title: Current strategies for monitoring men with localised prostate cancer lack a strong evidence base: observational longitudinal study.
abstract: BACKGROUND
  The UK National Institute for Health and Clinical Excellence (NICE) guidance recommends conservative management of men with 'low-risk' localised prostate cancer, monitoring the disease using prostate-specific antigen (PSA) kinetics and re-biopsy. However, there is little evidence of the changes in PSA level that should alert to the need for clinical re-assessment.
  
  
  METHODS
  This study compares the alerts resulting from PSA kinetics and a novel longitudinal reference range approach, which incorporates age-related changes, during the monitoring of 408 men with localised prostate cancer. Men were monitored by regular PSA tests over a mean of 2.9 years, recording when a man's PSA doubling time fell below 2 years, PSA velocity exceeded 2 ng ml(-1) per year, or when his upper 10% reference range was exceeded.
  
  
  RESULTS
  Prostate-specific antigen doubling time and PSA velocity alerted a high proportion of men initially but became unresponsive to changes with successive tests. Calculating doubling time using recent PSA measurements reduced the decline in response. The reference range method maintained responsiveness to changes in PSA level throughout the monitoring.
  
  
  CONCLUSIONS
  The increasing unresponsiveness of PSA kinetics is a consequence of the underlying regression model. Novel methods are needed for evaluation in cohorts currently being managed by monitoring. Meanwhile, the NICE guidance should be cautious.
authors: Department of Social Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK. chris.metcalfe@bristol.ac.uk
authors: C
authors: C
authors: Metcalfe
authors: K
authors: K
authors: Tilling
authors: M
authors: M
authors: Davis
authors: J A
authors: JA
authors: Lane
authors: R M
authors: RM
authors: Martin
authors: H
authors: H
authors: Kynaston
authors: P
authors: P
authors: Powell
authors: D E
authors: DE
authors: Neal
authors: F
authors: F
authors: Hamdy
authors: J L
authors: JL
authors: Donovan
mesh_terms: D000368:Aged; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood*; D012016:Reference Values
chemical_list: D017430:Prostate-Specific Antigen