Randomization to screening for prostate, lung, colorectal and ovarian cancers and thyroid cancer incidence in two large cancer screening trials.
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ABSTRACT:
SUBMITTER: O'Grady TJ
PROVIDER: S-EPMC4156403 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:ObjectiveTo examine prostate cancer (PCa) incidence and mortality by arm in the randomized Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial.Patients and methodsPatients 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).ResultsA 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.ConclusionAfter 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.
| S-EPMC6450783 | biostudies-literature
Project description:BackgroundThe evidence of dietary carrot/carotene intake's effect on the association with colorectal cancer (CRC) risk is conflicted. We sought to examine the association of carrot/carotene intake with CRC incidence and mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening cohort.MethodsIn all, 101,680 participants were enrolled between November 1993 and July 2001 from the PLCO cohort. We employed the multivariable Cox regression analyses to estimate the hazard ratios and 95% confidence interval. Subgroup analyses and interaction tests were performed to examine the potential effect modifiers. We further applied the generalized additive model to explore the non-linear trend of the exposure to cancer-related outcomes.ResultsA total of 1,100 CRC cases and 443 cancer-related deaths were documented. We noted that the 4th quintile of dietary carrot intakes was associated with a 21% lower risk of CRC incidence, compared with the lowest quintile group (full-adjusted HRquintile4vs.quintile1 = 0.79, 95%CI = 0.65-0.97, p for trend = 0.05), while the adjusted-HR was 0.95 (95%CI = 0.89-1.02) with per SD increment of carrot intakes, and no statistically significant associations were detected between dietary α-, and β-carotene intake and CRC incidence. There were no statistically significant associations observed between carrot/carotene intakes and CRC mortality. Furthermore, there were no non-linear dose-response relationships between dietary carrot, α-, and β-carotene intake and CRC incidence and mortality (all p nonlinearity > 0.05). Of note, smoking status as a modifier on the association of dietary carrot intakes with CRC incidence but not mortality was observed.ConclusionsIn summary, this large U.S. prospective cohort study indicated that a moderate consumption of carrots was associated with a lower CRC incidence, which suggested that a certain dose-range of carrots consumed might contribute to a potential cancer-prevention effect, not the more the better.
| S-EPMC9247642 | biostudies-literature
Project description:BackgroundThe 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.Methods76,693 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.ResultsThere 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.ConclusionProstate 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.
| S-EPMC3582194 | biostudies-literature
Project description:BackgroundThe 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.MethodsA 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.ResultsCompliance 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.ConclusionsThe 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.
| S-EPMC2873186 | biostudies-literature
Project description:ImportanceMany studies have evaluated the long-term benefits of aspirin use; however, the association of aspirin use with cancer incidence and survival in older individuals remains uncertain. Additional population-based evidence of this association is necessary to better understand any possible protective effects of aspirin in older adults.ObjectiveTo investigate the association of aspirin use with risk of developing new cancers and site-specific cancer-associated survival in bladder, breast, esophageal, gastric, pancreatic, and uterine cancers.Design, setting, and participantsThis cohort study used data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Participants were aged 65 years or older at baseline (1993-2001) or reached age 65 during follow-up. Data analysis was conducted from January to June 2020.Main outcomes and measuresIncidence of and survival from the investigated cancer types. Univariable and multivariable hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression modeling, adjusting for covariates. Multivariable models for incidence included time-varying covariates.ResultsA total of 139 896 individuals (mean [SD] age at baseline, 66.4 [2.4] years; 71 884 [51.4%] women; 123 824 [88.5%] non-Hispanic White individuals) were included in the analysis. During the study period, 32 580 incident cancers (1751 [5.4%] bladder, 4552 [14.0%] breast, 332 [1.0%] esophageal, 397 [1.2%] gastric, 878 [2.7%] pancreatic, and 716 [2.2%] uterine cancers) were reported. Aspirin use was not associated with incidence of any of the investigated cancer types among individuals aged 65 years or older. Multivariable regression analysis demonstrated that aspirin use at least 3 times/week was associated with increased survival among patients with bladder (HR, 0.67; 95% CI, 0.51-0.88) and breast (HR, 0.75; 95% CI, 0.59-0.96) cancers but not among those with esophageal, gastric, pancreatic, or uterine cancer. A similar association of any aspirin use with bladder (HR, 0.75; 95% CI, 0.58-0.98) and breast (HR, 0.79; 95% CI, 0.63-0.99) cancer survival was observed.Conclusions and relevanceIn the current study, any aspirin use and aspirin use at least 3 times/week was associated with improved bladder and breast cancer survival. Associations between aspirin use and incidence of any of the investigated cancers or between aspirin use and esophageal, gastric, pancreatic, or uterine cancer survival were not observed.
| S-EPMC7811183 | biostudies-literature
Project description:BackgroundTwo recent metabolomic analyses found serum lipid, energy, and other metabolites related to aggressive prostate cancer risk up to 20 years prior to diagnosis.MethodsWe conducted a serum metabolomic investigation of prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that included annual serum total prostate-specific antigen measurement and digital rectal examination. This nested study included 380 cases diagnosed post-screening and 380 controls individually matched to cases on age, race, study centre, and blood-collection date (median time to diagnosis, 10 years (range 4.4-17 years)). Sera were analysed on a high-resolution accurate mass platform of ultrahigh-performance liquid and gas chromatography/mass spectroscopy that identified 695 known metabolites. Logistic regression conditioned on the matching factors estimated odds ratios (OR) and 95% confidence intervals of risk associated with an 80th percentile increase in the log-metabolite signal.ResultsTwenty-seven metabolites were associated with prostate cancer at P<0.05. Pyroglutamine, gamma-glutamylphenylalanine, phenylpyruvate, N-acetylcitrulline, and stearoylcarnitine showed the strongest metabolite-risk signals (ORs=0.53, 0.51, 0.46, 0.58, and 1.74, respectively; 0.001?P?0.006). Findings were similar for aggressive disease (peptide chemical class, P=0.03). None of the P-values were below the threshold of Bonferroni correction, however.ConclusionsA unique metabolomic profile associated with post-screening prostate cancer is identified that differs from that in a previously studied, unscreened population.
| S-EPMC5117796 | biostudies-literature
Project description:BackgroundThe 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.MethodsA 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.ResultsApproximately 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).ConclusionsAfter 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.
| S-EPMC3260132 | biostudies-literature
Project description:IntroductionIdentification 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.MethodsProspective 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.ResultsDuring 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.ConclusionThe PLCO lung cancer risk models demonstrate high discrimination and calibration.
| S-EPMC3131220 | biostudies-literature
Project description:BackgroundAdiposity traits have been associated with risk of many cancers in observational studies, but whether these associations are causal is unclear. Mendelian randomization (MR) uses genetic predictors of risk factors as instrumental variables to eliminate reverse causation and reduce confounding bias. We performed MR analyses to assess the possible causal relationship of birthweight, childhood and adult body mass index (BMI), and waist-hip ratio (WHR) on the risks of breast, ovarian, prostate, colorectal and lung cancers.MethodsWe tested the association between genetic risk scores and each trait using summary statistics from published genome-wide association studies (GWAS) and from 51 537 cancer cases and 61 600 controls in the Genetic Associations and Mechanisms in Oncology (GAME-ON) Consortium.ResultsWe found an inverse association between the genetic score for childhood BMI and risk of breast cancer [odds ratio (OR) = 0.71 per standard deviation (s.d.) increase in childhood BMI; 95% confidence interval (CI): 0.60, 0.80; P = 6.5 × 10(-5)). We also found the genetic score for adult BMI to be inversely associated with breast cancer risk (OR = 0.66 per s.d. increase in BMI; 95% CI: 0.57, 0.77; P = 2.5 × 10(-7)), and positively associated with ovarian cancer (OR = 1.35; 95% CI: 1.05, 1.72; P = 0.017), lung cancer (OR = 1.27; 95% CI: 1.09, 1.49; P = 2.9 × 10(-3)) and colorectal cancer (OR = 1.39; 95% CI: 1.06, 1.82, P = 0.016). The inverse association between genetically predicted adult BMI and breast cancer risk remained even after adjusting for directional pleiotropy via MR-Egger regression.ConclusionsFindings from this study provide additional understandings of the complex relationship between adiposity and cancer risks. Our results for breast and lung cancer are particularly interesting, given previous reports of effect heterogeneity by menopausal status and smoking status.
| S-EPMC6372135 | biostudies-literature
Project description:Red meat consumption has been positively associated with colorectal cancer; however, the biological mechanism underlying this relationship is not understood. Red meat is a major source of iron, which may play a role in colorectal carcinogenesis via increased crypt cell proliferation, cytotoxicity, and endogenous N-nitrosation. In a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we prospectively evaluated multiple iron exposure parameters, including dietary intake and serum measures of iron, ferritin, transferrin, total iron binding capacity (TIBC), and unsaturated iron binding capacity (UIBC) in relation to incident colorectal adenoma in 356 cases and 396 matched polyp-free controls. We also investigated variation in eight key genes involved in iron homeostasis in relation to colorectal adenoma in an additional series totaling 1,126 cases and 1,173 matched controls. We observed a positive association between red meat intake and colorectal adenoma [OR comparing extreme quartiles (OR(q4-q1)) = 1.59, 95% CI = 1.02-2.49, P(trend) = 0.03]. Serum TIBC and UIBC were inversely associated with colorectal adenoma (OR(q4-q1) = 0.57, 95% CI = 0.37-0.88, P(trend) = 0.03; and OR(q4-q1) = 0.62, 95% CI = 0.40-0.95, P(trend) = 0.04, respectively). Colorectal adenoma was not associated with serum ferritin, iron, or transferrin saturation or with polymorphisms in genes involved in iron homeostasis. Serum TIBC and UIBC, parameters that have a reciprocal relationship with overall iron load, were inversely related to colorectal adenoma, suggesting that individuals with lower iron status have a reduced risk of developing colorectal adenoma.
| S-EPMC3168068 | biostudies-literature