Also initiated in 1995 and first reporting outcomes in 2002 [24], the Sunnybrook experience provides a substantial volume of information regarding the longer-term outcomes of AS. In contrast to the JHU program, inclusion in AS at Sunnybrook has been more permissive. Prior to 2000, patients with Gleason score ≤3 + 4 and serum PSA ≤15 ng/ml were eligible for AS. Since 2000 those criteria have been modified to permit AS for GS ≤3 + 4 and PSA 10–20 ng/ml only in men with life expectancy less than 10 years (Table 18.2). Monitoring at Sunnybrook has consisted of PSA testing every 3–6 months, initial confirmatory biopsy within 1 year of diagnosis, and subsequent biopsies every 3–4 years. Intervention is recommended upon Gleason score upgrading, and, prior to 2008, in cases of PSA doubling time (PSADT) less than 3 years. Based on evidence that PSA kinetics are not reliable predictors of reclassification [35, 36], the program has since considered short PSADT an indicator for further evaluation rather than immediate intervention.

Last reported in 2015, outcomes from Sunnybrook are based on 993 men with a median follow-up of 6.4 years; 206 men were followed for more than 10 years and 50 men for more than 15 years [3]. Notably, 21% of the cohort had intermediate-risk cancer, including 13% with Gleason score ≥7. The cumulative incidence of treatment was 36% at 10 years and 45% at 15 years. During follow-up, 28 men (2.8%) developed metastatic disease , and 15 men (1.5%) died of PCa. Prostate cancer-specific survival was 98.1% at 10 years and 94.3% at 15 years.

The AS experience in Göteborg differs from JHU and Sunnybrook most notably in how the cohort was derived. As reported in 2016 [25], this study population was composed of men diagnosed with PCa based on the Göteborg screening trial, which has been described in detail previously [37]. Importantly, management with AS was not determined based on strict inclusion criteria, but rather the use of AS was classified retrospectively in men with very low-, low-, and intermediate-risk disease who did not undergo curative treatment within 6 months of diagnosis. Similarly, the monitoring protocol was not prospectively defined, but surveillance has generally included PSA testing every 3–6 months. Early rebiopsy (≤12 months) was not standard in the cohort but was typically performed in men with limited cancer volume (<2 mm) at diagnosis to confirm suitability for AS. Additional surveillance biopsies were generally performed every 2–3 years in the absence of other worrisome findings (Table 18.3).

Ultimately, the 474 patient cohorts captured a relatively wide distribution of baseline risk categorization, as it was composed of 51% VLR cancers, 27% LR cancers, and 22% intermediate-risk cancers. Median overall follow-up was 8.0 years, with 181 men followed for more than 10 years and 31 for more than 15 years. The 10- and 15-year rates of treatment were 53% and 66%, respectively. Metastasis-free survival was 99% at 10 years and 93% at 15 years. A total of six men died of PCa, with associated cancer-specific survival rates of 99.5% at 10 years and 96% at 15 years. Notably, there were no deaths among men with very low-risk prostate cancer.

The PRIAS study was initiated in 2006 and represents a departure from the conventional, single-institution approach to AS [38]. In contrast, PRIAS includes participants from academic, nonacademic, and private practices derived from over 150 centers across 18 countries. Patient data are prospectively entered through the PRIAS website, allowing for efficient provision of recommendations and data collection across several sites. Initial patient selection criteria included clinical stage ≤T2c, PSA ≤10 ng/ml, PSAD <0.20 ng/ml/cc, Gleason score ≤6, ≤2 positive biopsy cores, and fitness for curative treatment (Table 18.4). In recent years, these criteria have been adapted to include select Gleason score 3 + 4 = 7 patients and to accommodate changes in practice secondary to the use of saturation or magnetic resonance imaging (MRI)-guided biopsies [26]. The initial 2 years of follow-up include PSA testing every 3 months and DRE every 6 months, and subsequent monitoring includes PSA testing every 6 months and DRE every 1 year. Surveillance biopsies are scheduled at years 1, 4, 7, and 10 from diagnosis; additional interval biopsies are recommended if PSADT is <10 years. Active treatment is recommended upon detection of Gleason score >6, more than two positive biopsy cores, or clinical stage >T2.

As a relatively young study with an innovative, online approach for widely capturing data, PRIAS has reported on 5302 men, of which 3379 underwent at least one surveillance biopsy and 622 were followed for >5 years. At 5 and 10 years of follow-up, 48% and 27% of the cohort remained on AS, respectively. During follow-up, 30 men underwent biochemical recurrence (BCR) after prostatectomy or radiotherapy, 10 developed local recurrences, 8 developed metastatic disease, and 1 man died of PCa. Given the low event rate and limited follow-up, the authors reported a composite endpoint including BCR, local recurrence, metastasis, and PCa death. Cumulative incidence of this outcome was 2% at 5 years and 6% at 10 years following diagnosis.

UCSF has prospectively collected clinical data in men diagnosed with PCa who did not undergo active treatment for at least 6 months for many years [27]. This active surveillance cohort has evolved with time in terms of patient inclusion and monitoring criteria. As of 2015, strict inclusion criteria included serum PSA ≤10 ng/ml, clinical stage T1/2, biopsy Gleason score ≤6, ≤33% of biopsy cores positive, and ≤50% cancer involvement of any core (Table 18.5). Recommended monitoring has included PSA testing every 3 months, transrectal ultrasound (TRUS) every 6 months, and an initial confirmatory biopsy within 12 months of diagnosis. Subsequent prostate biopsies have been recommended every 1–2 years according to clinical risk. Indications for treatment include biopsy, Cancer of the Prostate Risk Assessment (CAPRA) risk, or clinical stage reclassification.

Clinical data were reported in 2015. A total of 810 men consented to study inclusion and had accrued at least 6 months of follow-up, of which 556 (69%) met inclusion criteria. Over a median follow-up of 60 months, including over 200 men with at least 7.5 years of follow-up, the authors observed metastatic disease in only 1 man (0.12%) and prostate cancer death in none. Five-year treatment-free survival was 60%. Additional time-specific outcomes were not reported.

In 2002, the Royal Marsden Hospital in the United Kingdom (UK) began prospectively collecting data on men managed with AS [39]. This program differs from others in that it selectively excludes very young men and the elderly by restricting eligibility to men aged 50–80 years. Enrollment criteria include clinical stage T1/T2, PSA <15 ng/ml, Gleason score ≤6, and no more than 50% of overall biopsy cores positive (Table 18.6) [28]. Men who presented with Gleason score 3 + 4 were in some cases also enrolled if they were older than age 65. The inclusion criteria for Royal Marsden are relatively permissive in some regards; for example, there is not a specific threshold for exclusion based on elevated PSAD or high involvement of cancer within a positive biopsy core. During surveillance, PSA and DRE are performed every 3 months in year 1, every 4 months in year 2, and every 6 months thereafter; biopsies are performed approximately every 2 years. Intervention for treatment is recommended if the PSA velocity (PSAV) exceeds 1 ng/ml per year or if adverse histology is detected on repeat biopsy, defined as Gleason score ≥4 + 3 or the presence of cancer in more than 50% of biopsy cores obtained.

As of 2013, the Royal Marsden experience included 471 men (median age 66 years) managed with AS for a median follow-up time of 5.7 years. Of these, 383 (81.3%) were classified as low risk, while the remaining 88 (18.7%) were intermediate risk. Within the cohort, 33 men (7.0%) were diagnosed with Gleason score 3 + 4 disease. Analysis of intermediate-term outcomes from this cohort demonstrated 2- and 5-year treatment-free survival rates of 89% and 70%, respectively. The rate of adverse histology at these same time points was 6% and 22%, respectively. While rates of metastatic disease were not reported, there were two (0.4%) deaths attributed to prostate cancer over the entire follow-up period.

As the concept of active surveillance has taken hold, numerous institutions from around the world have followed suit in reporting their respective experiences. Three additional cohorts have contributed to the literature describing outcomes over the shorter term (median follow-up <5 years).