title: Insulin-like growth factors (IGFs) and IGF-binding proteins in active monitoring of localized prostate cancer: a population-based observational study.
abstract: OBJECTIVE
  Active monitoring of prostate cancer requires the selection of low-risk cancers and subsequent identification of disease progression. Our objective was to determine whether serum insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-2 or IGFBP-3 at diagnosis (potential biomarkers of prognosis), and repeated measures of IGFBP-2 (potential biomarker of tumour growth), were associated with annual change in PSA and PSA doubling time (PSADT), proxies for disease progression.
  
  
  METHODS
  We investigated associations of circulating IGFs and IGFBPs with PSA measures using multilevel models, in 909 men (recruited between 1999 and 2009) with PSA-detected clinically localized prostate cancer undergoing active monitoring in the United Kingdom. Each man had an average of 14 measurements of PSA during a mean of 4-year follow-up.
  
  
  RESULTS
  IGF-I, IGF-II, IGFBP-2, and IGFBP-3 were not associated with baseline PSA. There was weak evidence that IGF-I at diagnosis was positively associated with a rapid post-diagnosis PSADT (≤4 years vs. >4 years): OR 1.34 (95 % CI 0.98, 1.81) per SD increase in IGF-I. IGFBP-2 increased by 2.1 % (95 % CI 1.4, 2.8) per year between 50 and 70 years, with no association between serial IGFBP-2 levels and PSADT. There was no evidence that serum IGF-II, IGFBP-2, or IGFBP-3, or post-diagnosis IGFBP-2, were associated with PSA kinetics in men with PSA-detected localized prostate cancer.
  
  
  CONCLUSIONS
  The weak association of IGF-I with PSADT requires replication in larger datasets, and more definitive evidence will be provided on the maturity of long-term active monitoring cohorts with relevant clinical outcomes (metastasis and prostate cancer mortality).
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, UK. mari-anne.rowlands@bristol.ac.uk
authors.forename: Mari-Anne
authors.initials: MA
authors.lastname: Rowlands
authors.forename: Kate
authors.initials: K
authors.lastname: Tilling
authors.forename: Jeff M P
authors.initials: JM
authors.lastname: Holly
authors.forename: Chris
authors.initials: C
authors.lastname: Metcalfe
authors.forename: David
authors.initials: D
authors.lastname: Gunnell
authors.forename: Athene
authors.initials: A
authors.lastname: Lane
authors.forename: Michael
authors.initials: M
authors.lastname: Davis
authors.forename: Jenny
authors.initials: J
authors.lastname: Donovan
authors.forename: Freddie
authors.initials: F
authors.lastname: Hamdy
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D005500:Follow-Up Studies; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis / Q000097:blood / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods*; D019370:Observation; D011153:Population; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D013002:Somatomedins / Q000032:analysis / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D017430:Prostate-Specific Antigen