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Background: Relatively little is known about various aspects of low-dose CT (LDCT) scan lung cancer screening in US clinical practice, including characteristics of cases diagnosed after screening. We assessed this using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.Research Question: What were the characteristics of patients with lung cancer, including stage and survival, whose disease was diagnosed after LDCT scan screenings?Study Design and Methods: We created an LDCT scan use cohort consisting of everyone in the 5% SEER-Medicare sample with ≥ 12 months of non-health maintenance organization (HMO) Part A and B coverage while 65 to 77 years of age from 2015 through 2019. LDCT scan use and lung cancer diagnosis rates were assessed in this cohort. Additionally, we created a lung cancer cohort consisting of patients who received a diagnosis between 2015 and 2017 at 65 to 78 years of age with complete (non-HMO Part A and B) coverage the year before diagnosis. The cases cohort comprised those screened or unscreened based on undergoing screening during that period; lung cancer characteristics and survival were compared between these groups.Results: In the LDCT scan use cohort (n = 414,358), use rates increased from 0.10 (per 100 person-years) in 2015 to 1.3 in 2019. Among those with first screenings, 39.2% underwent a subsequent screen within 18 months. The 1-year cumulative lung cancer diagnosis rate after initial screenings was 2.4%. Claims for prescreen counseling were infrequent (about 10%). Of 48,891 patients in the lung cancer cohort, 1,150 (2.4%) underwent screening. Among screened patients, 52.3%, 11.0%, 20.7%, and 16.0% received diagnoses of stages I, II, III, and IV disease, respectively. Lung cancer-specific survival through 3 years was significantly greater in screened versus unscreened patients overall and for all stages except stage II; 3-year lung cancer-specific survival was 89.0% in screened patients with stage I disease.Interpretation: LDCT scan use was low but increased over time. The lung cancer yield was substantial; cases among those who underwent screening primarily were in the early stage with high survival rates. Although screening rates were unacceptably low, screening outcomes in those Medicare recipients undergoing screening were favorable. [ABSTRACT FROM AUTHOR]

Background: Incidental respiratory disease-related findings are frequently observed on low-dose CT (LDCT) lung cancer screenings. This study analyzed data from the National Lung Screening Trial (NLST) to assess the relationship between such findings and respiratory disease mortality (RDM), excluding lung cancer.Research Question: Are incidental respiratory findings on LDCT scanning associated with increased RDM?Study Design and Methods: Subjects in the NLST LDCT arm received three annual screens. Trial radiologists noted findings related to possible lung cancer, as well as respiratory-related incidental findings. Demographic characteristics, smoking history, and medical history were captured in a baseline questionnaire. Kaplan-Meier curves were used to assess cumulative RDM. Multivariate proportional hazards models were used to assess risk factors for RDM; in addition to incidental CT scan findings, variables included respiratory disease history (COPD/emphysema, and asthma), smoking history, and demographic factors (age, race, sex, and BMI).Results: Of 26,722 subjects in the NLST LDCT arm, 25,002 received the baseline screen and a subsequent LDCT screen. Overall, 59% were male, 26.5% were aged ≥ 65 years at baseline, and 10.6% reported a history of COPD/emphysema. Emphysema on LDCT scanning was reported in 30.7% of subjects at baseline and in 44.2% at any screen. Of those with emphysema on baseline LDCT scanning, 18% reported a history of COPD/emphysema. Median mortality follow-up was 10.3 years. There were 3,639 deaths, and 708 were from respiratory diseases. Among subjects with no history of COPD/emphysema, 10-year cumulative RDM ranged from 3.9% for subjects with emphysema and reticular opacities to 1.1% for those with neither condition; the corresponding range among subjects with a COPD/emphysema history was 17.3% (both) to 3.7% (neither). Emphysema on LDCT imaging was associated with a significantly elevated RDM hazard ratio (2.27; 95% CI, 1.92-2.7) in the multivariate model. Reticular opacities (including honeycombing/fibrosis/scar) also had a significantly elevated hazard ratio (1.39; 95% CI, 1.19-1.62).Interpretation: Incidental respiratory disease-related findings observed on NLST LDCT screens were frequent and associated with increased mortality from respiratory diseases. [ABSTRACT FROM AUTHOR]

Background: The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial assessed the effect of screening with prostate-specific antigen and a digital rectal examination on prostate cancer mortality. Another endpoint of interest was the burden of total metastatic disease.Methods: All men in PLCO were assessed for metastatic prostate cancer at diagnosis; men with clinical stage I/II disease were assessed for metastatic progression. The rate of total metastatic disease was defined as metastases found either at diagnosis or through progression divided by person-years (PYs) of follow-up for all men in the trial. Metastatic progression rates were computed among men with clinical stage I/II prostate cancer. Survival among men with metastases at diagnosis was compared with survival among men with metastatic progression.Results: Among 38,340 men in the intervention arm and 38,343 men in the control arm in PLCO, there were 4974 and 4699 prostate cancer cases, respectively. The rates of total metastatic disease were 4.72 and 4.83 per 10,000 PYs in the intervention and control arms, respectively (rate ratio, 0.98; 95% CI, 0.81-1.18). The rates of metastatic progression among men with clinical stage I/II prostate cancer were 43.7 and 50.5 per 10,000 PYs in the intervention and control arms, respectively (P = .30). Prostate cancer-specific 5- and 10-year survival rates were significantly worse for men with metastatic progression (24% and 19%, respectively) than men with metastases at diagnosis (40% and 26%, respectively).Conclusions: Rates of total metastatic disease and metastatic progression were similar across arms in PLCO. Survival was worse for men with metastatic progression in comparison with those with metastatic disease at diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To assess the secondary outcome of overall mortality in the randomized Prostate, Lung, Colorectal, and Ovarian cancer screening trial. Methods: In the Prostate, Lung, Colorectal, and Ovarian trial, subjects were randomized to usual care or intervention. In the intervention arm, men and women received annual chest radiographs and two sigmoidoscopy exams. Men also received annual prostate-specific antigen tests and digital rectal exams, and women also received annual CA125 tests and trans-vaginal ultrasounds. Poisson regression and Cox proportional hazards models were used to assess differences across trial arms in overall mortality and overall mortality excluding deaths from trial cancers (OMEX). Due to slight age imbalances in later trial years, age-adjusted rate ratios and hazard ratios were computed. Results: There were 76,678 men and 78,209 women randomized, with median follow-up of 17 years. In men there was a significant reduction in both overall mortality (age-adjusted rate ratio = 0.966; 95% CI: 0.943–0.989; p = 0.004) and OMEX (age-adjusted rate ratio = 0.970, 95% CI: 0.946–0.995; p = 0.02) in the intervention versus usual care arm. In women, no reduction was seen in either overall mortality (age-adjusted rate ratio = 1.002) or OMEX (age-adjusted rate ratio = 1.006). In both sexes combined, there was a significant reduction in overall mortality (age-adjusted rate ratio = 0.980; 95% CI: 0.963–0.999; p = 0.036) but not OMEX (age-adjusted rate ratio = 0.985; 95% CI: 0.965–1.004; p = 0.13). Results were similar using age-adjusted hazard ratios. Conclusion: In the Prostate, Lung, Colorectal, and Ovarian trial, there was a small but significant reduction in overall mortality in men, and in both sexes combined, and a small but significant reduction in overall mortality excluding trial cancer deaths in men. [ABSTRACT FROM AUTHOR]

Objective: To examine prostate cancer (PCa) incidence and mortality by arm in the randomized Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial. Patients and Methods: Patients aged 55–74 years at 10 screening centres were randomized between 1993 and 2001 to an intervention or usual care arm. Patients in the intervention arm received six annual prostate‐specific antigen (PSA) tests and four annual digital rectal examinations. The patients were followed for PCa incidence and for mortality via active follow‐up processes and by linkage to state cancer registries and the National Death Index. For cancers identified through active follow‐up, trial abstractors recorded the mode of diagnosis (screen‐detected, symptomatic, other). Results: A total of 38 340 patients were randomized to the intervention arm and 38 343 to a usual care arm. The median follow‐up for mortality was 16.9 (intervention) and 16.7 years (usual care). There were 333 (intervention) and 352 (usual care) PCa cancer deaths, giving rates (per 10 000 person‐years) of 5.5 and 5.9, respectively, and a rate ratio (RR) of 0.93 (95% confidence interval [CI] 0.81–1.08; P = 0.38). The RR for overall PCa incidence was 1.05 (95% CI 1.01–1.09). The RRs by Gleason category were 1.17 (95% CI 1.11–1.23) for Gleason 2–6, 1.00 (95% CI 0.93–1.07) for Gleason 7 and 0.89 (95% CI 0.80–0.99) for Gleason 8–10 disease. By mode of detection, during the trial's screening phase, 13% of intervention arm vs 27% of usual care arm cases were symptomatic; post‐screening, these percentages were 18% in each arm. Conclusion: After almost 17 years of median follow‐up, there was no significant reduction in PCa mortality in the intervention compared with the usual care arm. There was a significant increase in Gleason 2–6 disease and a significant reduction in Gleason 8–10 disease in the intervention compared with the usual care arm. [ABSTRACT FROM AUTHOR]

Background: Screening for colorectal cancer (CRC) with flexible sigmoidoscopy (FS) has been shown to reduce CRC mortality. The current study examined whether the observed mortality reduction was due primarily to the prevention of incident CRC via removal of adenomatous polyps or to the early detection of cancer and improved survival.Methods: The Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial randomized 154,900 men and women aged 55 to 74 years. Individuals underwent FS screening at baseline and at 3 or 5 years versus usual care. CRC-specific survival was analyzed using Kaplan-Meier curves and proportional hazards modeling. The authors estimated the percentage of CRC deaths averted by early detection versus primary prevention using a model that applied intervention arm survival rates to CRC cases in the usual-care arm and vice versa.Results: A total of 1008 cases of CRC in the intervention arm and 1291 cases of CRC in the usual-care arm were observed. Through 13 years of follow-up, there was no significant difference noted between the trial arms with regard to CRC-specific survival for all CRC (68% in the intervention arm vs 65% in the usual-care arm; P =.16) or proximal CRC (68% vs 62%, respectively; P = .11) cases; however, survival in distal CRC cases was found to be higher in the intervention arm compared with the usual-care arm (77% vs 66%; P<.0001). Within each arm, symptom-detected cases had significantly worse survival compared with screen-detected cases. Overall, approximately 29% to 35% of averted CRC deaths were estimated to be due to early detection and 65% to 71% were estimated to be due to primary prevention.Conclusions: CRC-specific survival was similar across arms in the PLCO trial, suggesting a limited role for early detection in preventing CRC deaths. Modeling suggested that approximately two-thirds of avoided deaths were due to primary prevention. Future CRC screening guidelines should emphasize primary prevention via the identification and removal of precursor lesions. Cancer 2017;123:4815-22. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Introduction Renal cancer incidence has increased markedly in the United States in recent decades, largely due to incidentally detected tumours from computed tomography imaging. Here, we analyze the potential for low-dose computed tomography lung cancer screening to detect renal cancer. Methods The National Lung Screening Trial randomized subjects to three annual screens with either low-dose computed tomography or chest X-ray. Eligibility criteria included 30 + pack-years, current smoking or quit within 15 years, and age 55–74. Subjects were followed for seven years. Low-dose computed tomography screening forms collected information on lung cancer and non-lung cancer abnormalities, including abnormalities below the diaphragm. A reader study was performed on a sample of National Lung Screening Trial low-dose computed tomography images assessing presence of abnormalities below the diaphragms and abnormalities suspicious for renal cancer. Results There were 26,722 and 26,732 subjects enrolled in the low-dose computed tomography and chest X-ray arms, respectively, and there were 104 and 85 renal cancer cases diagnosed, respectively (relative risk = 1.22, 95% CI: 0.9–1.5). From 75,126 low-dose computed tomography screens, there were 46 renal cancer diagnoses within one year. Abnormalities below the diaphragm rates were 39.1% in screens with renal cancer versus 4.1% in screens without (P < 0.001). Cases with abnormalities below the diaphragms had shorter median time to diagnosis than those without (71 vs. 160 days, P = 0.004). In the reader study, 64% of renal cancer cases versus 13% of non-cases had abnormalities below the diaphragms; 55% of cases and 0.8% of non-cases had a finding suspicious for renal cancer (P < 0.001). Conclusion Low-dose computed tomography screens can potentially detect renal cancers. The benefits to harms tradeoff of incidental detection of renal tumours on low-dose computed tomography is unknown. [ABSTRACT FROM AUTHOR]

BACKGROUND Two large-scale prostate cancer screening trials using prostate-specific antigen (PSA) have given conflicting results in terms of the efficacy of such screening. One of those trials, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, previously reported outcomes with 13 years of follow-up. This study presents updated findings from the PLCO trial. METHODS The PLCO trial randomized subjects from 1993 to 2001 to an intervention or control arm. Intervention-arm men received annual PSA tests for 6 years and digital rectal examinations for 4 years. This study used a linkage with the National Death Index to extend mortality follow-up to a maximum of 19 years after randomization. RESULTS Men were randomized to the intervention arm (n = 38,340) or the control arm (n = 38,343). The median follow-up time was 14.8 years (25th/75th, 12.7/16.5 years) in the intervention arm and 14.7 years (25th/75th, 12.6/16.4 years) in the control arm. There were 255 deaths from prostate cancer in the intervention arm and 244 deaths from prostate cancer in the control arm; this meant a rate ratio (RR) of 1.04 (95% confidence interval [CI], 0.87-1.24). The RR for all-cause mortality was 0.977 (95% CI, 0.950-1.004). It was estimated that 86% of the men in the control arm and 99% of the men in the intervention arm received any PSA testing during the trial, and the estimated yearly screening-phase PSA testing rates were 46% and 84%, respectively. CONCLUSIONS Extended follow-up of the PLCO trial over a median of 15 years continues to indicate no reduction in prostate cancer mortality for the intervention arm versus the control arm. Because of the high rate of control-arm PSA testing, this finding can be viewed as showing no benefit of organized screening versus opportunistic screening. Cancer 2017;123:592-599. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objectives Low-dose computed tomography lung cancer screening has been shown to reduce lung cancer mortality but has a high false-positive rate. The precision medicine approach to low-dose computed tomography screening assesses subjects’ benefits versus harms based on their personal lung cancer risk, where harms include false-positive screens and resultant invasive procedures. We assess the relationship between lung cancer risk and the rate of false-positive LDCT screens. Methods The National Lung Screening Trial randomized high-risk subjects to three annual screens with low-dose computed tomography or chest radiographs. Following the completion of National Lung Screening Trial, the Lung CT Screening Reporting and Data System (Lung-RADS) classification system was developed and retrospectively applied to National Lung Screening Trial low-dose computed tomography findings. The rate of false-positive screens (by Lung-RADS) and the resultant invasive procedures were examined as a function of lung cancer risk estimated by a model. Results Of 26,722 subjects randomized to the low-dose computed tomography arm, 26,309 received a baseline screen and were included in the analysis. The proportion with any false positive over three screening rounds increased from 12.9% to 25.9% from lowest to highest risk decile, and the proportion with an invasive procedure following a false positive also significantly increased from 0.7% to 2.0% from lowest to highest risk decile. Conclusion These findings indicate a need for personalized low-dose computed tomography lung cancer screening decision aids to accurately convey the benefits to harm trade-off. [ABSTRACT FROM AUTHOR]

BACKGROUND The National Lung Screening Trial (NLST), which compared lung cancer screening with low-dose computed tomography (LDCT) versus chest radiography (CXR), demonstrated a statistically significant mortality benefit of LDCT screening. In the current study, the authors performed a post hoc analysis to examine whether the benefit was affected by various baseline factors, including age, sex, and smoking status, and whether it differed by tumor histology. METHODS Lung cancer death rates were computed as events over person-years of observation; the mortality risk ratio (RR) was defined as the lung cancer death rate in the LDCT versus CXR trial arms. Poisson regression was used to test for interactions of sex, age (< 65 years vs ≥ 65 years), and smoking status (current vs former) with trial arm. Mortality RRs were also computed for specific lung cancer histologies. RESULTS The overall mortality RR was 0.92 in men and 0.73 in women, with a P value for interaction of .08. RRs were similar for individuals aged < 65 years versus those aged ≥ 65 years (0.82 vs 0.87), and for current versus former smokers (0.81 vs 0.91). By tumor histology, mortality RRs were 0.75 for adenocarcinoma, 0.71 for all non-small cell lung cancers except squamous, 1.23 for squamous cell carcinoma, and 0.90 for small cell carcinoma. RRs were similar for men and women for nonsquamous non-small cell lung cancers (0.71 and 0.70, respectively); women were found to have lower RRs for small cell and squamous cell carcinoma. CONCLUSIONS A benefit of LDCT did not appear to vary substantially by age or smoking status; there was weak evidence of a differential benefit by sex. A differential benefit across lung cancer histologies may exist. Cancer 2013;119:3976-3983. Published 2013. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Recently, the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial reported no mortality benefit for annual screening with CA-125 and transvaginal ultrasound (TVU). Currently ongoing is the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), which utilizes the risk of ovarian cancer algorithm (ROCA), a statistical tool that considers current and past CA125 values to determine ovarian cancer risk. In contrast, PLCO used a single cutoff for CA125, based on current levels alone. We investigated whether having had used ROCA in PLCO could have, under optimal assumptions, resulted in a significant mortality benefit by applying ROCA to PLCO CA125 screening values. A best-case scenario assumed that all cancers showing a positive screen result earlier with ROCA than under the PLCO protocol would have avoided mortality; under a stage-shift scenario, such women were assigned survival equivalent to Stage I/II screen-detected cases. Updated PLCO data show 132 intervention arm ovarian cancer deaths versus 119 in usual care (relative risk, RR = 1.11). Forty-three ovarian cancer cases, 25 fatal, would have been detected earlier with ROCA, with a median (minimum) advance time for fatal cases of 344 (147) days. Best-case and stage-shift scenarios gave 25 and 19 deaths prevented with ROCA, for RRs of 0.90 (95% CI: 0.69-1.17) and 0.95 (95% CI: 0.74-1.23), respectively. Having utilized ROCA in PLCO would not have led to a significant mortality benefit of screening. However, ROCA could still show a significant effect in other screening trials, including UKCTOCS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine patterns of repeat prostate biopsy in a cohort of men undergoing prostate cancer screening who have a negative initial biopsy. SUBJECTS AND METHODS The Prostate, Colorectal, Lung, and Ovarian (PLCO) cancer screening trial is an ongoing study the prostate component of which consists of six annual screens with measurements of prostate-specific antigen (PSA) level and a digital rectal examination (DRE). The diagnostic follow-up of positive screening results is done by the subject’s healthcare provider outside the purview of the PLCO. We analysed the experience of repeat biopsy in men in the PLCO with an initial negative biopsy. Men were divided by indication for initial biopsy into those with suspicious PSA levels and those with suspicious DRE findings. RESULTS The probability of having a repeat biopsy within 3 years of initial biopsy was 43% for 1736 men with suspicious PSA levels and 13% for 1025 men with suspicious DRE findings. Rates of third and fourth biopsy after a previous negative biopsy were similar to the initial repeat biopsy rate in PSA-positive men. Most men had a repeat biopsy only after having an additional round of screening. The PSA level and PSA velocity determined after initial biopsy were independent risk factors for a repeat biopsy, both in PSA-positive and DRE-positive men. High-grade prostatic intraepithelial neoplasia was a risk factor for repeat biopsy before any repeat PSA or DRE testing. CONCLUSION The experience of this cohort should be generally representative of patterns of care for repeat biopsy in men undergoing periodic screening. These data can provide context to the debate over optimum practices for repeat biopsy. [ABSTRACT FROM AUTHOR]

The article focuses on the prevalence of various abnormalities on chest radiographs and the risks associated with these abnormalities. About 35% of abnormalities that are not suspicious for lung cancer has been found 8% of them have outcomes that are suspicious for cancer. The most commonly noted non-cancer abnormalities are granuloma, pleural fibrosis and emphysema.

The contribution of surveillance colonoscopy, as opposed to that of initial colonoscopy examination, to prevention of colorectal cancer (CRC) is uncertain. We estimated the preventive effect of surveillance colonoscopy by applying the recently developed metric of adenoma dwell time avoided needed to prevent 1 CRC case (DTA). We followed subjects in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial who underwent colonoscopies following positive findings from sigmoidoscopies (colonoscopy cohort, n = 15,935) for CRC incidence for 10 years. The number and timing of adenomas removed during surveillance were measured in a subset (n = 3492) of patients and extrapolated to the entire cohort to estimate the total avoided adenoma dwell time. A previously determined DTA value of 612 dwell years was applied to estimate the number of CRC cases prevented by surveillance. Proportional reduction in CRC was computed as C P /(C O +C P), where C O and C P are observed and estimated prevented cases, respectively. In the colonoscopy cohort of the PLCO, 2882 subjects had advanced adenomas (AAs), 572 had 3 or more non-advanced adenomas (NAA 3+), 4496 had 1–2 non-advanced adenomas (NAA 1-2), and 7985 had no adenoma (NA). The mean number of subsequent colonoscopy examinations over 10 years were 1.80 for subjects with AAs, 1.63 for subjects with NAA 3+ , and 1.46 for subjects with NAA 1–2. Average years of avoided adenoma dwell time per subject were 4.0 for subjects with AAs, 5.5 for subjects with NAA 3+ , and 2.4 for subjects with NAA 1–2. There were 56 cases of CRC in subjects with AAs, 4 cases of CRC in subjects with NAA 3+ , and 33 cases of CRC in subjects with NAA 1–2. Estimated proportional reductions in CRC incidence were 25.0% in subjects with AAs (95% CI, 16%–34%), 34.4% in subjects with NAA 1–2 (95% CI, 25%–40%), and 30.4% overall (in subjects with AAs, NAA 3+ , or NAA 1–2 ; 95% CI, 25%–40%). Absolute CRC incidence reductions were 7.1 per 10,000 PY in subjects with AAs and 4.1 per 10,000 PY in subjects with NAA 1-2. Using the recently developed metric of DTA, we estimated that surveillance colonoscopy in the PLCO colonoscopy cohort during 10 years of follow up prevented 30% of CRC cases. Because the methodology for estimation is indirect, the true effect is uncertain. [ABSTRACT FROM AUTHOR]

Background & Aims Little is known about the change in risk conferred by family history of colorectal cancer (CRC) as a person ages. We evaluated the effect of family history on CRC incidence and mortality after 55 years of age, when the risk of early onset cancer had passed. Methods We collected data from participants in the randomized, controlled Prostate, Lung, Colorectal and Ovarian cancer screening trial of flexible sigmoidoscopy versus usual care (55–74 years old, no history of CRC), performed at 10 US centers from 1993 to 2001. A detailed family history of colorectal cancer was obtained at enrollment, and subjects were followed for CRC incidence and mortality for up to 13 years. Results Among 144,768 participants, 14,961 subjects (10.3%) reported a family of CRC. Of 2090 incident cases, 273 cases (13.1%) had a family history of CRC; among 538 deaths from CRC, 71 (13.2%) had a family history of CRC. Overall, family history of CRC was associated with an increased risk of CRC incidence (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10–1.50; P <.0001) and increased mortality (HR, 1.31; 95% CI, 1.02–1.69; P = .03). Subjects with 1 first degree relative (FDR) with CRC ( n = 238; HR, 1.23; 95% CI, 1.07–1.42) or ≥2 FDRs with CRC ( n = 35; HR, 2.04; 95% CI, 1.44–2.86) were at increased risk for incident CRC. However, among individuals with 1 FDR with CRC, there were no differences in risk based on age at diagnosis in the FDR (for FDR <60 years of age: HR, 1.27; 95% CI, 0.97–1.63; for FDR 60–70 years of age: HR, 1.33; 95% CI, 1.06–1.62; for FDR >70 years of age: HR, 1.14; 95% CI, 0.93–1.45; P trend = .59). Conclusions After 55 years of age, subjects with 1 FDR with CRC had only a modest increase in risk for CRC incidence and death; age of onset in the FDR was not significantly associated with risk. Individuals with ≥2 FDRs with CRC had continued increased risk in older age. Guidelines and clinical practice for subjects with a family history of CRC should be modified to align CRC testing to risk. ClinicalTrials.gov number, NCT00002540 . [ABSTRACT FROM AUTHOR]

Abstract: Background: The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized screening trial demonstrated no mortality effect of screening. Here we analyze prostate cancer specific survival in PLCO and its relation to screening. Methods: 76,693 men aged 55–74 were randomized to usual care (n =38,350) or intervention (n =38,343). Intervention arm men received annual prostate-specific antigen (6 years) and digital rectal exam (4 years). Men were followed for cancer diagnosis and mortality through 13 years. Medical record abstractors confirmed prostate cancer diagnoses, stage and grade. Prostate-specific survival in PLCO cases was analyzed using Kaplan–Meier analysis and proportional hazards modeling. We utilized data from the Surveillance, Epidemiology and End Results (SEER) program to compute expected survival in PLCO and compared this to observed. Results: There was no significant difference in prostate-specific survival rates between arms; 10 year survival rates were 94.7% (intervention, n =4250 cases) versus 93.5% (usual care, n =3815 cases). Within the intervention arm, cases never screened in PLCO had lower 10 year survival rates (82%) than screen detected or interval (following a negative screen) cases, both around 95.5%. The ratio of observed to expected 10 year prostate-specific death (1-survival) rates was 0.59 (95% CI: 0.51–0.68) for all PLCO cases, 0.66 (95% CI: 0.51–0.81) for Gleason 5–7 cases and 1.07 (95% CI: 0.87–1.3) for Gleason 8–10 cases. Conclusion: Prostate cancer specific survival in PLCO was comparable across arms and significantly better than expected based on nationwide population data. How much of the better survival is due to a healthy volunteer effect and to lead-time and overdiagnosis biases is not readily determinable. [Copyright &y& Elsevier]

Objective: Transrectal ultrasound guided biopsy for diagnostic workup for prostate cancer (PCa) has a substantial false negative rate. We sought to estimate PCa incidence and mortality following negative biopsy in a cohort of men undergoing prostate cancer screening.Subjects and Methods: The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial randomized participants 55-74 years to an intervention vs control arm. Intervention arm men received annual prostate-specific antigen (PSA) tests for 6 years and digital rectal exams (DRE) for 4 years. We examined the cohort of men with a positive PSA (> 4 ng/mL) or DRE screen followed within one year by a negative biopsy. PCa incidence and mortality rates from time of first negative biopsy were analyzed as a function of PSA level at diagnosis and other factors. Cumulative incidence and mortality rates accounting for competing risk were estimated. Multivariate proportional hazards regression was utilized to estimate hazard ratios (HRs) of PCa outcomes by PSA level, controlling for age and race.Results: The negative biopsy cohort included 2855 men. Median (25th/75th) age at biopsy was 65 (61/69) years; biopsies occurred between 1994 and 2006. Median (25/75th) follow-up was 13.2 (6.5/16.8) years for incidence and 16.6 (12.3/19.2) years for mortality. 740 PCa cases were diagnosed, with 33 PCa deaths. Overall 20-year cumulative PCa incidence and mortality rates were 26.4% (95% CI: 24.8-28.1) and 1.2% (95% CI: 0.9-1.7), respectively. HRs for PCa incidence and mortality increased significantly with increasing PSA.Conclusion: The mortality rate from PCa through 20 years following a negative biopsy is low. [ABSTRACT FROM AUTHOR]

Summary: The Lung Screening Study (LSS) was a pilot study designed to assess the feasibility of conducting a large scale randomized controlled trial (RCT) of low radiation dose spiral computed tomography (LDCT) versus chest X-ray (CXR) for lung cancer screening. Baseline results of LSS have been previously reported. Here, we report on the findings at the year one screen and on the final results of the LSS study. A total of 1660 subjects were randomized to the LDCT arm and 1658 to the CXR arm. Compliance with screening declined from 96% at baseline to 86% at year one in the LDCT arm and declined from 93% at baseline to 80% at year one in the CXR arm. Positivity rates for the year one screen were 25.8% for LDCT and 8.7% for CXR. Cancer yield was significantly less at year one for LDCT, 0.57%, than at baseline, 1.9%; cancer yield for CXR increased from 0.45% at baseline to 0.68% at year one. Forty lung cancers in the LDCT arm and 20 in the CXR arm were diagnosed over the study period. Stage I cancers comprised 48% of cases in the LDCT arm and 40% in the CXR arm. A total of 16 stage III–IV cancers were observed in the LDCT arm versus nine in the CXR arm. The LSS has established the feasibility of a RCT comparing annual spiral CT to chest X-ray for lung cancer screening. [Copyright &y& Elsevier]