title: Targeted Biopsy to Detect Gleason Score Upgrading during Active Surveillance for Men with Low versus Intermediate Risk Prostate Cancer.
abstract: We sought to determine the rate of upgrading to Gleason score 4 + 3 or greater using targeted biopsy for diagnosis and monitoring in men undergoing active surveillance of prostate cancer.
  
  
  
  Study subjects comprised all 259 men, including 196 with Gleason score 3 + 3 and 63 with Gleason score 3 + 4, who were diagnosed by magnetic resonance imaging/ultrasound fusion guided biopsy from 2009 to 2015 and underwent subsequent fusion biopsy for as long as 4 years of active surveillance. The primary end point was the discovery of Gleason score 4 + 3 or greater prostate cancer. Followup biopsies included targeting of positive sites, which were tracked in an Artemis™ device. Kaplan-Meier curves were generated to determine upgrading rates, stratified by initial Gleason score and prostate specific antigen density.
  
  
  
  Based on a Cox proportional hazard model, men with Gleason score 3 + 4 were 4.65 times more likely to have upgrading than men with an initial Gleason score of 3 + 3 at 3 years (p <0.01). By the third surveillance year 63% of men with Gleason score 3 + 4 had been upgraded compared with 18.0% who started with Gleason score 3 + 3 (p <0.01). Of all 33 upgrades 32 (97%) occurred at a magnetic resonance imaging visible or a tracked site of tumor, rather than at a previously negative systematic site. Independent predictors of upgrading were Gleason score 3 + 4, prostate specific antigen density 0.15 ng/ml/cm3or greater and a grade 5 lesion on magnetic resonance imaging. The incidence rate ratio of upgrading (Gleason score 3 + 4 vs 3 + 3) was 4.25 per year of patient followup (p <0.01).
  
  
  
  During active surveillance of prostate cancer, targeting of tracked tumor foci by magnetic resonance imaging/ultrasound fusion biopsy allows for heightened detection of Gleason score 4 + 3 or greater cancers. Baseline variables directly related to important upgrading that warrant increased vigilance include Gleason score 3 + 4, prostate specific antigen density 0.15 ng/ml/cm3or greater and grade 5 lesions on magnetic resonance imaging.
authors.affiliation: Department of Urology (NN, SN, DSS, LSM), University of California-Los Angeles, Los Angeles, California; Department of Radiology (DJM), University of California-Los Angeles, Los Angeles, California; Department of Biomedical Engineering (SN), University of California-Los Angeles, Los Angeles, California; Department of Pathology, Duke University School of Medicine (JH), Durham, North Carolina.
authors.forename: Nima
authors.initials: N
authors.lastname: Nassiri
authors.affiliation: Department of Urology (NN, SN, DSS, LSM), University of California-Los Angeles, Los Angeles, California; Department of Radiology (DJM), University of California-Los Angeles, Los Angeles, California; Department of Biomedical Engineering (SN), University of California-Los Angeles, Los Angeles, California; Department of Pathology, Duke University School of Medicine (JH), Durham, North Carolina.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Margolis
authors.affiliation: Department of Urology (NN, SN, DSS, LSM), University of California-Los Angeles, Los Angeles, California; Department of Radiology (DJM), University of California-Los Angeles, Los Angeles, California; Department of Biomedical Engineering (SN), University of California-Los Angeles, Los Angeles, California; Department of Pathology, Duke University School of Medicine (JH), Durham, North Carolina.
authors.forename: Shyam
authors.initials: S
authors.lastname: Natarajan
authors.affiliation: Department of Urology (NN, SN, DSS, LSM), University of California-Los Angeles, Los Angeles, California; Department of Radiology (DJM), University of California-Los Angeles, Los Angeles, California; Department of Biomedical Engineering (SN), University of California-Los Angeles, Los Angeles, California; Department of Pathology, Duke University School of Medicine (JH), Durham, North Carolina.
authors.forename: Devi S
authors.initials: DS
authors.lastname: Sharma
authors.affiliation: Department of Urology (NN, SN, DSS, LSM), University of California-Los Angeles, Los Angeles, California; Department of Radiology (DJM), University of California-Los Angeles, Los Angeles, California; Department of Biomedical Engineering (SN), University of California-Los Angeles, Los Angeles, California; Department of Pathology, Duke University School of Medicine (JH), Durham, North Carolina.
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Urology (NN, SN, DSS, LSM), University of California-Los Angeles, Los Angeles, California; Department of Radiology (DJM), University of California-Los Angeles, Los Angeles, California; Department of Biomedical Engineering (SN), University of California-Los Angeles, Los Angeles, California; Department of Pathology, Duke University School of Medicine (JH), Durham, North Carolina.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Dorey
authors.affiliation: Department of Urology (NN, SN, DSS, LSM), University of California-Los Angeles, Los Angeles, California; Department of Radiology (DJM), University of California-Los Angeles, Los Angeles, California; Department of Biomedical Engineering (SN), University of California-Los Angeles, Los Angeles, California; Department of Pathology, Duke University School of Medicine (JH), Durham, North Carolina. Electronic address: Lmarks@mednet.ucla.edu.
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Marks
mesh_terms: D006801:Humans; D061705:Image-Guided Biopsy / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D064847:Multimodal Imaging; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000473:pathology*; D012306:Risk; D014463:Ultrasonography; D057832:Watchful Waiting
keywords: image-guided biopsy; magnetic resonance imaging; prostatic neoplasms; ultrasonography; watchful waiting