Prostate cancer (PCa) remains an increasingly common malignancy worldwide. The optimal management of clinically localized, early-stage disease remains unknown, and profound quality of life issues surround PCa interventions.
Objective
To systematically summarize the current literature on the management of low-risk PCa with active surveillance (AS), with a focus on patient selection, outcomes, and future research needs.
Evidence acquisition
A comprehensive search of the PubMed and Embase databases from 1980 to 2011 was performed to identify studies pertaining to AS for PCa. The search terms used included prostate cancer and active surveillance or conservative management or watchful waiting or expectant management. Selected studies for outcomes analysis had to provide a comprehensive description of entry characteristics, criteria for surveillance, and indicators for further intervention.
Evidence synthesis
Data from seven large AS series were reviewed. Inclusion criteria for surveillance vary among studies, and eligibility therefore varies considerably (4–82%). PCa-specific mortality remains low (0–1%), with the longest published median follow-up being 6.8 yr. Up to one-third of patients receive secondary therapy after a median of about 2.5 yr of surveillance. Surveillance protocols and triggers for intervention vary among institutions. Most patients are treated for histologic reclassification (27–100%) or prostate-specific antigen doubling time <3 yr (13–48%), while 7–13% are treated with no evidence of progression. Repeat prostate biopsy with a minimum of 12 cores appears to be important for monitoring patients for changes in tumor histology over time.
Conclusions
AS for PCa offers an opportunity to limit intervention to patients who will likely benefit the most from radical treatment. This approach confers a low risk of disease-specific mortality in the short to intermediate term. An early, confirmatory biopsy is essential for limiting the risk of underestimating tumor grade and amount.
Introduction
Prostate cancer (PCa) continues to pose significant health care challenges worldwide. Estimates show that it remains the number one cancer diagnosis in North American and European men, with age-adjusted incidence rates of 85.6 and 59.3 per 100 000, respectively [1]. PCa treatment effects, however, can be profound and prolonged. Although published single-institution series describe varying functional outcomes with PCa treatment, findings from larger, diverse data sets relate substantial rates of urinary and sexual dysfunction [2]. Many contemporary prostate tumors are estimated to have a protracted natural history and pose little threat to patients during their lifetime. Despite this evidence, the majority of men with newly diagnosed PCa undergo some form of aggressive treatment regardless of risk, and the changing landscape of PCa has led to concerns regarding overdiagnosis and overtreatment. Active surveillance (AS) and organ-sparing focal therapies have emerged as alternative treatment options for men with early-stage disease and continue to be intensely investigated.
The American Urological Association, European Association of Urology, and the National Comprehensive Care Network have all published guidelines for the treatment of localized PCa that include AS [3], [4], [5]. In addition, the US National Institutes of Health recently issued a consensus statement on AS for managing men with localized PCa [6]. Despite these guidelines, many uncertainties remain, including the long-term all-cause and disease-specific mortality, optimal patient selection, surveillance strategies, and triggers for intervention. The goal of this review is to summarize the current state of the literature while discussing ongoing and future needs with unanswered questions. Updates from major published series with longer follow-up periods are reviewed, with a focus on expanding eligibility, surveillance strategies, and triggers for intervention.
Section snippets
Evidence acquisition
A systematic review of the electronic databases PubMed and Embase from 1980 to 2011 was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement guidelines and limited to the English language (Fig. 1). The search terms used included prostate cancer and active surveillance or conservative management or watchful waiting or expectant management. Selected studies for outcomes analysis had to provide a comprehensive description of the demographic and
Criteria for active surveillance
Criteria for AS set forth from published series are shown in Table 1 [7], [8], [9], [10], [11], [12], [13], [14], [15]. First described in 1994, and then updated in 2004, the Epstein criteria integrate biopsy criteria with clinical data to identify potentially low-risk tumors and are among the most commonly used methods to identify low-risk disease [16], [17]. Characteristics of “insignificant” tumors include clinical stage T1; Gleason pattern ≤3 in the biopsy specimen (ie, no Gleason pattern
Conclusions
As AS series continue to mature, data show that disease-specific mortality remains low, with moderate rates of intervention over the first few years. Decisions regarding management of localized PCa, including AS, should be made with an individualized approach after careful risk assessment. Men should be counseled upfront on the need for ongoing surveillance as well as the definitions of progression that may lead to a recommendation for treatment. A confirmatory biopsy within the first year is
