Prostate cancer (PCa) is the second most frequently diagnosed cancer in males worldwide, and the incidence of PCa in Korean men is increasing [1,2]. With the onset of widespread prostate-specific antigen (PSA) testing, resulting in earlier detection of low-risk PCa, the incidence of clinically insignificant PCa has increased proportionately. The changing landscape of PCa has led to concerns regarding overdiagnosis and overtreatment.

Active surveillance (AS) is different from watchful waiting or delayed treatment in that active treatment will be initiated if disease progression becomes apparent at follow-up [3]. In recent years, AS has been more frequently offered as treatment for low-risk PCa [4,5], but this is not the case in Korea.

This study was conducted to describe our early experience with AS.

Overall, the mean age of the patients was 68 years (range, 55-80 years), the mean PSA was 7.38 ng/mL (range, 2.37-10.00 ng/mL), the mean prostate volume was 44.8 mL (range, 20.0-120.0 mL), the mean Gleason score was 4.97 (range, 3-6), the mean PSA density (PSAD) was 0.14 ng/mL (range, 0.05-0.5 ng/mL), and the mean PSA DT was 5.16 years. All of the patients had favorable risk. The mean follow-up duration was 32 months (range, 12-46 months) (Table 2).

In the first year of follow-up, repeat biopsies were performed in 25 patients (71.4%) (13 patients, negative for cancer; 7 patients, Gleason score of 6 without progression; 5 patients, progression). All five patients with progression had a PSA DT of more than 3 years. Three of the five patients whose cancers progressed underwent radical prostatectomy, whereas the other patients requested a transfer to another hospital of their choice.

In the third year, repeat biopsies were performed in five patients (two patients, negative for cancer; one patient, Gleason score of 6 without progression; two patients, progression, treated with radical prostatectomy). Of the two patients with progression, one had a PSA DT of more than 3 years, whereas the other patient had a PSA DT of less than 3 years.

Before the scheduled first-year follow-up visit, three patients were lost to follow-up, whereas seven patients discontinued AS because of increased anxiety. Of these seven patients, four underwent radical prostatectomy, whereas the remaining three patients were treated with antiandrogens based on their age and/or preference (Fig. 1).

Overall, eight patients had a PSA DT of less than 3 years and underwent prostate biopsy earlier. Only one of these patients had cancer progression. Of the seven patients with progression, six (85.7%) had a PSA DT of more than 3 years. and one (14.3%) had a PSA DT of less than 3 years (Table 3). Seventeen patients (48.6%) discontinued AS, for several reasons (Table 4). The mean PSA DT was 7.54 years in the seven patients (28%) whose cancer progressed. Five patients with cancer progression underwent radical prostatectomy (Table 5), four of whom had organ-confined disease and one of whom had extracapsular extension.

In the current PSA era, most patients with an initial diagnosis of localized PCa are considered to be the most likely to achieve a cure. Current treatment options for patients with localized PCa vary-radical prostatectomy, radiotherapy, cryotherapy, androgen ablation therapy, and AS [14].

Since first being introduced in 2002, AS-the concept of which is to cure clinically significant PCa prior to the development of advanced disease-is now an accepted treatment strategy for patients with PCa [4,6]. However, AS is still underused in the United States and is rarely used in Korea [15]. Patients and/or their physicians appear to want to treat PCa once it is diagnosed [6]. In our study, the 10 patients (28.6%) who discontinued AS did not have cancer progression and had a sufficient understanding of AS before it was initiated.

AS may reduce the risk of overtreatment of clinically insignificant PCa, but the individual risk of disease progression is difficult to determine. The first attempt to identify potentially low-risk PCa was described by Epstein et al. [16,17]. Their description focused on disease with clinical stage T1, a Gleason pattern score ≤3, a PSAD ≤0.1 ng/mL/g, two or fewer positive cores, and no cores with >50% involvement. For contemporary AS protocols, most clinicians incorporate the criteria of a low Gleason score (≤6), a low clinical stage (≤T2a), and low PSA values (≤10 ng/mL) with estimates of tumor volume from the biopsy when selecting patients [18]. We also used a similar but stricter criteria to select patients: clinical stage (≤T1c), one positive core (minimum of 12 cores taken), and negative imaging result. Most patients with low-risk PCa have normal ultrasonographic findings. MRI offers advantages over other imaging techniques for the detection of PCa [10]. Recently, MRI with various imaging techniques has improved tumor detection [19,20]. We think that a tumor undetected by MRI may belong to a more favorable risk group.

PSA kinetics have generally been used to predict disease progression. However, the PSA values over time that can predict disease progression during AS remain unknown [18]. Klotz et al. [7], the Johns Hopkins group [21], and the University of California San Francisco cohort [22] focused on PSA kinetics to determine the triggers indicating that AS should be discontinued. However, no correlations were found between the PSA DT and adverse pathologic findings from the surveillance biopsy. In our study, the PSA DT was not associated with cancer progression on biopsy. The eight patients (22.8%) who had a PSA DT of <3 years underwent biopsy earlier, but only one patient had cancer progression. Most patients who had a longer PSA DT did not experience cancer progression during AS. Before a patient decides to undergo definitive intervention, we believe that they should first elect to have a repeat biopsy and be reclassified.

The objective endpoint in an AS series is the number of patients remaining on surveillance after a specified time interval [18]. Several studies that have described the incidence of those who received active treatment during AS report that it ranges from 11% to 32% [7,8,11,23-25]. In our study, 17 patients (48.6%) discontinued AS for several reasons. However, only five patients (14.3%) ultimately received radical prostatectomy after progression. This fact is noteworthy. Patients in Korea want to be treated even if, based on the Epstein criteria, they have clinically insignificant PCa [26,27]. This is partly because of the health insurance system.

Kakehi et al. [9] demonstrated that, given the low mortality from PCa in Asian patients compared with Western patients, AS is a more appealing option for Asians. However, in our study, Korean PCa progression rates appear to be higher than those of other western institutions despite our implementation of stricter patient selection criteria. According to another study conducted in Korea, most patients with low-risk PCa detected on multicore prostate biopsy actually had pathologically upgraded or upstaged disease after examination of the radical prostatectomy specimen [28,29]. We think that AS is a reasonable option for low-risk PCa. However, this strategy is difficult to implement in Korea. In order to carry out AS more safely, optimal patient selection and accurate monitoring using new biomarkers and imaging tools are needed.

This study was limited by its small sample size and short follow-up period. Hence, a statistical analysis was not possible. Additional studies are needed to confirm the nature of low-risk PCa in Korea and to define the appropriate criteria for determining patient selection and cancer progression for AS.

PSA DT did not correlate with the progression of PCa, which suggests that regular biopsies should still be performed while monitoring for cancer progression. Interestingly, progression of PCa during AS resulted in the dissolution of the patient-doctor relationship and resulted in the patients transferring to another hospital. AS is a treatment option for low-risk PCa patients, but is a strategy that is difficult to implement in Korea.