Prostate, Lung, Colorectal And Ovarian Trial Research Articles

Ultra-processed food consumption and risk of chronic respiratory diseases mortality

Chronic respiratory diseases (CRDs) are diseases of the respiratory tract and are among the most prominent causes of disability and mortality globally(1). Chronic obstructive pulmonary disease (COPD) and lung cancer are among the leading cause of death among all CRDs(2). Evidence showed that diet, particularly ultra-processed foods (UPFs) are strongly associated with cardiovascular disease, diabetes, cancer, and depression(3). However, the link between UPFs intake and CRDs has rarely been investigated. we aimed to examine the association between UPF consumption and risk of mortality due to CRDs overall, COPD and lung cancer among adults in the USA. A total of 96,607 participants aged 55 years and over were obtained from Prostate, Lung, Colorectal and Ovarian (PLCO) cancer study, a randomised trial designed to investigate the effects of screening on cancer-related mortality. However, data collected also afforded the opportunity to examine the relationships between UPF intake and mortality caused by respiratory diseases. Dietary history of participants was collected at baseline using a validated food frequency questionnaire as was the presence of respiratory diseases. Food items were grouped into one of the four NOVA food classification system(4). Cox regression was fitted to estimate the risk of all-cause mortality and cause-specific mortality due to increased consumption of UPFs over time. Competing risk regression was used to account for the competing risks events and effect of participant loss. During the follow-up period of 1,379,655.5 person-years (median 16.8 years), 28700 all-cause, 4,901 all respiratory, 2,015 lung cancer and 1,536 COPD mortalities occurred. A dose-response association was found between higher UPF intake and mortality from all respiratory diseases and COPD, but not lung cancer. After considering competing events, higher intake of UPF increased the risk of mortality from all respiratory diseases by 10% (HR: 1.10; 95% CI: 1.01, 1.21) and COPD by 20% (HR: 1.20; 95% CI: 1.02, 1.42). After imputation for missing data, the risk of lung cancer increased by 25% among participants in the highest quintile of UPF intake. The PLCO trial data highlighted that consumption of UPF increased respiratory mortality, among those with COPD, however further mechanistic studies are recommended to further clarify the link between UPF and lung cancer. This study also indicated that a high intake of UPF generally increases the risk of mortality of those with respiratory diseases and contributes to a large body of evidence indicating that higher UPF consumption increases the overall risk of mortality.

Assessing eligibility for lung cancer screening using parsimonious ensemble machine learning models: A development and validation study.

Risk-based screening for lung cancer is currently being considered in several countries; however, the optimal approach to determine eligibility remains unclear. Ensemble machine learning could support the development of highly parsimonious prediction models that maintain the performance of more complex models while maximising simplicity and generalisability, supporting the widespread adoption of personalised screening. In this work, we aimed to develop and validate ensemble machine learning models to determine eligibility for risk-based lung cancer screening. For model development, we used data from 216,714 ever-smokers recruited between 2006 and 2010 to the UK Biobank prospective cohort and 26,616 high-risk ever-smokers recruited between 2002 and 2004 to the control arm of the US National Lung Screening (NLST) randomised controlled trial. The NLST trial randomised high-risk smokers from 33 US centres with at least a 30 pack-year smoking history and fewer than 15 quit-years to annual CT or chest radiography screening for lung cancer. We externally validated our models among 49,593 participants in the chest radiography arm and all 80,659 ever-smoking participants in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial. The PLCO trial, recruiting from 1993 to 2001, analysed the impact of chest radiography or no chest radiography for lung cancer screening. We primarily validated in the PLCO chest radiography arm such that we could benchmark against comparator models developed within the PLCO control arm. Models were developed to predict the risk of 2 outcomes within 5 years from baseline: diagnosis of lung cancer and death from lung cancer. We assessed model discrimination (area under the receiver operating curve, AUC), calibration (calibration curves and expected/observed ratio), overall performance (Brier scores), and net benefit with decision curve analysis. Models predicting lung cancer death (UCL-D) and incidence (UCL-I) using 3 variables-age, smoking duration, and pack-years-achieved or exceeded parity in discrimination, overall performance, and net benefit with comparators currently in use, despite requiring only one-quarter of the predictors. In external validation in the PLCO trial, UCL-D had an AUC of 0.803 (95% CI: 0.783, 0.824) and was well calibrated with an expected/observed (E/O) ratio of 1.05 (95% CI: 0.95, 1.19). UCL-I had an AUC of 0.787 (95% CI: 0.771, 0.802), an E/O ratio of 1.0 (95% CI: 0.92, 1.07). The sensitivity of UCL-D was 85.5% and UCL-I was 83.9%, at 5-year risk thresholds of 0.68% and 1.17%, respectively, 7.9% and 6.2% higher than the USPSTF-2021 criteria at the same specificity. The main limitation of this study is that the models have not been validated outside of UK and US cohorts. We present parsimonious ensemble machine learning models to predict the risk of lung cancer in ever-smokers, demonstrating a novel approach that could simplify the implementation of risk-based lung cancer screening in multiple settings.

Single nucleotide polymorphisms in FOXP1 and RORA of the lymphocyte activation-related pathway affect survival of lung cancer patients.

BackgroundLymphocyte activation is part of a complex microenvironment that affects the development and progression of solid tumors. The present study analyzed the associations between genetic variants in lymphocyte activation-related genes and survival of patients with non-small cell lung cancer (NSCLC).MethodsOur study evaluated the associations of 14,400 (1,599 genotyped and 12,801 imputed) single-nucleotide polymorphisms (SNPs) in 176 lymphocyte activation pathway-related genes with survival of 1,185 NSCLC patients in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and validated the results in another independent dataset of 984 NSCLC patients from the Harvard Lung Cancer Susceptibility (HLCS) trial.ResultsMultivariable Cox proportional hazards regression analyses identified two distinct and possibly functional variants in forkhead box P1 (FOXP1; rs2568847 G>C) and RAR-related orphan receptor A (RORA; rs922782 T>G) that were significantly and independently associated with overall survival (OS) [adjusted hazards ratios (HRs) of 1.21 and 0.82, respectively; 95% confidence intervals (CI), 1.11 to 1.32 and 0.76 to 0.88, respectively; P=5.38×10−6 and 2.68×10−2, respectively]. Combined analysis of the unfavorable genotypes showed a significant correlation with both OS and disease-specific survival (DSS) in patients with NSCLC patients from PLCO trial (both Ptrend<0.0001). Further expression quantitative trait loci (eQTL) analysis using RORA mRNA expression and genotype data in the 1000 Genomes Project demonstrated that the RORA rs922782 G allele predicted mRNA expression levels.ConclusionsGenetic variants in FOXP1 and RORA of the lymphocyte activation pathway may be promising predictors of NSCLC survival. The RORA rs922782 G allele may predict NSCLC survival, possibly by controlling RORA mRNA expression.

Association between dietary sodium, potassium intake and lung cancer risk: evidence from the prostate, lung, colorectal and ovarian cancer screening trial and the Women's Health Initiative.

BackgroundEpidemiological studies have reported that dietary mineral intake plays an important role on lung cancer risk, but the association of sodium, potassium intake is still unclear.MethodsWe determined the association between dietary sodium, potassium intake and lung cancer risk based on the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial and the Women’s Health Initiative (WHI). Totally 165,409 participants who completed the baseline questionnaire (BQ) and diet history questionnaire (DHQ) were included into the analytical dataset, including 92,984 (44,959 men and 48,025 women) from the PLCO trial and 72,425 (women only) from the WHI cohort. Multivariable Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident lung cancer associated with dietary potassium and sodium intake. The dose-response relationship was also described using the spline smoothed curve after adjusting covariates.ResultsAfter the median follow-up of 8.55 and 18.56 years, 1,278 and 1,631 new cases of lung cancer were identified in the PLCO trial and WHI cohort, respectively. Intake of sodium was significantly associated with the incidence of lung cancer in the PLCO trial after multivariate adjustment for men (HR: 1.19, 95% CI: 1.05–1.35; P for linear trend =0.044). There was a suggestion that lung cancer risk had a quadratic curve correlation with the increase of potassium intake for women (third vs. lowest quintile: HR: 0.72, 95% CI: 0.54–0.96; P for quadratic trend =0.042). The similar results showing an inverse association between potassium intake and lung cancer risk were also observed in the WHI cohort for women (highest vs. lowest quintile: HR: 0.82, 95% CI: 0.70–0.97; P for linear trend =0.009).ConclusionsAppropriate intake of potassium has a protective effect against lung cancer, while high consumption of sodium is associated with an increased risk of lung cancer.

Other and All-Cause Mortality among Men Diagnosed with Prostate Cancer in the PLCO Trial

Men with prostate cancer have high cause-specific survival, and most deaths are from other causes. This study aimed to investigate other and all-cause mortality in a large cancer screening cohort. From the PLCO (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial cohort, we selected men diagnosed with prostate cancer from 1994-2014. We examined other and all-cause survival by prostate cancer risk level, defined as the D'Amico categories for localized disease (low, intermediate and high risk) plus nonlocalized disease. We developed 3 Cox proportional hazards models to assess the relationship between risk level and survival. Model I controlled for age, race, study arm and diagnosis year. Model II additionally controlled for other demographic and medical history factors. Model III additionally controlled for initial treatment. Of 76,672 men in PLCO and 10,859 prostate cancer cases, 9,248 (85.2%) had known prostate cancer risk level (mean±SD age 70.4±6.2 years). Median followup time from diagnosis was 10.8 years (IQR 6.8-15.0). Of 3,318 deaths 81% were from other causes. Compared to the low risk group, other-cause mortality HRs were 1.13 (95% CI 1.04-1.23), 1.35 (95% CI 1.21-1.50) and 1.63 (95% CI 1.35-1.97) for intermediate risk, high risk and advanced disease, respectively, in model II. Model III HRs were similar to model II except for advanced disease, where the HR decreased to 1.35. Other-cause survival was greater in lower vs higher risk disease, even after controlling for lifestyle characteristics and comorbidities. Further research is needed to identify factors contributing to this higher other-cause mortality to help mitigate the risk.

Overall and Multiphasic Findings of the Prostate, Lung, Colorectal and Ovarian (PLCO) Randomized Cancer Screening Trial.

Screening tests are typically evaluated for a single disease, but multiple tests for multiple diseases are performed in practice. The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial assessed testing for four cancers simultaneously and can be viewed as a multiphasic cancer intervention. This paper presents overall and multiphasic findings of this trial. The PLCO trial was a randomized multi-center trial conducted at ten screening centers in the US. Participants were 76,682 men and 78,215 women ages 55 - 74 and free of the target cancers at trial entry. Screening tests were PSA and digital rectal examination for prostate cancer, chest x-ray for lung cancer, flexible sigmoidoscopy for colorectal cancer, CA125 and transvaginal ultrasound for ovarian cancer. Outcomes and harms of screening were assessed including compliance, test results, incidence, mortality, false positives and overdiagnosis. Screening compliance was 82%, 72,820 (8%) of 906,064 exams were positive, the overall PPV was 4.2% and the cancer detection rate was 3.38/1000. A mortality reduction was observed only for colorectal cancer (RR 0.72, 95% CI 0.61 - 0.85) with no effect on all-cause mortality. Ninety-six percent of positive exams were falsely positive and there was a suggestion of overdiagnosis of prostate and possibly ovarian cancers. Multiphasic testing resulted in 7374 men and 2748 women experiencing multiple false positive results from multiple types of tests. Multiphasic cancer screening led to reduced mortality for one target cancer and imposed a burden on the health care system that included substantial false positives and likely overdiagnosis.

Ovarian cancer screening-ultrasound; impact on ovarian cancer mortality.

Although ovarian cancer (OC) is the most lethal of all female malignancies, debate still exists concerning the benefits and harms of the screening programs and their impact on long-term survival and mortality from the disease. The most widely tested screening strategies have focused on transvaginal ultrasound (TVU) and on algorithms that measure serum levels or interval changes of cancer antigen-125 (CA-125) either individually or in combination. Transvaginal ultrasound can identify size and morphology changes of the ovary that may signal a developing malignancy; yet, it is still accused of having a low specificity. There is preliminary evidence that screening can improve survival, but the impact of screening on mortality from OC is still unclear and warrants further validation. In spite of having many published prospective studies, up to-date, none have been able to demonstrate conclusively a reduction in mortality from OC both in the screened general or high-risk population. Data from the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial has not shown survival or mortality benefits in the general population. Most prospective trials have reported a decrease in stage at detection (with the exception of the PLCO trial), thereby allowing treatment to be initiated when the disease is most curable. Research is in progress to develop new diagnostic tests and novel biomarkers, which when used in combination can increase the accuracy and outcomes of screening. In this review article, we will discuss the debate provoked on OC screening programs and the impact of using ultrasound on the reduction of OC-related mortality.

Concentrated sugars and incidence of prostate cancer in a prospective cohort.

The association between consumption of added or concentrated sugars and prostate cancer risk is unclear. We examined the association between concentrated sugars in beverages and desserts and prostate cancer risk among 22 720 men in the usual-care arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, enrolled during 1993-2001. After a median follow-up of 9 years, 1996 men were diagnosed with prostate cancer. Cox proportional hazards regression models were used to estimate hazard ratios (HR) for prostate cancer risk and 95 % CI, adjusting for potential confounding factors. Increased consumption of sugars from sugar-sweetened beverages was associated with increased risk of prostate cancer for men in the highest quartile of sugar consumption (HR: 1·21; 95 % CI 1·06, 1·39), and there was a linear trend (P<0·01). There were no linear associations between prostate cancer risk and consumption of sugars from fruit juices or dessert foods. In conclusion, in this prospective substudy within the PLCO trial, consumption of sugars from sugar-sweetened beverages was associated with increased risk of prostate cancer among men receiving standard medical care. Our study suggests that limiting intake of sugars from beverages may be important in the prevention of prostate cancer.

Number of Adenomas Removed and Colorectal Cancers Prevented in Randomized Trials of Flexible Sigmoidoscopy Screening

Screening for colorectal cancer (CRC) with sigmoidoscopy reduces CRC incidence by detecting and removing adenomas. The number needed to screen is a measure of screening efficiency, but is not directly associated with adenoma removal. We propose the following 2 new metrics for quantifying the relationship between adenoma removal and CRC prevented: number of adenomas needed to remove (NNR) and adenoma dwell time avoided (DTA). We collected data from 4 randomized trials of sigmoidoscopy screening (1 in the United States and 3 in Europe) to assess NNR and DTA. For each trial, NNR was computed as the number of adenomas removed from subjects in the intervention group, divided by the number of CRCs prevented. DTA was computed similarly but taking into account the timing of adenoma removal. Combined results across trials were assessed using standard meta-analytic techniques. The estimated NNR for the PLCO (Prostate, Lung, Colorectal and Ovarian) trial was 74 (95% confidence interval [CI], 56-110), for the NORCCAP (Norwegian Colorectal Cancer Prevention) trial was 71 (95% CI, 44-174), for the SCORE (Screening for Colon Rectum) trial was 27 (95% CI, 14-135), and for the UKFSST (UK Flexible Sigmoidoscopy Screening Trial) was 36 (95% CI, 28-52). The combined estimate (meta-analysis) of NNR was 52 (95% CI, 36-93) assuming heterogeneity (P for heterogeneity= .014). DTA estimates among trials ranged from 278 to 730 years, with a combined estimate of 500 (95% CI, 344-833) years assuming heterogeneity (P for heterogeneity= .035), or 2 CRC cases prevented per 1000 adenoma dwell years avoided. The combined estimates of NNR and DTA restricted to advanced adenomas were 13 (95% CI, 9-22) and 122 (95% CI, 90-190) years, respectively. We collected data from 4 randomized trials of sigmoidoscopy screening for CRC to develop metrics of endoscopic efficiency, NNR and DTA, which are directly linked to adenoma detection and removal. They can be used to compare screening among endoscopic modalities and to more precisely measure adenoma to carcinoma transition rates.

Vasectomy and Risk of Prostate Cancer in a Screening Trial.

Background: Vasectomy has been implicated as a risk factor for prostate cancer in multiple epidemiologic studies over the past 25 years. Whether this relationship is causal remains unclear. This study examines the association between vasectomy and prostate cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which randomized men to usual care or annual prostate cancer screening.Methods: We performed a retrospective analysis of 13-year screening and outcomes data from the PLCO trial. Multivariable Cox proportional hazards regression stratified by study arm and age at vasectomy was performed.Results: There was an increased risk of prostate cancer in men who had undergone a vasectomy and were randomized to the usual care arm of the study (adjusted HR, 1.11; 95% confidence interval, 1.03-1.20; P = 0.008). There was no association between vasectomy and diagnosis of prostate cancer in men randomized to the prostate cancer screening arm. Only men undergoing vasectomy at an older age in the usual care arm of the study, but not the prostate cancer screening arm, were at increased risk of being diagnosed with prostate cancer.Conclusions: Vasectomy was not associated with prostate cancer risk among men who were screened for prostate cancer as part of a clinical trial, but was associated with prostate cancer detection in men receiving usual care.Impact: The positive association between vasectomy and prostate cancer is likely related to increased detection of prostate cancer based on patterns of care rather than a biological effect of vasectomy on prostate cancer development. Cancer Epidemiol Biomarkers Prev; 26(11); 1653-9. ©2017 AACR.

Extended mortality results for ovarian cancer screening in the PLCO trial with median 15 years follow-up

BackgroundThe Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial originally reported no mortality benefit of ovarian cancer screening after a median of 12.4years of follow-up. The UKCTOCS screening trial failed to show a statistically significant mortality reduction in the primary analysis but reported an apparent increased mortality benefit in trial years 7–14 compared to 0–7. Here we report an updated analysis of PLCO with extended mortality follow-up. MethodsParticipants were randomized from 1993 to 2001 at ten U.S. centers to an intervention or usual care arm. Intervention arm women were screened for ovarian cancer with annual trans-vaginal ultrasound (TVU) (4years) and CA-125 (6years), with a fixed cutoff at 35U/mL for CA-125. The original follow-up period was for up to 13years (median follow-up 12.4years); in this analysis follow-up for mortality was extended by up to 6years. Results39,105 (intervention) and 39,111 (usual care) women were randomized, of which 34,253 and 34,304, respectively, had at least one ovary at baseline. Median follow-up was 14.7years in each arm and maximum follow-up 19.2years in each arm. A total of 187 (intervention) and 176 (usual care) deaths from ovarian cancer were observed, for a risk-ratio of 1.06 (95% CI: 0.87–1.30). Risk-ratios were similar for study years 0–7 (RR=1.04), 7–14 (RR=1.06) and 14+ (RR=1.09). The risk ratio for all-cause mortality was 1.01 (95% CI: 0.97–1.05). Ovarian cancer specific survival was not significantly different across trial arms (p=0.16). ConclusionExtended follow-up of PLCO indicated no mortality benefit from screening for ovarian cancer with CA-125 and TVU.

A System Dynamics Model of Serum Prostate-Specific Antigen Screening for Prostate Cancer.

Since 2012, US guidelines have recommended against prostate-specific antigen (PSA) screening for prostate cancer. However, evidence of screening benefit from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial and the European Randomized Study of Screening for Prostate Cancer has been inconsistent, due partly to differences in noncompliance and contamination. Using system dynamics modeling, we replicated the PLCO trial and extrapolated follow-up to 20 years. We then simulated 3 scenarios correcting for contamination in the PLCO control arm using Surveillance, Epidemiology, and End Results (SEER) incidence and survival data collected prior to the PSA screening era (scenario 1), SEER data collected during the PLCO trial period (1993-2001) (scenario 2), and data from the European trial's control arm (1991-2005) (scenario 3). In all scenarios, noncompliance was corrected using incidence and survival rates for men with screen-detected cancer in the PLCO screening arm. Scenarios 1 and 3 showed a benefit of PSA screening, with relative risks of 0.62 (95% confidence interval: 0.53, 0.72) and 0.70 (95% confidence interval: 0.59, 0.83) for cancer-specific mortality after 20 years, respectively. In scenario 2, however, there was no benefit of screening. This simulation showed that after correcting for noncompliance and contamination, there is potential benefit of PSA screening in reducing prostate cancer mortality. It also demonstrates the utility of system dynamics modeling for synthesizing epidemiologic evidence to inform public policy.

Prostate genetic score (PGS-33) is independently associated with risk of prostate cancer in the PLCO trial.

To investigate the ability of the prostate genetic score (PGS-33), a germ-line biomarker of prostate cancer (PCa) risk, to categorize men participating in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We obtained the genetic data from the Cancer Genetic Markers of Susceptibility (CGEMS), a nested case control study examining germ-line DNA in the screened arm of the PLCO trial. A PGS-33 was calculated based on their genotype at 33 PCa associated single nucleotide polymorphisms (SNPs). The primary outcome was the diagnosis of PCa and primary predictor was PGS-33. We identified 2,244 subjects (no cancer, N = 1017) and cases (N = 1227). The PGS-33 (P<0.001), prostate specific antigen (PSA; P < 0.001), family history of PCa (< 0.001), abnormal digital rectal exam (DRE, P < 0.001), and history of ever smoking (P = 0.037) were associated with a PCa diagnosis. In multivariable analysis, the log (PGS-33) was associated with PCa diagnosis with an odds ratio of 1.68 (95% CI 1.36-2.08, P < 0.001), log (PSA) (OR 8.2; 95% CI 6.75-10.04, P < 0.001), and family history of PCa (OR 2.01; 95% CI 1.26-3.20, P = 0.003). PGS-33 quartiles noted an increasing rate of PCa detection in addition to PSA: 43.2% (Q1), 47.8% (Q2), 58.8% (Q3), and 69.4 (Q4) (P < 0.001) and improvement in PSA performance (P < 0.001). Germ-line DNA in the form of the PGS-33 is able to risk stratify men regarding their risk of PCa. The PGS-33 may have implications regarding who may benefit most from PCa screening and possibly add to PSA performance.

Telomere length in white blood cell DNA and lung cancer: a pooled analysis of three prospective cohorts.

We investigated the relationship between telomere length and lung cancer in a pooled analysis from three prospective cohort studies: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, conducted among men and women in the United States, and previously published data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial conducted among male smokers in Finland, and the Shanghai Women's Health Study (SWHS), which is comprised primarily of never-smokers. The pooled population included 847 cases and 847 controls matched by study, age, and sex. Leukocyte telomere length was measured by a monochrome multiplex qPCR assay. We used conditional logistic regression models to calculate ORs and their 95% confidence intervals (CI) for the association between telomere length and lung cancer risk, adjusted for age and pack-years of smoking. Longer telomere length was associated with increased lung cancer risk in the pooled analysis [OR (95% CI) by quartile: 1.00; 1.24 (0.90-1.71); 1.27 (0.91-1.78); and 1.86 (1.33-2.62); P trend = 0.000022]. Findings were consistent across the three cohorts and strongest for subjects with very long telomere length, i.e., lung cancer risks for telomere length [OR (95% CI)] in the upper half of the fourth quartile were 2.41 (1.28-4.52), 2.16 (1.11-4.23), and 3.02(1.39-6.58) for the PLCO trial, the ATBC trial, and the SWHS, respectively. In addition, the association persisted among cases diagnosed more than 6 years after blood collection and was particularly evident for female adenocarcinoma cases. Telomere length in white blood cell DNA may be a biomarker of future increased risk of lung cancer in diverse populations.

Powering cancer screening for overall mortality.

Powering cancer screening for overall mortality.

Association of obesity with cardiovascular disease mortality in the PLCO trial

ObjectiveObesity is a risk factor for cardiovascular disease (CVD) mortality, but the association between obesity and specific causes of CVD mortality is still under investigation. MethodWe prospectively examined body-mass index (BMI) in relation to CVD-specific causes of death in approximately 86,000 US men and women in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, followed for up to 13years. BMI was calculated from self-reported weight and height at baseline. Hazard ratios (HRs) were calculated overall and stratified by sex, smoking status, and educational level. ResultOverweight non-obese participants (BMI: 25.0–29.9) were not at excess risk for CVD mortality (HR and CIs are 1.02 [0.92–1.13]), compared to participants of normal BMI (18.5–24.9). Excess CVD mortality was observed for participants of BMI 30.0–34.9 (HR and CIs: 1.29 [1.13–1.48]), BMI 35.0–39.9 (HR and CIs: 1.87 [1.51–2.32]) and BMI 40.0+ (HR and CIs: 2.21 [1.57–3.21]) (p<0.001 for trend). BMI was unrelated to mortality due to stroke. The observed association of BMI with CVD was independent of gender, smoking status and educational level. ConclusionObesity is associated with increased mortality due to CVD.

Abstract 150: Ovarian visualization in transvaginal ultrasound scans and risk of ovarian cancer.

Abstract Background. Ovarian cancer is typically diagnosed at an advanced stage, resulting in poor survival. Detection of ovarian cancer at an early curable stage could reduce mortality; however, annual screening with transvaginal ultrasound (TVU) and CA-125 serum levels using predetermined cutpoints did not lower mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) trial. In this trial, approximately 40% of TVU scans resulted in non-visualization of the ovaries. Currently, TVU studies consider non-visualization of the ovaries as having normal ovaries, even though this may confer risk information. Accordingly, we assessed risk of ovarian cancer among women with non-visualization of the ovaries by TVU in the PLCO trial. Methods. Study participants were women from the ovarian screening arm of the PLCO trial. Briefly, women aged 55-74 years were recruited at ten US clinical centers between 1993 and 2001. Those with a previous diagnosis of ovarian cancer were excluded from enrollment. Subjects with at least one ovary underwent a TVU at baseline and annually for 3 additional years and were followed-up for up to 13 years. Individuals were excluded from the current analysis if they did not complete the baseline questionnaire or did not have at least one adequate screening (i.e., visualization of the iliac vessels). Ovaries were considered not visualized if they were not seen after a search of at least 5 minutes. Associations between participant characteristics and ovarian visualization were estimated using logistic regression models adjusted for age and calendar year. Hazard ratios (HR) and 95% confidence intervals (CI) were computed to estimate the risk of ovarian cancer with TVU visualization using Cox proportional hazard models. Age was the time metric and models were adjusted for calendar year, body mass index (BMI), race, parity and oral contraceptive (OC) use. Results. Our analysis included 29,329 women, with 98.6% of them having two or more TVUs. Two hundred and five women were diagnosed with invasive ovarian cancer during follow-up. Lack of visualization of the ovaries by TVU was associated with older age, non-White race, greater BMI, ever use of OC and ever having children. However, ovarian visualization was not associated with risk of ovarian cancer (HR=1.17; 95% CI: 0.86-1.59). Moreover, women with visualized ovaries but negative TVUs were not at elevated ovarian cancer risk compared to women with non-visualized ovaries (HR=1.06; 95% CI: 0.77-1.45). Conclusions. Women with non-visualization of the ovaries by TVU and those with visualization and a negative result do not have a different risk of ovarian cancer, suggesting that data for these women may be combined. Ongoing analysis will examine serial measurements of ovarian volume by TVU and ovarian cancer risk. Citation Format: Clara Bodelon, Amanda Black, Ruth M. Pfeiffer, Mark E. Sherman. Ovarian visualization in transvaginal ultrasound scans and risk of ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 150. doi:10.1158/1538-7445.AM2013-150

Longitudinal Screening Algorithm That Incorporates Change Over Time in CA125 Levels Identifies Ovarian Cancer Earlier Than a Single-Threshold Rule

Longitudinal algorithms incorporate change over time in biomarker levels to individualize screening decision rules. Compared with a single-threshold (ST) rule, smaller deviations from baseline biomarker levels are required to signal disease. We demonstrated improvement in ovarian cancer early detection by using a longitudinal algorithm to monitor annual CA125 levels. We retrospectively evaluated serial preclinical serum CA125 values measured annually in 44 incident ovarian cancer cases identified from participants in the PLCO (Prostate Lung Colorectal and Ovarian) Cancer Screening Trial to determine how frequently and to what extent the parametric empirical Bayes (PEB) longitudinal screening algorithm identifies ovarian cancer earlier than an ST rule. The PEB algorithm detected ovarian cancer earlier than an ST rule in a substantial proportion of cases. At 99% specificity, which corresponded to the ST-rule CA125 cutoff ≥ 35 U/mL that was used in the PLCO trial, 20% of cases were identified earlier by using the PEB algorithm. Among these cases, the PEB signaled abnormal CA125 values, on average, 10 months earlier and at a CA125 concentration 42% lower (20 U/mL) than the ST-rule cutoff. The proportion of cases detected earlier by the PEB algorithm and the earliness of detection increased as the specificity of the screening rule was reduced. The PEB longitudinal algorithm identifies ovarian cancer earlier and at lower biomarker concentrations than an ST screening algorithm adjusted to the same specificity. Longitudinal biomarker assessment by using the PEB algorithm may have application for screening other solid tumors in which biomarkers are available.

Screening for Familial Ovarian Cancer: A Ray of Hope and a Light to Steer by

Screening for Familial Ovarian Cancer: A Ray of Hope and a Light to Steer by

854 SCREENING HISTORY OF MEN WITH FATAL PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced III1 Apr 2010854 SCREENING HISTORY OF MEN WITH FATAL PROSTATE CANCER Joshua J. Meeks, Stacy Loeb, Ronald Kim, Donghui Kan, Jessica A. Banks, Phillip R. Cooper, Brian T. Helfand, and William J. Catalona Joshua J. MeeksJoshua J. Meeks Chicago, IL More articles by this author , Stacy LoebStacy Loeb Baltimore, MD More articles by this author , Ronald KimRonald Kim Chicago, IL More articles by this author , Donghui KanDonghui Kan Chicago, IL More articles by this author , Jessica A. BanksJessica A. Banks Chicago, IL More articles by this author , Phillip R. CooperPhillip R. Cooper Chicago, IL More articles by this author , Brian T. HelfandBrian T. Helfand Chicago, IL More articles by this author , and William J. CatalonaWilliam J. Catalona Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1610AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated that PSA screening was associated with a significant mortality benefit; whereas, the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial did not find a difference in mortality. Possible reasons for this discrepancy include high rates of contamination and pre-screening as well as considerable delays in the follow-up of abnormal screening test results in the PLCO trial. The objective of our study was to compare the screening history between men with prostate cancer from a large follow-up study who died from the disease to those with no evidence of disease progression after at least 7 years of follow-up. METHODS Men diagnosed with prostate cancer in a large screening program were enrolled into a prospective follow-up study. From this population, we identified 134 men who died from prostate cancer, as confirmed using the National Death Index. As a comparison group, we identified 1033 prostate cancer cases with at least 7 years of follow-up and no disease recurrence. RESULTS As shown in Table 1, men who died from prostate cancer were significantly older and had significantly higher PSA levels at diagnosis. A greater proportion of men who died from prostate cancer had a suspicious DRE and a Gleason score of 7 to 10. Although less frequent, there were some prostate cancer deaths among men diagnosed with Gleason ≤6 prostate cancer in the screening study. Overall, men who died from prostate cancer had significantly fewer PSA tests and DREs prior to the diagnosis of prostate cancer, and had a significantly greater delay between abnormal screening results and follow-up biopsy. Death from Prostate Cancer (N=134) No Recurrence with At Least 7-year Follow-up (N=1033) p-value Median Age at Diagnosis (yrs) 70 (51-85) 65 (45-79) <0.0001 Median PSA (ng/mL) 6.5 (0.3-3373) 5.4 (0-82) <0.0001 No. of PSA Screenings Mean 4.0, Median 1.0 (1-23) Mean 5.4, Median 3.0 (1-22) 0.003 # DRE Mean 2.2, Median 1.0 (0-13) Mean 3.0, Median 2.0 (0-18) 0.0005 Last DRE Suspicious (%) 73/126 (58%) 283/953 (30%) <0.0001 Biopsy Gleason ≤6 51/104 (50%) 731/818 (89%) <0.0001 Days from abnormal screening test to 1st biopsy Mean 140, Median 40 (8-1532) (N=119) Mean 181, Median 42 (1-2885) (N=890) 0.26 CONCLUSIONS In this case-case analysis of men who died from prostate cancer compared to those who did not, disease-specific death was associated with a lower frequency of PSA and DRE testing. Men who died from prostate cancer also had a significantly greater delay in undergoing biopsy following abnormal test results, suggesting that this may be an important factor behind the negative findings of the PLCO trial. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e333 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua J. Meeks Chicago, IL More articles by this author Stacy Loeb Baltimore, MD More articles by this author Ronald Kim Chicago, IL More articles by this author Donghui Kan Chicago, IL More articles by this author Jessica A. Banks Chicago, IL More articles by this author Phillip R. Cooper Chicago, IL More articles by this author Brian T. Helfand Chicago, IL More articles by this author William J. Catalona Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...