title: Compliance Rates with the Prostate Cancer Research International Active Surveillance (PRIAS) Protocol and Disease Reclassification in Noncompliers.
abstract: BACKGROUND
  Men with prostate cancer on active surveillance (AS) are advised to follow strict follow-up schedules and switch to definitive treatment on risk reclassification. However, some men might not adhere to these strict protocols.
  
  
  OBJECTIVE
  To determine the number of noncompliers and disease reclassification rates in men not complying with the follow-up protocol of the Prostate Cancer Research International Active Surveillance (PRIAS) study.
  
  
  METHODS
  A total of 4547 men with low-risk prostate cancer were included and prospectively followed on AS. Men were regularly examined using prostate-specific antigen (PSA), digital rectal examination, and repeat biopsies, and were advised to switch to definitive treatment on disease reclassification (>cT2c, Gleason score > 3+3, >2 cores positive, or PSA doubling time [PSA-DT] 0-3 yr).
  
  
  METHODS
  Rates of men not complying with follow-up visits or a recommendation to discontinue AS are reported. Biopsy outcome (Gleason ≥7 or >2 cores positive) was compared between compliers and noncompliers using Cox proportional hazards analysis.
  
  
  CONCLUSIONS
  The compliance rate for PSA visits was 91%. By contrast, the compliance rate for standard repeat biopsies decreased over time (81%, 60%, 53%, and 33% at 1, 4, 7, and 10 yr after diagnosis, respectively). Yearly repeat biopsies in men with faster rising PSA (PSA-DT 3-10 yr) was low at <30%, although these men had higher upgrading rates at repeat biopsy (25-30% vs 16%). PSA-DT of 0-3 yr was the most common recommendation for discontinuation, but 71% continued on AS. Men with PSA-DT of 0-3 yr were at higher risk of upgrading on repeat biopsy (hazard ratio 2.02, 95% confidence interval 1.36-3.00) compared to men without fast rising PSA.
  
  
  CONCLUSIONS
  Some men and their physicians do not comply with AS follow-up protocols. In particular, yearly repeat biopsies in men with fast rising PSA are often ignored, as is the recommendation to discontinue AS because of very fast rising PSA. Although these men are at greater risk of higher Gleason scores on repeat biopsy, the majority still exhibit favorable tumor characteristics. Fast rising PSA should therefore not trigger a recommendation to receive active treatment, but should rather serve as a criterion for stricter follow-up. In addition, we should aim to find ways of safely reducing the number of biopsies to increase adherence to AS protocols.
  
  
  RESULTS
  We looked at compliance with an active surveillance protocol for low-risk prostate cancer in a large active surveillance study. We observed reluctance to undergo yearly biopsies because of fast rising prostate-specific antigen, despite a higher risk of disease progression. Further research should aim to safely reduce the number of repeat biopsies in men on active surveillance to increase protocol adherence.
authors.affiliation: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: l.bokhorst@erasmusmc.nl.
authors.forename: Leonard P
authors.initials: LP
authors.lastname: Bokhorst
authors.affiliation: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Arnout R
authors.initials: AR
authors.lastname: Alberts
authors.affiliation: Department of Urology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Rannikko
authors.affiliation: Prostate Cancer Program and Radiation Oncology 1, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Valdagni
authors.affiliation: Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Tom
authors.initials: T
authors.lastname: Pickles
authors.affiliation: Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kakehi
authors.affiliation: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.affiliation: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Roobol
mesh_terms: D000368:Aged; D001706:Biopsy; D002985:Clinical Protocols; D051517:Digital Rectal Examination; D018450:Disease Progression; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010349:Patient Compliance / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms; D012306:Risk; D057832:Watchful Waiting / Q000379:methods*
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Active surveillance; Compliance; Disease progression; Prostate biopsy; Prostate-specific antigen; Prostatic neoplasms