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  • Review Article
  • Published:

High-risk prostate cancer—classification and therapy

Key Points

  • Patients with high-risk prostate cancer have a significant chance of developing systemic or local recurrence, and are at higher risk for symptoms and/or death from the disease

  • Definitions vary for what constitutes high-risk disease in localized prostate cancer, but are historically based on clinicopathological findings including clinical stage, Gleason score, and PSA

  • The literature is limited as a consequence of variations in definition, lack of prospective randomized trials, limitations in statistical plan (underpowered studies), the need for long-term follow-up, and suboptimal end points

  • Several key principles for radiotherapy have been established, including the importance of dose, and the addition of androgen-deprivation therapy

  • Optimal surgical management requires completely removing the gland itself, confirming negative margins intraoperatively, and discussing the potential need for post-operative radiotherapy

  • Treatment of potential lymph-node involvement, either surgically or with extended pelvic radiation, is favoured in high-risk disease, but lacks level I evidence

Abstract

Approximately 15% of patients with prostate cancer are diagnosed with high-risk disease. However, the current definitions of high-risk prostate cancer include a heterogeneous group of patients with a range of prognoses. Some have the potential to progress to a lethal phenotype that can be fatal, while others can be cured with treatment of the primary tumour alone. The optimal management of this patient subgroup is evolving. A refined classification scheme is needed to enable the early and accurate identification of high-risk disease so that more-effective treatment paradigms can be developed. We discuss several principles established from clinical trials, and highlight other questions that remain unanswered. This Review critically evaluates the existing literature focused on defining the high-risk population, the management of patients with high-risk prostate cancer, and future directions to optimize care.

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Figure 1: Clinical states of prostate cancer.

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Acknowledgements

The authors thank Amy Plofker, MSKCC editor, for her superb editorial assistance. This work was supported at Memorial Sloan–Kettering Cancer Center by The Sidney Kimmel Center for Prostate and Urologic Cancers, the MSKCC SPORE in Prostate Cancer (P50 CA92629) (H.I.S.), the Department of Defense Prostate Cancer Research Program (PC051382, PC121111) (H.I.S.), and The Prostate Cancer Foundation (H.I.S.). This work was supported at the University of California, San Francisco by the Helen Diller Family Cancer Center (M.R.), NRG Oncology (M.R.), University of California San Francisco Resource Allocation Program (A.J.C.), and General Electric ISR (A.J.C.).

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All authors researched the data for the article, contributed substantially to discussion of content, wrote and reviewed and edited the manuscript before submission.

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Correspondence to Mack Roach III or Howard I. Scher.

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M.R. declares associations with Astellas, Bayer and Varian. H.I.S. declares associations with Astellas, Bristol-Myers Squibb, Janssen, Medivation, Millennium, and Sanofi. The other authors declare no competing interests.

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Chang, A., Autio, K., Roach, M. et al. High-risk prostate cancer—classification and therapy. Nat Rev Clin Oncol 11, 308–323 (2014). https://doi.org/10.1038/nrclinonc.2014.68

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