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Surgical management of high-risk, localized prostate cancer


High-risk prostate cancer is a heterogeneous disease that lacks clear consensus on its ideal management. Historically, non-surgical treatment was the preferred strategy, and several studies demonstrated improved survival among men with high-risk disease managed with the combination of radiotherapy and androgen deprivation therapy (ADT) compared with ADT alone. However, practice trends in the past 10–15 years have shown increased use of radical prostatectomy with pelvic lymph node dissection for primary management of high-risk, localized disease. Radical prostatectomy, as a primary monotherapy, offers the potential benefits of avoiding ADT, reducing rates of symptomatic local recurrence, enabling full pathological tumour staging and potentially reducing late adverse effects such as secondary malignancy compared with radiation therapy. Retrospective studies have reported wide variability in short-term (pathological) and long-term (oncological) outcomes of radical prostatectomy. Surgical monotherapy continues to be appropriate for selected patients, whereas in others the best treatment strategy probably involves a multimodal approach. Appropriate risk stratification utilizing clinical, pathological and potentially also genomic risk data is imperative in the initial management of men with prostate cancer. However, data from ongoing and planned prospective trials are needed to identify the optimal management strategy for men with high-risk, localized prostate cancer.

Key points

  • High-risk prostate cancer is a heterogeneous disease that varies in its clinical aggressiveness and associated oncological outcomes.

  • Effective staging of high-risk prostate cancer is limited by the poor diagnostic performance of conventional imaging; however, novel imaging modalities are being developed.

  • Level I data on the role of radical prostatectomy in the management of high-risk, localized prostate cancer are currently scarce.

  • Clinical, pathological and genomic markers of tumour responsiveness to hormonal therapy, resistance to radiation and risk of metastatic progression will also improve the stratification of patients with high-risk prostate cancer.

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Fig. 1: Definitions of high-risk prostate cancer.
Fig. 2: Pelvic lymph node dissection templates used in the treatment of prostate cancer.
Fig. 3: Considerations in the treatment of newly diagnosed, high-risk prostate cancer.


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Y.A.N., L.J.W., J.J.T., D.S., A.E.R., E.A.K. and B.F.C. 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. D.G. additionally researched data for the article and contributed to discussions of its content.

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Correspondence to Yaw A. Nyame.

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B.F.C. declares that he is a consultant and adviser for Blue Earth Diagnostics and Janssen and has received research funding from Janssen. The other authors declare no competing interests.

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Nature Reviews Urology thanks Q.-D. Trinh, N. Mottet, J. Stranne and F. Hamdy for their contribution to the peer review of this work.

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Wilkins, L.J., Tosoian, J.J., Sundi, D. et al. Surgical management of high-risk, localized prostate cancer. Nat Rev Urol 17, 679–690 (2020).

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