Background: Surgery and radiotherapy are standard therapies for patients with early-stage prostate cancer (PrCa). However, studies show that patients with low-risk localized PrCa (Gleason 6; Grade Group (GG) 1 and prostate-specific antigen (PSA) <10) could be safely monitored with active surveillance (AS), if intense patient follow up and re-biopsy schedules are utilized. Here, we reviewed clinical outcomes of AS of a program associated with the Niagara Health System (NHS) PrCa diagnostic program, which provides centralized diagnosis, systematic follow up, re-biopsy and multi-disciplinary consultation clinics for all patients in the Niagara region, Ontario, Canada. Methods: After receiving appropriate ethics approval, NHS databases were searched for patients that underwent more than one biopsy of the prostate in the period Jan. 2015 (program inception) to Dec. 2020. Cases were reviewed for clinical stage, biopsy results and treatment record data. Data were then codified for anonymity and analyzed. Criteria for inclusion into the analysis involved, i) a minimum of two PrCa biopsies before treatment and ii) detailed reporting of biopsy and clinical results (number of positive cores, % of core involvement, and PSA). Results: A total of 343 AS patient cases were identified in the initial search. Of those 52 cases did not meet inclusion criteria. The baseline GG score distribution in the 291 cases included in the analysis was, GG0: 27 (cases with negative biopsies but high PSA), GG1: 247 and GG2: 17 (patients refusing treatment). A total of 144 cases (49.5%) progressed at re-biopsy. Rates of progression to higher GG category in the three groups were 100%, has 46.5% and 50%, respectively. The average time to progression was 23.3+15.5 months. The rate of progression to treatment after entering AS was 39.17% (114/291). Average time from first biopsy to treatment was (28.4+14.5 months). Amongst those that received treatment the overall rate of progression to high-intermediate or high-risk PrCa, was 29.8%, with 20.8% of cases (30/144) progressing to GG>3 (Gleason Score 7: 4+3 or higher) and 9.0% (13/144) progressing to PSA > 20. Of the treated patients, 70 (61.4%) patients received radiotherapy, 42 (36.8%) combined radiotherapy and androgen deprivation therapy and (31.3%) underwent radical prostatectomy. Conclusions: This retrospective study provides contemporary real-world systematic AS outcomes from a Canadian program with unique features of systematic urological follow up and centralized diagnosis and multi-disciplinary patient assessment. We observe increased rates of disease progression and need for earlier utilization of treatment compared to those reported by other studies. Further analysis examines factors predicting increased risk for disease progression.