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

Abstract

See accompanying editorial on page 4310To identify factors related to who undergoes a prostate biopsy in a screened population and to estimate the impact of biopsy verification on risk factor-prostate cancer associations. Patients and MethodsMen who were screened regularly from the placebo arms of two large prostate cancer prevention trials (Prostate Cancer Prevention Trial [PCPT] and Selenium and Vitamin E Cancer Prevention Trial [SELECT]) were examined to define incident prostate cancer cohorts. Because PCPT had an end-ofstudy biopsy, prostate cancer cases were categorized by a preceding prostate-specific antigen/digital rectal examination prompt (yes/no) and noncases by biopsy-proven negative status (yes v no). We estimated the association of risk factors (age, ethnicity, family history, body mass index, medication use) with prostate cancer and quantified differences in risk associations across cohorts. ResultsMen 60 to 69 years of age, those with benign prostatic hyperplasia, and those with a family history of prostate cancer were more likely, and those with a higher body mass index ($ 25), diabetes, or a smoking history were less likely, to undergo biopsy, adjusting for age and longitudinal prostatespecific antigen and digital rectal examination. Medication use, education, and marital status also influenced who underwent biopsy. Some risk factor estimates for prostate cancer varied substantially across cohorts. Black (v other ethnicities) had odds ratios (ORs) that varied from 1.20 for SELECT (community screening standards, epidemiologic-like cohort) to 1.83 for PCPT (end-of-study biopsy supplemented with imputed end points). Statin use in SELECT provided an OR of 0.65 and statin use in in PCPT provided an OR of 0.99, a relative difference of 34%. ConclusionAmong screened men enrolled in prostate cancer prevention trials, differences in risk factor estimates for prostate cancer likely underestimate the magnitude of bias found in other cohorts with varying screening and biopsy recommendations and acceptance. Risk factors for prostate cancer derived from epidemiologic studies not only may be erroneous but may lead to misdirected research efforts.

Aspirin and Non-Aspirin NSAID Use and Prostate Cancer Incidence, Mortality, and Case Fatality in the Atherosclerosis Risk in Communities Study

“…At first glance, our finding of no association between aspirin and prostate cancer incidence appears inconsistent with prior studies, which have most often reported inverse associations (8). However, our primary analysis did not account for detection bias resulting from the fact that aspirin users may be more healthconscious, or in greater contact with the healthcare system, and thus more likely to be screened for prostate cancer (22). To account for this bias, we stratified by frequency of routine visits to the doctor, a proxy for opportunity to undergo prostate cancer screening.…”

Age dependence of modern clinical risk groups for localized prostate cancer—A population‐based study

“…We note that the diagnosis of localized PCa is typically made by biopsy, and the several decisions, by both clinician and patient, that might lead to a biopsy procedure also afford the potential for bias in who is diagnosed . In addition, some Norwegian men diagnosed with aggressive disease at an older age might have been diagnosed with less aggressive disease at a younger age had they undergone frequent screening.…”

“…We note that the diagnosis of localized PCa is typically made by biopsy, and the several decisions, by both clinician and patient, that might lead to a biopsy procedure also afford the potential for bias in who is diagnosed. 39 In addition, some Norwegian men diagnosed with aggressive disease at an older age might have been diagnosed with less aggressive disease at a younger age had they undergone frequent screening. It is unclear how much this hypothetical situation might have affected the actual results found here, but it would be consistent with the overall pattern demonstrated here of increased risk of more advanced disease with age.…”

A Magnetic Resonance Imaging–Based Prediction Model for Prostate Biopsy Risk Stratification

“…This factor could contribute to verification bias. 20 It is, however, well known that the likelihood of clinically significant prostate cancer in patients with negative results of multiparametric MRI is low. 21 Thus, on one hand, patients with negative MRI results are unlikely to benefit from a biopsy.…”