For patients with low-risk prostate cancer (PCa), active surveillance (AS) is the preferred management strategy across AUA, National Comprehensive Cancer Network, and European Association of Urology guidelines. Given its unanimous support from guidelines statements, AS utilization has been steadily increasing in the US over the last decade, but rates of AS in low-risk PCa patients remain low at only 60% with large variation in AS rates noted on a provider level.¹ This presentation at the AUA2025 Plenary Session focused on high-level evidence available from clinical trials, prospective cohorts, and meta-analyses to provide answers to key clinical questions on AS that can hopefully help its audience increase AS utilization among appropriate patients.

Safety of AS

Initial randomized clinical trials supporting the safety of AS (Scandinavian Prostate Cancer Group Study Number 4 in Scandinavia and Prostate Intervention Versus Observation Trial in the United States) randomized patients to radical prostatectomy (RP) vs watchful waiting (WW) and showed no difference in prostate cancer–specific mortality (PCSM) between the 2 groups.^2,3 More recently, the Prostate Testing for Cancer and Treatment (ProtecT) trial in the United Kingdom randomized 1643 patients to RP, radiation therapy, and active monitoring.⁴ While there was a slightly higher rate of metastatic disease in the active monitoring arm, there was again no difference in PCSM between active monitoring and the definitive treatment groups. Notably, the active monitoring arm in ProtecT was more similar to many current AS protocols than WW, as PSA increases triggered biopsies, and approximately 50% of patients underwent definitive treatment at 8 years of follow-up. Given that contemporary AS protocols are more intensive than WW in the active monitoring arm of ProtecT, these trials support the safety of AS in low-risk patients.

Contemporary AS protocols are more rigorous, as they incorporate protocol-directed biopsies at regular intervals regardless of PSA kinetics. Prospective, multi-institutional contemporary AS cohorts (Canary PASS [Prostate Active Surveillance Study], PRIAS [Prostate Cancer Research International Active Surveillance Study], and Movember GAP3 [Global Action Plan Prostate Cancer Active Surveillance]) have all demonstrated that inclusion of protocol-directed biopsies results in exceedingly low rates of metastasis (~1% at 10 years) and PCSM (<0.5% at 10 years), with approximately 50% of patients undergoing definitive treatment at ~10 years of follow-up.^5-7

While these studies highlight the safety of AS, there are still patients with low-risk PCa who may not be ideal candidates for AS. A recent meta-analysis of AS cohorts showed that high PSA density and high tumor volume were associated with an increased risk of reclassification on AS.⁸ If these adverse clinical factors are present in patients considering AS, they should be acknowledged during shared decision-making.

Deintensification of AS

Given its high safety in low-risk PCa, patients often remain on AS for many years. During that time there is likely a role for deintensification of AS in select patients. Deintensification involves increasing the time between periodic surveillance biopsies while on AS. Patients with prior negative surveillance biopsy, especially multiple negative biopsies, represent ideal candidates for deintensification as both prospective cohort studies and a meta-analysis have shown this is strongly protective against experiencing reclassification while on AS.^9,10

Can MRI Replace Surveillance Biopsies?

A central point to this clinical question is that MRI performance appears to differ in the initial diagnostic setting compared to its performance in AS cohorts. Large institutional studies at high-volume MRI centers have shown that the negative predictive value of MRI in AS cohorts is modest, ranging from 70% to 80%, with 31% to 36% of reclassifications identified outside MRI lesions on systematic biopsies.^11,12 This suggests MRI cannot replace periodic surveillance biopsies.

ASIST (Active Surveillance Magnetic Resonance Imaging Study) was a randomized clinical trial of 273 patients who were randomized at confirmatory biopsy to either 12-core systematic biopsy or MRI with targeted and systematic biopsies.¹³ This trial showed no difference in upgrading rates at confirmatory biopsy between the 2 arms, suggesting minimal added benefit of MRI. However, the 2-year follow-up study of the ASIST trial showed fewer AS failures and fewer reclassifications in the MRI group, suggesting that MRI may be beneficial yet still cannot replace periodic biopsies while on AS.

There have been significant efforts focused on whether changes in serial MRIs over time may provide additional information that could allow surveillance biopsies to be safely avoided. To standardize reporting changes in patients with serial MRIs, the PRECISE (Prostate Cancer Radiological Estimation of Change in Sequential Evaluation) scoring system was developed in 2016. A meta-analysis of serial MRIs in AS cohorts showed that the negative predictive value was still only 81% to 87%, and this was similar in the subset of studies using PRECISE scores.¹⁴ Furthermore, changes in serial MRI could not accurately predict disease progression. These studies highlight that while helpful, MRI alone cannot replace periodic surveillance biopsies for patients on AS, which is concordant with current AUA and European Association of Urology guidelines.

Inclusion of Intermediate-Risk Patients

Another major timely topic is the safety of intermediate-risk patients for AS. Prospective institutional cohorts and meta-analyses have shown that intermediate-risk PCa is associated with higher rates of definitive treatment, adverse pathology at RP, recurrence after RP, metastases, and PCSM compared to low-risk disease.^4,15,16 However, there are select patients with intermediate-risk disease who remain good candidates for AS. Based on prior studies, these patients are those with favorable intermediate-risk disease with low PSA density, low tumor volume, and low percentage pattern 4 disease without cribriform or intraductal histology. Even with a favorable risk profile, all patients with intermediate-risk disease pursuing AS should be appropriately counseled regarding their risk of adverse outcomes being higher than in patients with low-risk disease.

These sources of high-level evidence address practical clinical questions related to AS, facilitate increased AS utilization, support identification of appropriate candidates for AS, establish the limitations of MRI during AS, and provide pragmatic information that will help in patient-provider shared decision-making for lower-risk prostate cancer.

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