Active Surveillance in Intermediate-Risk Prostate Cancer: A Contemporary Synthesis of Evidence

Active surveillance (AS) is a widely accepted strategy for low-risk prostate cancer, but its application to intermediate-risk disease remains controversial. Given the potential to reduce overtreatment without compromising survival, this review evaluates the safety and clinical outcomes of AS in intermediate-risk prostate cancer (IR-PCa), with a focus on favorable intermediate-risk (FIR) subsets. The objective is to synthesize current evidence on AS utilization, selection criteria, oncologic outcomes, and predictors of disease progression.We conducted a narrative review of 85 studies published between 2009 and 2025 identified through PubMed, Embase, and Web of Science. Search terms included “AS,” “intermediate-risk prostate cancer,” “Gleason 3 + 4,” and “watchful waiting.” Eligible studies included prospective and retrospective cohorts, registry-based analyses, and comparative observational studies evaluating AS in IR-PCa. Data were extracted regarding inclusion criteria, follow-up protocols, progression rates, survival outcomes, and use of imaging and genomic tools for risk stratification. AS is increasingly used in FIR patients with low-volume Gleason 3 + 4 disease, low PSA density, and favorable imaging/genomic profiles. In these patients, 5-10 year metastasis-free survival exceeds 95%. However, AS in unfavorable IR disease is associated with higher risks of disease progression and prostate cancer–specific mortality. Limitations include heterogeneity in AS protocols, lack of randomized trials, and variable definitions of FIR. AS is a viable option for well-selected FIR-PCa patients. Incorporating PSA density, mpMRI, and genomic testing enhances risk stratification. Clinical guidelines should support tailored AS approaches with standardized follow-up and timely intervention triggers.