Active surveillance for prostate cancer: A systematic review of clinicopathologic variables and biomarkers for risk stratification

Stacy Loeb, Sophie M. Bruinsma, Joseph Nicholson, Alberto Briganti, Tom Pickles, Yoshiyuki Kakehi, Sigrid V. Carlsson, Monique J. Roobol

Research output: Contribution to journalArticle

Abstract

Context Active surveillance (AS) is an important strategy to reduce prostate cancer overtreatment. However, the optimal criteria for eligibility and predictors of progression while on AS are debated. Objective To review primary data on markers, genetic factors, and risk stratification for patient selection and predictors of progression during AS. Evidence acquisition Electronic searches were conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2014 for original articles on biomarkers and risk stratification for AS. Evidence synthesis Patient factors associated with AS outcomes in some studies include age, race, and family history. Multiple studies provide consistent evidence that a lower percentage of free prostate-specific antigen (PSA), a higher Prostate Health Index (PHI), a higher PSA density (PSAD), and greater biopsy core involvement at baseline predict a greater risk of progression. During follow-up, serial measurements of PHI and PSAD, as well as repeat biopsy results, predict later biopsy progression. While some studies have suggested a univariate relationship between urinary prostate cancer antigen 3 (PCA3) and transmembrane protease, serine 2-v-ets avian erythroblastosis virus E26 oncogene homolog gene fusion (TMPRSS2:ERG) with adverse biopsy features, these markers have not been consistently shown to independently predict AS outcomes. No conclusive data support the use of genetic tests in AS. Limitations of these studies include heterogeneous definitions of progression and limited follow-up. Conclusions There is a growing body of literature on patient characteristics, biopsy features, and biomarkers with potential utility in AS. More data are needed on practical applications such as combining these tests into multivariable clinical algorithms and long-term outcomes to further improve AS in the future. Patient summary Several PSA-based tests (free PSA, PHI, PSAD) and the extent of cancer on biopsy can help to stratify the risk of progression during active surveillance. Investigation of several other markers is under way.

Original languageEnglish
Pages (from-to)619-626
Number of pages8
JournalEuropean Urology
Volume67
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Prostatic Neoplasms
Biomarkers
Prostate-Specific Antigen
Biopsy
Prostate
Health
Alpharetrovirus
Gene Fusion
Serine Proteases
Genetic Markers
Oncogenes
PubMed
Patient Selection
Antigens
Neoplasms

Keywords

  • Active surveillance
  • Genetic markers
  • Nomogram
  • Prostate cancer
  • PSA
  • Risk stratification
  • Treatment

ASJC Scopus subject areas

  • Urology

Cite this

Active surveillance for prostate cancer : A systematic review of clinicopathologic variables and biomarkers for risk stratification. / Loeb, Stacy; Bruinsma, Sophie M.; Nicholson, Joseph; Briganti, Alberto; Pickles, Tom; Kakehi, Yoshiyuki; Carlsson, Sigrid V.; Roobol, Monique J.

In: European Urology, Vol. 67, No. 4, 01.04.2015, p. 619-626.

Research output: Contribution to journalArticle

Loeb, Stacy ; Bruinsma, Sophie M. ; Nicholson, Joseph ; Briganti, Alberto ; Pickles, Tom ; Kakehi, Yoshiyuki ; Carlsson, Sigrid V. ; Roobol, Monique J. / Active surveillance for prostate cancer : A systematic review of clinicopathologic variables and biomarkers for risk stratification. In: European Urology. 2015 ; Vol. 67, No. 4. pp. 619-626.
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abstract = "Context Active surveillance (AS) is an important strategy to reduce prostate cancer overtreatment. However, the optimal criteria for eligibility and predictors of progression while on AS are debated. Objective To review primary data on markers, genetic factors, and risk stratification for patient selection and predictors of progression during AS. Evidence acquisition Electronic searches were conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2014 for original articles on biomarkers and risk stratification for AS. Evidence synthesis Patient factors associated with AS outcomes in some studies include age, race, and family history. Multiple studies provide consistent evidence that a lower percentage of free prostate-specific antigen (PSA), a higher Prostate Health Index (PHI), a higher PSA density (PSAD), and greater biopsy core involvement at baseline predict a greater risk of progression. During follow-up, serial measurements of PHI and PSAD, as well as repeat biopsy results, predict later biopsy progression. While some studies have suggested a univariate relationship between urinary prostate cancer antigen 3 (PCA3) and transmembrane protease, serine 2-v-ets avian erythroblastosis virus E26 oncogene homolog gene fusion (TMPRSS2:ERG) with adverse biopsy features, these markers have not been consistently shown to independently predict AS outcomes. No conclusive data support the use of genetic tests in AS. Limitations of these studies include heterogeneous definitions of progression and limited follow-up. Conclusions There is a growing body of literature on patient characteristics, biopsy features, and biomarkers with potential utility in AS. More data are needed on practical applications such as combining these tests into multivariable clinical algorithms and long-term outcomes to further improve AS in the future. Patient summary Several PSA-based tests (free PSA, PHI, PSAD) and the extent of cancer on biopsy can help to stratify the risk of progression during active surveillance. Investigation of several other markers is under way.",
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N2 - Context Active surveillance (AS) is an important strategy to reduce prostate cancer overtreatment. However, the optimal criteria for eligibility and predictors of progression while on AS are debated. Objective To review primary data on markers, genetic factors, and risk stratification for patient selection and predictors of progression during AS. Evidence acquisition Electronic searches were conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2014 for original articles on biomarkers and risk stratification for AS. Evidence synthesis Patient factors associated with AS outcomes in some studies include age, race, and family history. Multiple studies provide consistent evidence that a lower percentage of free prostate-specific antigen (PSA), a higher Prostate Health Index (PHI), a higher PSA density (PSAD), and greater biopsy core involvement at baseline predict a greater risk of progression. During follow-up, serial measurements of PHI and PSAD, as well as repeat biopsy results, predict later biopsy progression. While some studies have suggested a univariate relationship between urinary prostate cancer antigen 3 (PCA3) and transmembrane protease, serine 2-v-ets avian erythroblastosis virus E26 oncogene homolog gene fusion (TMPRSS2:ERG) with adverse biopsy features, these markers have not been consistently shown to independently predict AS outcomes. No conclusive data support the use of genetic tests in AS. Limitations of these studies include heterogeneous definitions of progression and limited follow-up. Conclusions There is a growing body of literature on patient characteristics, biopsy features, and biomarkers with potential utility in AS. More data are needed on practical applications such as combining these tests into multivariable clinical algorithms and long-term outcomes to further improve AS in the future. Patient summary Several PSA-based tests (free PSA, PHI, PSAD) and the extent of cancer on biopsy can help to stratify the risk of progression during active surveillance. Investigation of several other markers is under way.

AB - Context Active surveillance (AS) is an important strategy to reduce prostate cancer overtreatment. However, the optimal criteria for eligibility and predictors of progression while on AS are debated. Objective To review primary data on markers, genetic factors, and risk stratification for patient selection and predictors of progression during AS. Evidence acquisition Electronic searches were conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2014 for original articles on biomarkers and risk stratification for AS. Evidence synthesis Patient factors associated with AS outcomes in some studies include age, race, and family history. Multiple studies provide consistent evidence that a lower percentage of free prostate-specific antigen (PSA), a higher Prostate Health Index (PHI), a higher PSA density (PSAD), and greater biopsy core involvement at baseline predict a greater risk of progression. During follow-up, serial measurements of PHI and PSAD, as well as repeat biopsy results, predict later biopsy progression. While some studies have suggested a univariate relationship between urinary prostate cancer antigen 3 (PCA3) and transmembrane protease, serine 2-v-ets avian erythroblastosis virus E26 oncogene homolog gene fusion (TMPRSS2:ERG) with adverse biopsy features, these markers have not been consistently shown to independently predict AS outcomes. No conclusive data support the use of genetic tests in AS. Limitations of these studies include heterogeneous definitions of progression and limited follow-up. Conclusions There is a growing body of literature on patient characteristics, biopsy features, and biomarkers with potential utility in AS. More data are needed on practical applications such as combining these tests into multivariable clinical algorithms and long-term outcomes to further improve AS in the future. Patient summary Several PSA-based tests (free PSA, PHI, PSAD) and the extent of cancer on biopsy can help to stratify the risk of progression during active surveillance. Investigation of several other markers is under way.

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