Elsevier

European Urology

Volume 55, Issue 6, June 2009, Pages 1321-1332
European Urology

Review – Prostate Cancer
Insignificant Prostate Cancer and Active Surveillance: From Definition to Clinical Implications

https://doi.org/10.1016/j.eururo.2009.02.028Get rights and content

Abstract

Context

Due to early detection strategies, prostate cancer is diagnosed early in its natural history. It remains unclear whether all patients diagnosed with prostate cancer warrant radical treatment or may benefit from delayed intervention following active surveillance.

Objective

A systematic review of active surveillance protocols to investigate the inclusion criteria for active surveillance and the outcome of treatment.

Evidence acquisition

Medline was searched using the following terms: prostate cancer, active surveillance and expectant management for dates up to October 2008. Further studies were chosen on the basis of manual searches of reference lists and review papers.

Evidence synthesis

Numerous studies on active surveillance were identified. The recent inclusion criteria of the studies are rather similar. Keeping the short follow-up of all studies in mind, the majority of men stay on active surveillance, and the percentage of patients receiving active treatment is as high as 35% of all patients. Once a patients requires active treatment, most patients still present with curable prostate cancer. Furthermore, only few deaths due to prostate cancer have occurred.

Conclusions

Active surveillance is an alternative option to immediate treatment of men with presumed insignificant prostate cancer. It seems that criteria used to identify men with low-risk prostate cancer are rather similar, and immediate treatment of men meeting these criteria may result in an unnecessary number of treatments in these highly selected patients. Data from randomised trials comparing active surveillance and active treatment will provide additional insight into outcome and follow-up strategies.

Introduction

Prostate cancer (PCa) is the most frequently diagnosed solid malignant tumour among men in the United States and Western Europe. A significant increase in the diagnoses of men with nonpalpable PCa has occurred since the beginning of the prostate-specific antigen (PSA) testing era in the late 1980s. The lifetime risk of developing PCa in the United States is 1 in 6, and the lifetime risk of death due to metastatic PCa is 1 in 30 [1]. The estimated age-standardised mortality rates for PCa per 100 000 men is 23.2 in Europe in 2006 [2]. However, the natural history of screen-detected PCa remains poorly understood. Autopsy studies have revealed that 50% of men in the age group of 40–49 yr harbour PCa [3]. Eighty percent of these cancers are of low volume (<0.5 cm3), and low grade and can be classified as insignificant according to the so-called Epstein criteria [4], [5].

The advent of PSA testing and modified prostatic biopsy schemes have led to the establishment of overdiagnosis, which is an epidemiologic term and is defined as the diagnosis of cancers which will not be diagnosed clinically during life [6].

Even the introduction of more refined PSA testing (ie, complex PSA, free PSA, ratio of free PSA to total PSA) and PSA kinetics (ie, PSA doubling time [PSA DT] or PSA velocity) have not been able to solve this clinical dilemma [7], [8], [9], [10].

At present, the rate of overdetection of PCa is suggested to be as high as 56% [6], [11]. This has also led to the well-recognised phenomenon called “stage migration,” meaning that today more PCa is detected at earlier stages, potentially reducing cancer-specific mortality [12].

At present, active treatment of newly diagnosed PCa remains the gold standard, even considering earlier detection of PCa [7]. However, no matter what treatment option for localised PCa is chosen, there is always a chance of decreased quality of life once sexual function and urinary function are altered [13]. Using modern risk stratification, certain centres have gained experience to better identify patients with a low risk of PCa progression and have started to use active surveillance with delayed, selective, or curative therapy [14]. Interestingly, only limited numbers of patients under active surveillance require additional treatment. Thus, with short follow-up, it appears that delayed treatment in these highly selected cases does not alter outcome.

The aim of this review is to define insignificant PCa and, subsequently, potential candidates for active surveillance. A critical analysis of the results seen in PCa patients undergoing active surveillance as an alternative treatment option is also performed.

Section snippets

Evidence acquisition

Medline was searched using the following terms: prostate cancer, active surveillance and expectant management for dates up to October 2008. Further studies were chosen on the basis of manual searches of reference lists and review papers and from meetings of the European Association of Urology (EAU) and the American Urological Association (AUA). This approach was chosen because previous work has shown that manual search improves the database search. Since there are only limited reported data on

Insignificant prostate cancer

A critical factor for successful active surveillance is the best possible patient selection. Obviously, patients with an identifiable low risk of progression are most likely to be safely observed and treated only when necessary. Epstein et al introduced prostate biopsy criteria to predict insignificant PCa (Table 1) [5]. These criteria include the following: clinical stage T1c, PSA density <0.15 ng/ml, no Gleason pattern 4 or 5, fewer than three positive cores, <50% cancer per core [5]. In

Conclusions

In summary, active surveillance is an alternative treatment option to immediate treatment of men with presumed low-risk PCa. It seems that criteria used to identify men with low risk PCa are rather similar, and immediate treatment of men meeting these criteria may result in an unnecessary number of treatments in these highly selected patients. However, today the criteria to predict low-risk, organ-confined PCa are not perfect, and certain number of patients that warrant immediate treatment may

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