Abstract
Men presenting with high-risk or locally advanced prostate cancer may benefit from a combination of radiotherapy and surgery to maximize local control. Adjuvant radiotherapy following surgery has improved biochemical progression-free survival, metastasis-free survival, lengthened the time to hormone therapy use and improved overall survival in three randomized-phase III trials. One surprising result of the Southwest Oncology Group (SWOG) 8794 trial and the European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial is that treatment failure was mainly a result of lack of local control. This finding has led to a new appreciation of local control as a determinant of survival and the role for combined modality approaches within a multidisciplinary team in the treatment of high-risk and locally advanced prostate cancer. One emerging novel approach is the use of preoperative or intraoperative radiotherapy in addition to best surgical and systemic treatments. Preliminary results from clinical trials indicate low rates of intraoperative toxic effects, an advantage of short treatment times and smaller image-guided radiotherapy treatment volumes when compared with postoperative radiotherapy. Potential disadvantages include over-treatment of patients and lack of data on long-term toxic effects. We present the published treatment approaches and rational for preoperative and intraoperative radiotherapy and compare these methods to the utility of postoperative radiotherapy.
Key Points
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Men with locally advanced or high-risk prostate cancer are at a high risk of local recurrence; these men may benefit from combined modality strategies to maximize local control
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Randomized clinical trials of adjuvant postoperative radiotherapy support an improvement in local control and perhaps survival in patients with locally advanced or high-risk prostate cancer
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Preoperative or intraoperative radiotherapy followed by surgery is a potentially effective therapy, having both advantages and disadvantages when compared with postoperative radiotherapy
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Clinical trials are required to define the factors that will best select patients for preoperative or intraoperative radiotherapy compared with postoperative radiotherapy
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Acknowledgements
This work is funded by a Terry Fox Foundation Program Grant (15004), a CCSRI Operating Grant (17154) a Canadian Foundation for Innovation grant to the STTARR Innovation Facility and a grant from Prostate Cancer Canada. This work was funded in part by the Radiation Medicine Program, Princess Margaret Hospital and National Cancer Institute of Canada. The authors would like to thank John Tsihlias, Laurence Klotz, Cynthia Menard, Charles Catton and Michael Milosevic for helpful comments and discussions. C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.
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J. Thoms and R. G. Bristow contributed equally to the discussion of content for the article, researched data to include in the manuscript, reviewed and edited the manuscript before submission, and revised the manuscript in response to the peer-reviewers' comments. J. S. Goda researched data and contributed to the writing of the article. A. R. Zlotta, N. E. Fleshner, T. H. van der Kwast, S. Supiot and P. Warde each provided a substantial contribution to the discussion of content and to reviewing, editing and revising the manuscript.
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Thoms, J., Goda, J., Zlotta, A. et al. Neoadjuvant radiotherapy for locally advanced and high-risk prostate cancer. Nat Rev Clin Oncol 8, 107–113 (2011). https://doi.org/10.1038/nrclinonc.2010.207
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DOI: https://doi.org/10.1038/nrclinonc.2010.207
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