The Evolution of Active Surveillance for Prostate Cancer

Abstract

The aimof active surveillance for localised prostate cancer is to offer timely treatment to[6_TD$DIFF] those men who need it while avoiding the harms of unnecessary treatment in those with indolent disease. The safety of active surveillance has been documented in relatively large, mature cohort studies. For example, among the Toronto cohort of 993men followed for up to 19 yr, more than half have avoided treatment and just 2.8% have developed metastatic disease [1]. Since active surveillance was first described [2] there has been uncertainty about how it should be carried out. Repeat transrectal ultrasound (TRUS) biopsy has been widely regarded as part of the standard approach to monitoring men with untreated localised disease, but the limitations of TRUS biopsy arewell known: it is painful, can lead to severe sepsis, and is prone to significant sampling error. In this issue of European Urology, Bokhorst and colleagues [3] add a further item to the list of problems associated with TRUS biopsy: lack of compliance. The Prostate Cancer Research International: Active Surveillance (PRIAS) protocol recommends biopsy after 1, 4, 7, and 10 yr, andwhen amanhas a prostate-specific antigen (PSA) doubling time of <10 yr. However, according to [7_TD$DIFF] data from more than 4000 men, only approximately 30% of them underwent all repeat biopsies specified by the protocol. This is not surprising given that thesemenare likely to have already experienced short-term biopsy-related side effects (pain, bleeding, fever), with a few having more serious complications such as hospital admission for infection. A study of men in the UK PROTECT study suggested that 20% ofmen asked in the firstmonth after biopsywould consider a repeat biopsy a major or moderate problem [4]. While compliance with PSA monitoring was high in the PRIAS study (91%), it is well documented that PSA dynamics are not a reliable trigger for intervention in men on active surveillance when compared to an annual repeat biopsy strategy [5]. There is therefore a clear need for a noninvasive and accurate way to monitor men on active surveillance. Multiparametric magnetic resonance imaging (mpMRI) is certainly less invasive than TRUS biopsy and might also provide a more accurate assessment of disease progression. Incorporation of mpMRI into active surveillance protocols could both safely reduce the need for repeat biopsies and improve the accuracy of the biopsies that are performed. For men on active surveillance who have negative mpMRI or MRI concordant with the initial biopsy, there is little utility in repeating a standard TRUS biopsy [6]. In one series, 78% of men on active surveillance could have avoided a biopsy according to MRI criteria [7]. Another group reported data suggesting that [8_TD$DIFF]radiological stability on MRI is associated with Gleason grade stability on repeat targeted biopsy [8]. For men on surveillance with suspicious MRI findings, MRI could be used to improve the detection of significant disease on repeat biopsy. In a cohort study of 1003 men, MRI-targeted biopsy detected 30% more high-risk cancers than standard biopsy (173 vs 122) [9]. A [9_TD$DIFF] further study confirmed this finding in 1140 men randomised to MRItargeted biopsy or standard biopsy [10]. There are of course limitations toMRI: somemenwill not be able to have full mpMRI (eg, no contrast because of reduced renal function or implanted cardiac or neurostimulatory devices). The cost of an image-based active surveillance programme will[1_TD$DIFF] need to be borne in mind, and it is likely that a risk-stratified approach will give the greatest benefit for the lowest cost. Men with a visible lesion on MRI might need annual imaging, at least initially, whereas those with negative MRI could be imaged less E U RO P E AN URO L OG Y 6 8 ( 2 0 1 5 ) 8 2 2 – 8 2 3