title: Timing of curative treatment for prostate cancer: a systematic review.
abstract: BACKGROUND
  Delaying definitive therapy unfavourably affects outcomes in many malignancies. Diagnostic, psychological, and logistical reasons but also active surveillance (AS) strategies can lead to treatment delay, an increase in the interval between the diagnosis and treatment of prostate cancer (PCa).
  
  
  OBJECTIVE
  To review and summarise the current literature on the impact of treatment delay on PCa oncologic outcomes.
  
  
  METHODS
  A comprehensive search of PubMed and Embase databases until 30 September 2012 was performed. Studies comparing pathologic, biochemical recurrence (BCR), and mortality outcomes between patients receiving direct and delayed curative treatment were included. Studies presenting single-arm results following AS were excluded.
  
  
  RESULTS
  Seventeen studies were included: 13 on radical prostatectomy, 3 on radiation therapy, and 1 combined both. A total of 34 517 PCa patients receiving radical local therapy between 1981 and 2009 were described. Some studies included low-risk PCa only; others included a wider spectrum of disease. Four studies found a significant effect of treatment delay on outcomes in multivariate analysis. Two included low-risk patients only, but it was unknown whether AS was applied or repeat biopsy triggered active therapy during AS. The two other studies found a negative effect on BCR rates of 2.5-9 mo delay in higher risk patients (respectively defined as any with T ≥ 2b, prostate-specific antigen >10, Gleason score >6, >34-50% positive cores; or D'Amico intermediate risk-group). All studies were retrospective and nonrandomised. Reasons for delay were not always clear, and time-to-event analyses may be subject to bias.
  
  
  CONCLUSIONS
  Treatment delay of several months or even years does not appear to affect outcomes of men with low-risk PCa. Limited data suggest treatment delay may have an impact on men with non-low-risk PCa. Most AS protocols suggest a confirmatory biopsy to avoid delaying treatment in those who harbour higher risk disease that was initially misclassified.
authors: University Medical Centre Utrecht, Utrecht, The Netherlands; Netherlands Cancer Institute, Amsterdam, The Netherlands. roodvdb@hotmail.com
authors: Roderick C N
authors: RC
authors: van den Bergh
authors: Peter C
authors: PC
authors: Albertsen
authors: Chris H
authors: CH
authors: Bangma
authors: Stephen J
authors: SJ
authors: Freedland
authors: Markus
authors: M
authors: Graefen
authors: Andrew
authors: A
authors: Vickers
authors: Henk G
authors: HG
authors: van der Poel
mesh_terms: D055088:Early Detection of Cancer; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D018579:Patient Selection; D011237:Predictive Value of Tests; D011468:Prostatectomy / Q000009:adverse effects / Q000401:mortality; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome; D057832:Watchful Waiting
keywords: Active surveillance; Delay; Expectant management; Outcomes; Prostate cancer; Radiation therapy; Radical prostatectomy