Association of Nonadherence to Cancer Screening Examinations With Mortality From Unrelated Causes: A Secondary Analysis of the PLCO Cancer Screening Trial

Abstract

Importance: Patient 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.

Objective: To 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 participants: Randomization 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 measures: Mortality 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.

Results: Of 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 relevance: Among 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 registration: ClinicalTrials.gov identifier: NCT00002540.

Figure 1.. Flowchart of Analysis Cohort

To be included in the analysis cohort, participants had to be in the intervention arm, have provided standard informed consent, have ovaries (if women), and have at least 1 year of follow-up after randomization. Adherent participants underwent all baseline screening tests, partially adherent participants underwent some but not all screening tests, and nonadherent participants underwent no baseline screening tests. PLCO indicates the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial.

Figure 2.. Mortality Rates by Time Period and Baseline Adherence Group

Deaths from cancers studied in the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial are excluded. Rates are adjusted for age (5-year groups), sex, and race/ethnicity (non-Hispanic white vs other) according to the overall cohort distribution.