Risk Of Biopsy-detectable Prostate Cancer Research Articles

Assessing a patient’s individual risk of biopsy-detectable prostate cancer: Be aware of case mix heterogeneity and a priori likelihood

The relation between prostate-specific antigen (PSA) and other relevant prebiopsy information is often combined in a risk calculator (RC). If the setting for RC use differs from that in which it was developed, there is a risk of making clinical decisions based on incorrect estimates of the absolute risk. The ERSPC-MRI RC predicts clinically significant prostate cancer (csPC; Gleason ≥ 3 + 4) on targeted and systematic biopsy using information on PSA, digital rectal examination, prostate volume, age, previous negative biopsy, and Prostate Imaging-Recording and Data System score. This calculator was developed on a clinical cohort of 961 men (2012–2017) with a csPC prevalence of 36%. Discrimination was good (area under the receiver operating characteristic curve 0.84). With the increasing use of multiparametric magnetic resonance imaging, we foresee that this RC will also be used for men with a lower a priori likelihood of PC. We investigated the effect of such a scenario on individual risk predictions. A small update of the intercept for the calculator can restore the accuracy to support decision-making with locally valid risk estimates. Patient summaryDecisions on who to refer for a prostate biopsy with its risk of sepsis and overdiagnosis require more than a prostate-specific antigen test. A prediction tool may take other relevant prebiopsy information into account, but may need to be updated to contemporary center-specific settings to provide accurate estimates of the risk of having prostate cancer.

The risk of biopsy-detectable prostate cancer using the prostate cancer prevention Trial Risk Calculator in a community setting

Materials and methodsRisks of prostate cancer (CaP) and high-grade CaP were evaluated using the Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) in an age-stratified random sample of 1,021 Caucasian and African-American men with no previous diagnosis of CaP, aged 55–74 years, residing in King County, WA, USA. ResultsMedian PCPTRC risks of CaP (high-grade CaP) were 15.6% (1.2%), 18.7% (2.0%), 18.5% (2.2%), and 26.4% (5.1%) for 55–59, 60–64, 65–69, and 70–74-year-old men, respectively; 25.2% of men aged 55–59 had a 25% or greater PCPTRC risk of CaP; this increased to 53.1% in men aged 70–74; 9.4% of men aged 55–59 had a 6% or greater PCPTRC risk of high-grade CaP, increasing to 44.1% in men aged 70–74. ConclusionsPCPTRC risk of CaP in a community of US males is high and confounded with overdetected cancers. In contrast, average community PCPTRC risk of high-grade disease is low and increases gradually by age and may better serve for counseling purposes.

Usefulness of prostate‐specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study

To determine if dutasteride-treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. To analyse whether the use of treatment-specific criteria for repeat biopsy maintains the usefulness of prostate-specific antigen (PSA) level for detecting high grade cancers. The REDUCE study was a randomized, double-blind, placebo-controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsy-detectable prostate cancer in men with a previous negative biopsy. The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds. Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8-10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8-10 cancers would have been missed in the placebo group. In both groups, the incidence of Gleason 7 and Gleason 8-10 cancers generally increased with greater rises in PSA. Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7-10 cancers in men treated with dutasteride vs placebo. Men with Gleason 7 and Gleason 8-10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds. Using treatment-specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8-10) or higher than (Gleason 7-10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.

Conference Report: Eighth Annual AACR International Conference on Frontiers in Cancer Prevention Research

The Eighth Annual Frontiers in Cancer Prevention Research meeting was held in Houston, Texas, in November 2009. This report highlights significant presentations that advance the fields of chemoprevention, clinical trial recruitment and retention, cancer screening including optical imaging, energy balance, and nutritional epidemiology, and health communications and decision making. In findings from the randomized Reduction by Dutasteride of Prostate Cancer Events trial, dutasteride reduced the risk of biopsy-detectable prostate cancer in high-risk men by 23% compared with placebo. Important clues about the dosing and window of susceptibility for supplementation with choline, vitamin D, and folate were revealed from epigenetic research that has implications for future nutritional epidemiology research. Noninvasive optical imaging techniques using endoscopic ultrasound and autofluorescence for the early detection of cancers in the lung, pancreas, and oral cavity are being studied. The report also addresses the challenges of promoting cancer prevention. Understanding how individuals process risk information and make sustained behavior changes and the effect of socioeconomic status on health disparities were identified as critical areas of research. This multidisciplinary research meeting of basic, clinical, and behavioral scientists and epidemiologists continues to play a major role in identifying the research priority areas of cancer prevention, elucidating new mechanisms of carcinogenesis for targeted chemoprevention therapies and delivering a comprehensive strategy for engaging individuals in the unifying goal to reduce cancer incidence.

Dutasteride reduces the risk of biopsy-detectable prostate cancer and BPH complications among men at increased prostate cancer risk with concomitant BPH: sub-analysis from the REDUCE study

Dutasteride reduces the risk of biopsy-detectable prostate cancer and BPH complications among men at increased prostate cancer risk with concomitant BPH: sub-analysis from the REDUCE study

INCIDENCE OF BIOPSY-DETECTABLE PROSTATE CANCER IN THE REDUCTION BY DUTASTERIDE OF PROSTATE CANCER EVENTS (REDUCE) TRIAL: BLINDED 2-YEAR RESULTS

INTRODUCTION AND OBJECTIVE: In the pre-planned analysis of the REDUCE study, the incidence of biopsy-detectable prostate cancer (PCa) is summarized using several methods, which yield different observed rates of PCa incidence. METHODS: REDUCE is an ongoing 4-year, international, randomized, double-blind, placebo-controlled, parallel-group study investigating the efficacy of dutasteride in reducing the risk of biopsydetectable prostate cancer. Eligible subjects were aged 5075 years, with a serum prostate specific antigen (PSA) 2.5-10 ng/mL (men aged 50-60 years) or 3.0-10 ng/mL (men aged >60 years) and a single, negative biopsy of 6-12 cores within 6 months prior to enrollment. After 2 and 4 years of treatment, transrectal ultrasound directed biopsies (10 cores) were performed. Blinded 2-year PCa results for all subjects are available and are summarized using crude, restricted crude, and modified crude rate methods. RESULTS: Definitions for each of the 3 methods for calculation of prostate cancer incidence are listed in the table below along with the actual calculated blinded 2-year results for subjects in the efficacy population (subjects with no PCa in baseline biopsy as assessed by the central pathology lab and who took at least one dose of study medication; n=8108). Blinded 2-year PCa rates in REDUCE