Search

Several liquid biomarker tests have been developed to account for the limitations of prostate specific antigen (PSA) screening prior to prostate biopsy. African ancestry is an established risk factor for prostate cancer (PCa) and must be particularly considered when evaluating patients with liquid biomarkers. While multiple tests have been developed over decades of exploration, recent advances can help patients and physicians incorporate data into a broader clinical context.We sought to review currently available liquid biomarker tests in a practical, clinically directed fashion with particular focus on performance in men with African ancestry. We reviewed discovery and validation studies and highlight important considerations for each test.We discuss the advantages and limitations of percent free PSA, Prostate Health Index, Progensa® PCA3, ExoDx® Prostate Test, SelectMDx®, 4Kscore® Test, and Mi-Prostate Score and summarize salient studies on their use. A literature review of evidence specifically for men with African ancestry was conducted and available studies were summarized.Liquid biomarkers can be useful tools for aiding in risk stratification prior to prostate biopsy. Use of such tests should be individualized based on a thorough knowledge of supporting evidence and the goals of the patient and physician. Further study should prioritize evaluation of such biomarkers in men with African ancestry.

Nocturia (voids arising from sleep) is a ubiquitous phenomenon reflecting many diverse conditions but whether it has significance in its own right remains uncertain. We examined whether nocturia was an independent risk factor for mortality These were observational analyses employing primarily North American and European participants and included 7343 men, aged 50–75 years participating in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial. Cox proportional hazards models were used to test the association between baseline nocturia (voiding ≥3 times per night) and all-cause mortality. Potential confounding variables included: age; race; region of origin; treatment group; self-reported coronary artery disease, diabetes mellitus, hypertension, and peripheral vascular disease; smoking; alcohol use; prostate volume; and diuretics. Self-reported sleep quality, as measured with the Medical Outcomes Study sleep scale, was entered as a final step in the model. Nocturia was associated with increased mortality risk (hazard ratio [HR] = 1.72; 95% CI 1.15–2.55) independent from demographics and medical comorbidities. Inclusion of disturbed sleep in the model reduced the magnitude of the association (HR = 1.43; 95% CI 0.93–2.19). Although the findings are limited to men, half of whom ingested dutasteride, the interruption of sleep by nocturia may have long-term impact on health and may warrant targeted intervention.

Prostate atrophy (PA) is commonly identified in prostate biopsies. Previous studies suggest PA may be associated with lower PCa risk. However, it remains unclear whether PA is associated with smaller, less aggressive, and less advanced tumors. Thus, we sought to determine whether the presence and severity of baseline PA in men with initial biopsy negative for prostate cancer (PCa) is associated with PCa volume at 2- and 4-year repeat biopsy. We performed a retrospective analysis of 927 men 50–75-years-old with negative baseline biopsy and positive 2- or 4-year repeat biopsy for PCa in the Reduction by Dutasteride of PCa Events study. PA (present or absent), PA severity (mild or moderate/marked), and tumor volume were determined by central pathology. The association of baseline PA with repeat biopsy PCa volume was evaluated with linear and Poisson regressions in uni- and multivariable analyses. PA was identified in 559 (60%) baseline biopsies and was mild in 491 (88%) and moderate/marked in 68 (12%). PA was associated with larger prostate volumes (P

BACKGROUND Study 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. METHODS We retrospectively identified 8025 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 biopsy. RESULTS In REDUCE, 22% of men did not undergo a 2-year biopsy. On multivariable analysis, the 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

The relationship between baseline prostate-specific antigen (PSA) and development of lower urinary tract symptoms (LUTS) in asymptomatic and mildly symptomatic men is unclear. We sought to determine if PSA predicts incident LUTS in these men. A post-hoc analysis of the 4-year REDUCE study was performed to assess for incident LUTS in 1534 men with mild to no LUTS at baseline. The primary aim was to determine whether PSA independently predicted incident LUTS after adjusting for the key clinical variables of age, prostate size, and baseline International prostate symptom score (IPSS). Incident LUTS was defined as the first report of medical treatment, surgery, or sustained clinically significant symptoms (two IPSS >14). Cox proportional hazards, cumulative incidence curves, and the log-rank test were used to test our hypothesis. A total of 1534 men with baseline IPSS

To evaluate whether the presence of both prostate atrophy (PA) and chronic prostate inflammation (CPI) in the same biopsy and in the same biopsy core are associated with prostate cancer (PCa) risk and grade in repeat biopsies. Retrospective analyses of 6132 men who were 50–75 years old undergoing 2-year repeat prostate biopsy after a negative baseline biopsy for PCa in the REduction by DUtasteride of prostate Cancer Events (REDUCE) study. PA, CPI and PCa were determined by central pathology. The association of baseline PA and CPI with 2-year repeat biopsy cancer status and grade was evaluated with χ2 test and logistic regression controlling clinicopathological features. PA, CPI and both were detected in 583 (9.5%), 1063 (17.4%) and 3675 (59.9%) baseline biopsies, respectively. Compared with biopsies with neither PA nor CPI, the presence of PA (odds ratio (OR)=0.73, 95% confidence interval (CI)=0.57–0.93), CPI (OR=0.72, 95% CI=0.58–0.88) and both (OR=0.54, 95% CI=0.45–0.64) were associated with lower PCa risk in the 2-year repeat prostate biopsy. Results were similar in multivariable analysis. Among subjects with both PA and CPI, those with both findings in the same core had even lower PCa risk compared with PA and CPI in different cores (univariable OR=0.68, 95% CI=0.51–0.91; multivariable OR=0.73, 95% CI=0.54–0.99). Combination of PA and CPI was associated with lower risk of high-grade PCa. The presence of both PA and CPI in baseline biopsies, especially in the same core, was associated with lower PCa risk and grade. The presence and topographical distribution of PA and CPI may be used in PCa risk stratification.

Statins are associated with lower PSA levels. As PSA is the primary method for prostate cancer (PC) screening, this confounds any associations between statins and risk of being diagnosed with PC. Thus, we examined the association between statins and cancer and high-grade cancer in REDUCE, where biopsies were largely PSA-independent.Post-hoc secondary analysis of REDUCE, which was a prospective multinational randomized controlled trial of dutasteride vs placebo for 4 years among men aged 50-75 years with PSA of 2.5-10.0 ng ml(-1) and a negative biopsy at baseline, and included PSA-independent biopsies mandated at 2- and 4-years. Analyses were limited to men who underwent at least one biopsy while under study (n=6729). The association between baseline statin use and risk of overall, high-grade (Gleason ≥ 7) or low-grade (Gleason ≤ 6) PC vs no cancer was examined using multinomial logistic regression adjusting for age, race, baseline PSA, prostate volume, rectal examination findings, body mass index (BMI), comorbidities, smoking, alcohol intake and treatment arm.Of 6729 men who had at least one biopsy while on study, 1174 (17.5%) were taking a statin at baseline. Men taking statins were older, had lower PSA levels, higher BMI values and lower serum testosterone and dihydrotestosterone levels, though differences, were slight. Statin use was not associated with overall PC diagnosis (multivariable OR 1.05, 95% CI 0.89-1.24, P=0.54). When stratified by grade, statin use was not associated with low-grade (multivariable OR 1.03, 95% CI 0.85-1.25, P=0.75) or high-grade cancer (multivariable OR 1.11, 95% CI 0.85-1.45, P=0.46). The major limitation is the inclusion of only men with a negative baseline biopsy.Among men with a negative baseline biopsy and follow-up biopsies largely independent of PSA, statins were not associated with cancer or high-grade cancer.

Men with diabetes mellitus are less likely to be diagnosed with prostate cancer (PCa). As diabetic men have lower serum PSA, it is unclear if this is due to lower PCa incidence or reflects detection bias from fewer PSA-triggered biopsies. To account for differential biopsy rates, we used multivariate regression to examine the link between diabetes and PCa risk in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which required all subjects to undergo biopsy regardless of PSA. We further tested for interaction between diabetes and obesity. Diabetes status and body mass index (BMI) measurements were obtained at baseline. On multivariate analysis, diabetes was not associated with PCa risk (odds ratio (OR) 1.01, 95% confidence interval 0.79-1.30, P=0.92) or risk of low- or high-grade disease (all P ≥ 0.65). When stratified by obesity, diabetes was also not associated with PCa risk in any BMI category (all P ≥ 0.15). However, there was suggestion of effect modification by obesity for high-grade disease (P-interaction=0.053). Specifically, diabetes was associated with decreased risk of high-grade PCa in normal-weight men but increased risk in obese men (OR 0.35 vs 1.38). In the REDUCE trial, when all men underwent biopsy, diabetes was not associated with lower PCa risk, but rather equal risk of PCa, low-grade PCa and high-grade PCa.