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.