiveness of CXR screening must await final PLCO results, which are anticipated at the end of 2015.

Mortality results from a randomized prostate-cancer screening trial.

BACKGROUND: The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality. METHODS: From 1993 through 2001, we randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained. RESULTS: In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. CONCLUSIONS: After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups. (ClinicalTrials.gov number, NCT00002540.)

Prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian cancer screening trial: update on findings from the initial four rounds of screening in a randomized trial.

OBJECTIVE: To describe the results of the first four rounds (T0-T3) of prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial (designed to determine the value of screening in the four cancers), that for prostate cancer is evaluating whether annual screening with prostate-specific antigen (PSA) and a digital rectal examination (DRE) reduces prostate cancer-specific mortality. SUBJECTS AND METHODS: In all, 38 349 men aged 55-74 years were randomized to undergo annual screening with PSA (abnormal >4.0 ng/mL) and a DRE. The follow-up of abnormal screening results was at the discretion of subjects' physicians. PLCO staff obtained records related to diagnostic follow-up of positive screen results. RESULTS: Compliance with screening decreased slightly from 89% at baseline to 85% at T3. Both PSA positivity rates (range 7.7-8.8% at T0-T3) and DRE positivity rates (range 6.8-7.6% at T0-T3) were relatively constant over time. The positive predictive value (PPV) of a PSA level of >4.0 ng/mL decreased from 17.9% at T0 to 10.4-12.3% at T1-T3; the PPV for DRE (in the absence of a positive PSA test) was constant over time (2.9-3.6%). Cancer was diagnosed in 1902 men (4.9%). Screen-detected cancers at T0 (549) were more likely to be clinical stage III/IV (5.8%) and to have a Gleason score of 7-10 (34%) than screen-detected cancers at T1-T3 (1.5-4.2% stage III/IV and 24-27% Gleason score 7-10 among 1054 cases). CONCLUSION: The present findings on serial prostate screening are similar to those reported from other multi-round screening studies. Determining the effect of PSA screening on prostate cancer mortality awaits further follow-up.

Factors associated with human small aggressive non small cell lung cancer.

BACKGROUND: Some non-small cell lung cancers (NSCLC) progress to distant lymph nodes or metastasize while relatively small. Such small aggressive NSCLCs (SA-NSCLC) are no longer resectable with curative intent, carry a grave prognosis, and may involve unique biological pathways. This is a study of factors associated with SA-NSCLC. METHODS: A nested case-case study was embedded in the National Cancer Institute's Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. SA-NSCLC cases had stage T1, N3, and/or M1 NSCLC (n = 48) and non-SA-NSCLC cases had T2 to T3, N0 to N2, and M0 NSCLC (n = 329). Associations were assessed by multiple logistic regression. RESULTS: SA-NSCLCs were associated with younger age at diagnosis [odds ratio (OR)(>or=65 versus <65), 0.44; 95% confidence interval (95% CI), 0.22-0.88], female gender, family history of lung cancer, and the interaction gender*family history of lung cancer and were inversely associated with ibuprofen use (OR(yes versus no), 0.29; 95% CI, 0.11-0.76). The ORs for associating gender (women versus men) with SA-NSCLC in those with and without a family history of lung cancer were 11.76 (95% CI, 2.00-69.22) and 1.86 (95% CI, 0.88-3.96), respectively. These associations held adjusted for histology and time from screening to diagnosis and when alternative controls were assessed. CONCLUSION: SA-NSCLC was associated with female gender, especially in those with a family history of lung cancer. If these exploratory findings, which are subject to bias, are validated as causal, elucidation of the genetic and female factors involved may improve understanding of cancer progression and lead to preventions and therapies. Ibuprofen may inhibit lung cancer progression.

Palliative care in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition).

UNLABELLED: GOALS/OBJECTIVES: To review the scientific evidence on symptoms and specific complications that are associated with lung cancer, and the methods available to palliate those symptoms and complications. METHODS: MEDLINE literature review (through March 2006) for all studies published in the English language, including case series and case reports, since 1966 using the following medical subject heading terms: bone metastases; brain metastases; cough; dyspnea; electrocautery; hemoptysis; interventional bronchoscopy; laser; pain management; pleural effusions; spinal cord metastases; superior vena cava syndrome; and tracheoesophageal fistula. RESULTS: Pulmonary symptoms that may require palliation in patients who have lung cancer include those caused by the primary cancer itself (dyspnea, wheezing, cough, hemoptysis, chest pain), or locoregional metastases within the thorax (superior vena cava syndrome, tracheoesophageal fistula, pleural effusions, ribs, and pleura). Respiratory symptoms can also result from complications of lung cancer treatment or from comorbid conditions. Constitutional symptoms are common and require attention and care. Symptoms referable to distant extrathoracic metastases to bone, brain, spinal cord, and liver pose additional problems that require a specific response for optimal symptom control. There are excellent scientific data regarding the management of many of these issues, with lesser evidence from case series or expert opinion on other aspects of providing palliative care for lung cancer patients. CONCLUSIONS: Palliation of symptoms and complications in lung cancer patients is possible, and physicians who provide such care must be knowledgeable about these issues.

Chronic cough due to lung tumors: ACCP evidence-based clinical practice guidelines.

UNLABELLED: GOALS/OBJECTIVES: To review the scientific evidence on cough associated with tumors in the lungs. METHODS: MEDLINE literature review (through March 2004) for all studies published in the English language, including case series and case reports, since 1966 using the medical subject heading terms "cough" and "lung neoplasms." RESULTS: Primary bronchogenic carcinoma is the most common lethal neoplasm in the United States. Malignancies that arise in other organs will often metastasize to the lungs. Any form of cancer involving the lungs may be associated with cough. However, cough is far more likely to indicate involvement of the airways than the lung parenchyma because of the location of cough receptors. Cough is present in >65% of patients at the time lung cancer is diagnosed, and productive cough is present in >25% of patients. While cough as a presenting symptom of lung cancer is common, many studies have shown that lung cancer is the cause of chronic cough in