Baseline subject characteristics predictive of compliance with study-mandated prostate biopsy in men at risk of prostate cancer: results from REDUCE

Abstract

IntroductionStudy compliance is crucial when the study outcome is determined by an invasive procedure, such as prostate biopsy. To investigate predictors of compliance in study-mandated prostate biopsies, we analyzed demographic, clinical and reported lifestyle data from the REDUCE trial.MethodsWe retrospectively identified 8,025 men from REDUCE with at least 2-years of follow-up, and used multivariable logistic regression to test the association between baseline demographic and clinical characteristics and undergoing the study-mandated prostate biopsy at 2 years. We then examined whether missing any of these data was associated with undergoing a biopsyResultsIn REDUCE, 22% of men did not undergo a 2-year biopsy. On multivariable analysis, non-North American region was predictive of 42-44% increased likelihood of undergoing a 2-year biopsy (p≤0.001). Being enrolled at a center that enrolled >10 subjects (2nd and 3rd tertile) was associated with a 42-48% increased likelihood of undergoing a 2-year biopsy (p<0.001). Additionally, black race predicted 44% lower rate of on-study 2-year biopsy (OR=0.56; p=0.001). Finally, missing one or more baseline variables was associated with a 32% decreased likelihood of undergoing a 2-year biopsy (OR=0.68; p<0.001).ConclusionsIn REDUCE, men outside North America, those at higher volume centers, and those with complete baseline data were more likely to undergo study mandated 2-year biopsies. Given prostate biopsy is becoming increasingly utilized as an endpoint in trials that are often multi-national, regional differences in compliance should be considered when designing future trials. Likewise, efforts are needed to ensure compliance in low-volume centers or among subjects missing baseline data.

Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study

“…Moreover, observational studies are rarely able to control for biopsy compliance, which differs by obesity and obesity-associated co-morbidity status. 14 , 15 Data from the PCPT chemoprevention trial that, like REDUCE, implemented trial-mandated PSA-independent biopsies, showed that men with low serum cholesterol had lower high-grade prostate cancer risk. As such, our study builds on evidence for a cholesterol-prostate cancer link in the context of PSA-independent, trial-mandated biopsies where all men had equal opportunity for prostate cancer diagnosis.…”

“…Serum cholesterol is positively correlated with serum prostate-specific antigen (PSA), 12 , 13 potentially leading to increased PSA-driven biopsy rates and more prostate cancer diagnoses among men with high cholesterol. Conversely, obesity-associated comorbidities including hypercholesterolemia have been associated with lower biopsy compliance, 14 , 15 potentially leading to fewer prostate cancer diagnoses among men with high cholesterol.…”

Racial differences in prostate inflammation: results from the REDUCE study

“…Age, race and family history are well-established PC risk factors. PC rates in Asians are lower than in whites and Hispanics, while black men are disproportionally affected by PC [ 12 ]. The reasons for these disparities are unclear.…”

Biases in Recommendations for and Acceptance of Prostate Biopsy Significantly Affect Assessment of Prostate Cancer Risk Factors: Results From Two Large Randomized Clinical Trials

“…Although there have been reports of factors associated with biopsy compliance in PCPT 9 and Reduction by Dutasteride of Prostate Cancer Events study (REDUCE), 10,11 to our knowledge, this is the first systematic evaluation of how biases related to prostate cancer ascertainment may affect our understanding of disease risk factors. The potential for such bias is substantial because, if all men underwent prostate biopsy, at least 15% would be diagnosed with cancer.…”