Dataset Information

Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials.

ABSTRACT: Background:The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction. Objective:To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO. Design:Cox regression of prostate cancer death in each trial group, adjusted for age and trial. Extended analyses accounted for increased incidence due to screening and diagnostic work-up in each group via mean lead times (MLTs), which were estimated empirically and using analytic or microsimulation models. Setting:Randomized controlled trials in Europe and the United States. Participants:Men aged 55 to 69 (ERSPC) or 55 to 74 (PLCO) years at randomization. Intervention:Prostate cancer screening. Measurements:Prostate cancer incidence and survival from randomization; prostate cancer incidence in the United States before screening began. Results:Estimated MLTs were similar in the ERSPC and PLCO intervention groups but were longer in the PLCO control group than the ERSPC control group. Extended analyses found no evidence that effects of screening differed between trials (P = 0.37 to 0.47 [range across MLT estimation approaches]) but strong evidence that benefit increased with MLT (P = 0.0027 to 0.0032). Screening was estimated to confer a 7% to 9% reduction in the risk for prostate cancer death per year of MLT. This translated into estimates of 25% to 31% and 27% to 32% lower risk for prostate cancer death with screening as performed in the ERSPC and PLCO intervention groups, respectively, compared with no screening. Limitation:The MLT is a simple metric of screening and diagnostic work-up. Conclusion:After differences in implementation and settings are accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality. Primary Funding Source:National Cancer Institute.

SUBMITTER: Tsodikov A

PROVIDER: S-EPMC5734053 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials.

Tsodikov Alex A Gulati Roman R Heijnsdijk Eveline A M EAM Pinsky Paul F PF Moss Sue M SM Qiu Sheng S de Carvalho Tiago M TM Hugosson Jonas J Berg Christine D CD Auvinen Anssi A Andriole Gerald L GL Roobol Monique J MJ Crawford E David ED Nelen Vera V Kwiatkowski Maciej M Zappa Marco M Luján Marcos M Villers Arnauld A Feuer Eric J EJ de Koning Harry J HJ Mariotto Angela B AB Etzioni Ruth R

Annals of internal medicine 20170905 7

<h4>Background</h4>The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction.<h4>Objective</h4>To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO.<h4>Design</h4>Cox regression of prostate cancer death in each trial group, adjusted for age and trial. Exte ...[more]

PMID: 28869989

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Project description:BACKGROUND:The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years. METHODS:ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55-69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50-74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years' follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736. FINDINGS:With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83-1·99) after 9 years (1·64 [1·58-1·69] including France), 1·66 (1·60-1·73) after 11 years, and 1·57 (1·51-1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70-1·03) after 9 years, 0·78 (0·66-0·91) after 11 years, and 0·79 (0·69-0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490-1929) men invited for screening or one per 27 (17-66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61-0·88). INTERPRETATION:In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening. FUNDING:Each centre had its own funding responsibility.

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.

Project description:ImportancePatient nonadherence to chronic disease prevention guidelines is associated with increased mortality. Nonadherence to offered cancer screening tests may be associated with mortality among middle-aged and older adults.ObjectiveTo evaluate the association between nonadherence to cancer screening tests and mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial, excluding mortality from cancers studied in the trial.Design, setting, and participantsRandomization at 10 US screening centers occurred from November 8, 1993, to July 2, 2001. Original follow-up was through 13 years or December 31, 2009. Participants were re-consented to further follow-up starting May 18, 2011, and were observed until December 31, 2012. Protocol screening tests for the PLCO Cancer Screening trial intervention arm participants (N = 77 443) included chest radiographs and flexible sigmoidoscopy for both sexes, prostate-specific antigen tests and digital rectal examinations for men, and cancer antigen 125 tests and transvaginal ultrasonography for women. At baseline, participants completed a self-administered questionnaire. The cohort was classified into those receiving all sex-specified PLCO Cancer Screening trial screening tests at baseline (fully adherent), those receiving some but not all baseline tests (partially adherent), and those receiving no baseline tests (nonadherents). Secondary analysis was ad hoc in the original trial protocol. Statistical analysis was conducted from November 24, 2017, to August 29, 2018.Main outcomes and measuresMortality was ascertained via mailed annual study update questionnaires and searches of the National Death Index. Cox proportional hazards regression was used to analyze the association between mortality and adherence, controlling for various covariates.ResultsOf 77 443 participants in the intervention arm, 64 567 (29 537 women and 35 030 men; mean [SD] age, 62.3 [5.3] years) were included in the analysis based on consenting to trial participation before randomization and being eligible for all screening tests. Overall, 55 065 participants (85.3%) were adherent, 2548 (3.9%) were partially adherent, and 6954 (10.8%) were nonadherent with the baseline screening protocol. Within 10 years of follow-up, the hazard ratio of mortality, excluding deaths from cancers studied in the PLCO Cancer Screening trial and controlling only for age, sex, and race/ethnicity (model 1), was 1.73 (95% CI, 1.60-1.89) for nonadherent compared with fully adherent participants and 1.36 (95% CI, 1.19-1.54) for partially compared with fully adherent participants. After adjustment for medical risk factors for mortality and behavioral-related factors (model 2), the hazard ratio decreased to 1.46 (95% CI, 1.34-1.59) for nonadherent compared with fully adherent participants.Conclusions and relevanceAmong participants in a screening trial for multiple cancers, a nonadherence behavior profile marked by nonadherence to protocol screenings was associated with higher overall mortality (excluding deaths from cancers studied in the trial). The generalizability of this finding to routine clinical practice should be assessed.Trial registrationClinicalTrials.gov identifier: NCT00002540.

Dataset Information

Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials.

Publications

Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials.

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