Elsevier

European Urology

Volume 63, Issue 4, April 2013, Pages 597-603
European Urology

Platinum Priority – Prostate Cancer
Editorial by Markus Graefen and Thorsten Schlomm on pp. 604–605 of this issue
Active Surveillance for Low-Risk Prostate Cancer Worldwide: The PRIAS Study

https://doi.org/10.1016/j.eururo.2012.11.005Get rights and content

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).

Introduction

Prostate cancer (PCa) affects many men worldwide, with >900 000 diagnoses and >258 000 deaths from the disease in 2008 [1]. Studies on PCa screening have shown a positive effect of screening, with a reduction of disease-specific mortality of up to 21–30% [2], [3]. However, because of the increasing use of prostate-specific antigen (PSA) testing over the last two to three decades, the proportion of low-risk tumors for which early detection and treatment will not change prognosis has been rising [4]. Treatment of these so-called overdiagnosed cases will inevitably lead to overtreatment and its potential side effects, thereby negatively affecting the patients’ quality of life.

Over the last decade, active surveillance (AS) has evolved as an alternative to radical treatment of low-risk PCa. AS focuses on the prevention of overtreatment by selecting patients with low-risk disease features and strictly monitoring them over time to recognize any potential risk reclassification that would justify deferred radical treatment, still with curative intent. Several AS studies have been initiated worldwide that show quite similar and favorable outcomes. However, follow-up in the majority of cohorts is still short, and prospective validation of criteria for selecting low-risk disease therefore is still lacking. In 2006, the Prostate Cancer Research International: Active Surveillance (PRIAS) study was initiated to counteract overtreatment and contribute to prospective data collection. PRIAS aims to reflect daily practice by collecting data from affiliated centers worldwide using an Internet-based decision tool and the PRIAS protocol. The first data on this study were reported on the first 500 patients in 2009 [5]. This study represents an update of our experience with nearly 2500 patients.

Section snippets

Methods

The PRIAS study started including patients in December 2006, and recruitment is ongoing. More than 100 medical centers in 17 countries worldwide contribute to the collection of data using an Internet-based tool for entering information on patients’ baseline and follow-up characteristics (www.prias-project.org). This report was updated until May 2012. Eligible patients fulfill the PRIAS inclusion criteria for low-risk PCa: clinical stage T1C/T2, PSA ≤10 ng/ml, PSA density (PSA-D) <0.2 ng/ml per

Results

Up to May 2012, 2494 men (median age: 65.8 yr) meeting all inclusion criteria were included in PRIAS. The distribution across participating countries is shown in Table 1. Median follow-up for the cohort was 1.6 yr (25th and 75th percentile [25–75p]: 1.0–2.8 yr). Baseline characteristics of the study group are shown in Table 2.

A total of 1858 repeat biopsies were performed in 1480 men. A first repeat biopsy was done in 1480 patients (79.7%), 308 patients (16.6%) underwent a second repeat biopsy,

Discussion

We report updated results from the largest prospective AS cohort for low-risk PCa that acquires data from >100 medical centers worldwide. Our analyses show that in addition to age and PSA at diagnosis, both PSA-D and the number of positive cores at diagnosis (two compared with one) are important predictors for reclassification at repeat biopsy. The latter two predictors are also shown to be associated with the likelihood of switching to active therapy during follow-up. The majority of patients

Conclusions

In an era of widespread availability of PSA-based screening, AS is of growing interest as an alternative to treatment of low-risk PCa. PRIAS is the largest observational prospective study evaluating AS worldwide and our data support AS as a feasible strategy to reduce overtreatment, at least in the short term, without compromising curability.

Clinical characteristics and PSA kinetics can be used to predict who will be reclassified to higher risk during follow-up and who is more likely to switch

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