An analysis of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening trial found that forgoing screening was associated with an increased risk for death due to respiratory diseases, digestive diseases, cardiovascular diseases, and other non-screened cancers compared with fully adhering to the screening protocol.
Excluding deaths from the cancers being screened for in the trial and controlling for age, sex, and race/ethnicity, participants who were nonadherent had a 73% increased risk for death compared with fully adherent participants (HR 1.73, 95% CI 1.60-1.89), according to Dudith Pierre-Victor, PhD, and Paul F. Pinsky, PhD, both of the National Cancer Institute in Bethesda, Maryland.
After adjusting the data for medical risk factors for mortality and behavioral-related factors such as marriage and education, the HR for death decreased to 1.46 for nonadherent participants compared with fully adherent participants (95% CI 1.34-1.59).
Participants who were partially adherent had an increased risk for death as well (HR 1.36, 95% CI 1.19-1.54), as reported in JAMA Internal Medicine.
According to the researchers, this increased risk could be explained by nonadherence to other guidelines for cancer screening, chronic disease prevention, or medical tests and treatment.
“These findings have implications for the interpretation of screening and other prevention trials with mortality endpoints,” the authors wrote. “Because a nonadherence phenotype is associated with higher mortality for causes that are not related to the trial, that phenotype may also convey higher risk for the cause of interest, irrespective of the effect of the intervention being studied.”
In an editorial published with the study, Deborah Grady, MD, MPH, and Monica Parks, MD, of the University of California San Francisco, noted that “there is no way that nonadherence with cancer screening could cause increased mortality from a range of diseases not associated with screening.”
Instead, a patient’s nonadherence may be an indication of behaviors that are associated with increased mortality, they explained.
“Previous studies have shown that patients who are adherent to recommended medications are more likely to seek out other preventive services such as screenings and vaccinations, while nonadherence has been associated with increased mortality,” wrote Grady and Parks. These biases, called adherence bias or compliance bias, is a form of “unmeasured confounding.”
The observational analysis included data from the PLCO Cancer Screening trial, which was conducted at 10 U.S. screening centers from 1993 to 2001. In PLCO, more than 75,000 patients underwent screening interventions that included chest radiographs and flexible sigmoidoscopy for all patients, prostate-specific antigen (PSA) tests and digital rectal examinations for men, and cancer antigen 125 tests and transvaginal ultrasonography for women.
The new analysis from Pierre-Victor and Pinsky included 64,567 of the eligible participants. Based on the number of screening tests they received, participants were classified as fully adherent (85.3%), partially adherent (3.9%), or nonadherent (10.8%) to the screening protocol.
“Although we believe that such a general nonadherence phenotype explains the preponderance of the increased risk associated with nonadherence observed in this study, it cannot be ruled out that reverse causation bias may explain a portion of the increased risk,” Pierre-Victor and Pinsky wrote. “Specifically, some participants may have had an underlying condition(s) at baseline, perhaps incompletely captured by our comorbidity variables, that both made it harder to comply with screening and predisposed the participants to earlier mortality.”
The study authors and editorialists reported no conflict of interest.