1. Department of Urology, Erasmus MC, Rotterdam, The Netherlands;2. Prostate Program, Scientific Directorate, Fondazione IRCSS Instituto Nazionale dei Tumori, Milan, Italy;3. Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver, Canada;4. Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan;5. Department of Urology, Helsinki University Central Hospital, Helsinki, Finland;6. Department of Urology, Skåne University Hospital, Malmö, Sweden;g Department of Urology, Amphia Hospital, Breda, The Netherlands;h Department of Urology, Ziekenhuis Groep Twente, Hengelo, The Netherlands;i Department of Urology, St. Anna Hospital, Como, Italy;j Department of Urology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands;k Department of Urology, Polyclinique Les Bleuets, Reims, France;l Department of Urology, Albert Schweitzer Hospital, Dordrecht, The Netherlands;m Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands;n Department of Urology, Admiraal De Ruyter Ziekenhuis, Goes, The Netherlands;o Martini-Klinik, Hamburg, Germany;p Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands
Abstract:
Background
Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing interest as an alternative to radical treatment of low-risk PCa.
Objective
To update our experience in the largest worldwide prospective AS cohort.
Design, setting, and participants
Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤6. PSA was measured every 3–6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification.
Outcome measurements and statistical analysis
Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy–free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time.
Results and limitations
In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS.
Conclusions
Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized.
Trial registration
The current program is registered at the Dutch Trial Register with ID NTR1718 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718).
