title: Expressed prostatic secretion biomarkers improve stratification of NCCN active surveillance candidates: performance of secretion capacity and TMPRSS2:ERG models.
abstract: OBJECTIVE
  Active surveillance is a viable patient option for prostate cancer provided that a clinical determination of low risk and presumably organ confined disease can be made. To standardize risk stratification schemes the NCCN (National Comprehensive Cancer Network®) provides guidelines for the active surveillance option. We determined the effectiveness of expressed prostatic secretion biomarkers for detecting occult risk factors in NCCN active surveillance candidates.
  
  
  METHODS
  Expressed prostatic secretion specimens were obtained before robot-assisted radical prostatectomy. Secretion capacity biomarkers, including total RNA and expressed prostatic secretion specimen volume, were measured by standard techniques. RNA expression biomarkers, including TXNRD1 mRNA, prostate specific antigen mRNA, TMPRSS2:ERG fusion mRNA and PCA3 mRNA, were measured by quantitative reverse-transcription polymerase chain reaction.
  
  
  RESULTS
  Of the 528 patients from whom expressed prostatic secretions were collected 216 were eligible for active surveillance under NCCN guidelines. Variable selection on logistic regression identified 2 models, including one featuring types III and VI TMPRSS2:ERG variants, and one featuring 2 secretion capacity biomarkers. Of the 2 high performing models the secretion capacity model was most effective for detecting cases in this group that were up-staged or up-staged plus upgraded. It decreased the risk of up-staging in patients with a negative test almost eightfold and decreased the risk of up-staging plus upgrading about fivefold while doubling the prevalence of up-staging in the positive test group.
  
  
  CONCLUSIONS
  Noninvasive expressed prostatic secretion testing may improve patient acceptance of active surveillance by dramatically reducing the presence of occult risk factors among those eligible for active surveillance under NCCN guidelines.
authors.affiliation: Division of Urology, City of Hope, Duarte, California.
authors.forename: Christopher
authors.initials: C
authors.lastname: Whelan
authors.affiliation: Division of Urology, City of Hope, Duarte, California.
authors.forename: Mark
authors.initials: M
authors.lastname: Kawachi
authors.affiliation: Division of Biostatistics, City of Hope, Duarte, California.
authors.forename: David D
authors.initials: DD
authors.lastname: Smith
authors.affiliation: Division of Urology, City of Hope, Duarte, California.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Linehan
authors.affiliation: Division of Urology, City of Hope, Duarte, California.
authors.forename: Gail
authors.initials: G
authors.lastname: Babilonia
authors.affiliation: Clinical Research Information Support, City of Hope, Duarte, California.
authors.forename: Rosa
authors.initials: R
authors.lastname: Mejia
authors.affiliation: Division of Urology, City of Hope, Duarte, California.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wilson
authors.affiliation: Division of Urology, City of Hope, Duarte, California; Beckman Research Institute, City of Hope, Duarte, California. Electronic address: ssmith@coh.org.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Smith
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis; D017410:Practice Guidelines as Topic; D011467:Prostate / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D012333:RNA, Messenger; D018570:Risk Assessment; D012307:Risk Factors; D054481:Thioredoxin Reductase 1 / Q000096:biosynthesis; D057832:Watchful Waiting
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C515553:TMPRSS2-ERG fusion protein, human; C479341:prostate cancer antigen 3, human; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D017430:Prostate-Specific Antigen
keywords: AS; DRE; ECE; EPS; PCA3; PCR; PCa; PSA; TMPRSS2:ERG; TXNRD1; active surveillance; bodily secretions; digital rectal examination; expressed prostatic secretion; extracapsular extension; neoplasm staging; polymerase chain reaction; prostate; prostate cancer; prostate cancer antigen 3 (nonprotein coding); prostate specific antigen; prostatic neoplasms; qPCR; quantitative PCR; risk; thioredoxin reductase 1; transmembrane protease, serine 2 gene fusion with v-ets erythroblastosis virus E26 oncogene like (avian) gene