Patients with High-Risk Features on Active Surveillance for Prostate Cancer

With the increasing incidence of prostate cancer worldwide, active surveillance (AS) remains a cornerstone in the management of men with low-risk disease. While the criteria for AS in low-risk prostate cancer are well established, its appropriateness for men with higher-risk features is less clearly defined. This review aims to evaluate the evidence supporting AS in men with a family history of prostate cancer, Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions, and favourable intermediate-risk International Society of Urological Pathology (ISUP) Grade Group (GG) 2 disease. A comprehensive literature review was conducted using PubMed, Embase, and The Cochrane Library. Eligible studies included those assessing outcomes of AS in men with higher-risk features, including family history of prostate or associated malignancies, PI-RADS 4–5 lesions on magnetic resonance imaging (MRI), or favourable-risk ISUP GG2 disease. Studies were excluded if participants had a life expectancy of less than 10 years or had previously received definitive treatment for prostate cancer. Recent evidence suggests that a family history of prostate cancer may confer an increased risk of disease progression on AS; however, current data do not justify exclusion from surveillance on this basis alone. Two single-centre studies demonstrated that men with PI-RADS 5 lesions at AS enrolment exhibited a higher rate of disease upgrading, with 70% progressing to ISUP GG2 and 25–33% to GG3 or higher at confirmatory biopsy. Increasing evidence supports the inclusion of selected men with favourable GG2 disease in AS protocols, provided the absence of high-risk clinical, biochemical, or radiological features. Approximately 50% may require definitive treatment within five years. AS remains a viable management option for appropriately selected men with higher-risk features, accompanied by rigorous monitoring and informed patient counselling. The emerging role of PSMA PET imaging in risk stratification for intermediate-risk disease warrants further investigation through prospective studies.