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  • Review Article
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The status of surgery in the management of high-risk prostate cancer

Key Points

  • Depending on the classification system used, 3–35% of patients with newly diagnosed prostate cancer have high-risk disease; outcomes are heterogeneous among this group and prognoses are not always poor

  • Without clear evidence of superiority, radiation therapy combined with androgen-deprivation therapy (ADT) has become the standard-of-care treatment for patients with high-risk disease; however, increasingly patients are initially treated surgically

  • Surgery for high-risk disease, as part of multimodal therapy, has comparable efficacy to radiotherapy with ADT; therefore, primary surgery, with or without adjuvant radiotherapy, is a viable treatment option

  • Surgery enables accurate histopathological assessment, local disease control and potentially reduces the risk of metastasis; concomitant extended lymphadenectomy might improve survival and identify patients in whom immediate ADT is indicated

  • Downstaging and downgrading of tumours in a substantial proportion of patients suggest that they would have been overtreated if radiotherapy and ADT were used

  • A multimodal approach to therapy including surgery, radiotherapy, and neoadjuvant and/or adjuvant ADT should be offered to men with high-risk prostate cancer, but the optimal protocols remain to be determined

Abstract

Although the optimal treatment for patients with high-risk prostate cancer remains unclear, combined radiotherapy and androgen-deprivation therapy (ADT) has become the standard of care; however, more recently, this paradigm has been challenged. In contemporary surgical series, using a multimodal approach with primary radical prostatectomy and adjuvant radiotherapy, when appropriate, had comparable efficacy in patients with high-risk disease to radiotherapy in combination with ADT. Furthermore, perioperative and postoperative morbidity associated with radical prostatectomy seem to be similar in patients with low-risk, intermediate-risk, or high-risk prostate cancer. Importantly, downstaging and downgrading of a substantial proportion of tumours after surgery suggests that many patients might be overtreated using radiotherapy and ADT. Indeed, the potential benefits of surgery include the ability to obtain tissues that can provide accurate histopathological information and, therefore, guide further disease management, in addition to local control of disease, a potentially reduced risk of developing metastases, and avoidance of long-term ADT. Thus, patients with high-risk disease should be offered a choice of first-line treatments, including surgery. However, effective management of high-risk prostate cancer is likely to require a multimodal approach, including surgery, radiotherapy, and neoadjuvant and adjuvant ADT, although the optimal protocols remain to be determined.

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C.B. researched the data for the article. C.B., M.W., E.R., D.G., R.P. and A.K. made substantial contributions to discussion of content, and C.B., S.P., D.D. and A.K. contributed to writing the article. In addition, C.B. and A.K. reviewed/edited the manuscript before submission.

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Correspondence to Anthony Koupparis.

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Bach, C., Pisipati, S., Daneshwar, D. et al. The status of surgery in the management of high-risk prostate cancer. Nat Rev Urol 11, 342–351 (2014). https://doi.org/10.1038/nrurol.2014.100

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