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Advances in the selection of patients with prostate cancer for active surveillance

Abstract

Early identification and management of prostate cancer completely changed with the discovery of prostate-specific antigen. However, improved detection has also led to overdiagnosis and consequently overtreatment of patients with low-risk disease. Strategies for the management of patients using active surveillance — the monitoring of clinically insignificant disease until intervention is warranted — were developed in response to this issue. The success of this approach is critically dependent on the accurate selection of patients who are predicted to be at the lowest risk of prostate cancer mortality. The Epstein criteria for clinically insignificant prostate cancer were first published in 1994 and have been repeatedly validated for risk-stratification and selection for active surveillance over the past few decades. Current active surveillance programmes use modified criteria with 30–50% of patients receiving treatment at 10 years. Nonetheless, tools for prostate cancer diagnosis have continued to evolve with improvements in biopsy format and targeting, advances in imaging technologies such as multiparametric MRI, and the identification of serum-, tissue- and urine-based biomarkers. These advances have the potential to further improve the identification of men with low-risk disease who can be appropriately managed using active surveillance.

Key points

  • The current prostate cancer treatment paradigm relies on accurate identification and risk stratification for patients who need immediate intervention versus active surveillance.

  • Epstein criteria for low-risk disease were developed in 1994 and, despite advances in biopsy templates and pathological definitions, the criteria have demonstrated durability over time.

  • Developments in MRI and consequently targeted prostate biopsy have improved cancer detection, especially in anterior tumours. As further research in diagnostic imaging is carried out, this technology may have an increased role in active surveillance protocols.

  • A growing body of research into novel biomarkers in serum, urine and tissue explores new discoveries in cancer genomics to better identify aggressive versus indolent disease.

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Fig. 1: Prostate multiparametric MRI demonstrating how MRI technology and the PI-RADS v2 have improved tumour detection.

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Acknowledgements

The authors thank Yasin Bhanji and Alex J. Solomon for their contribution of MR images for this manuscript. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.3.2020. © National Comprehensive Cancer Network, Inc. 201X. All rights reserved. Accessed January 14th 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

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J.L.L., H.D.P., J.I.E. and A.W.P. researched data for the article, contributed to discussions of its content, wrote the manuscript and participated in review and/or editing of the manuscript before submission. N.M.H. additionally researched data for the article and contributed to discussions of its content.

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Correspondence to James L. Liu.

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Nature Reviews Urology thanks R. Valdagni, A. Finelli and C. Bangma for their contribution to the peer review of this work.

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Box 1 adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.3.2020. © 2020 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data become available. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

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Glossary

PSA

Prostate-specific antigen (PSA) is a glycoprotein enzyme that is prostate specific and one of the first serum tests developed in prostate cancer screening.

PSA density

A calculation of total prostate-specific antigen (PSA) divided by prostate volume. This is helpful in interpreting clinical disease states.

PSA kinetics

The absolute rate of prostate-specific antigen (PSA) change over time. This is helpful in interpreting clinical disease states.

mpMRI fusion-targeted biopsy

A new approach using multi-parametric MRI (mpMRI) technology paired with guided prostate biopsy to provide a more accurate targeting approach.

Total PSA

A blood test that measures the cumulative amount of prostate-specific antigen (PSA) in a patient.

Free PSA

A blood test that measures the amount of PSA that is unbound to blood proteins and could be a helpful predictor in diagnosing prostate cancer.

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Liu, J.L., Patel, H.D., Haney, N.M. et al. Advances in the selection of patients with prostate cancer for active surveillance. Nat Rev Urol 18, 197–208 (2021). https://doi.org/10.1038/s41585-021-00432-w

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