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Neoadjuvant radiotherapy for locally advanced and high-risk prostate cancer

Nature Reviews Clinical Oncology volume 8, pages 107–113 (2011)Cite this article

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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

  • 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

  • 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

  • Preoperative or intraoperative radiotherapy followed by surgery is a potentially effective therapy, having both advantages and disadvantages when compared with postoperative radiotherapy

  • 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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Figure 1: Biomarkers of prostate cancer response following radiotherapy.

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References

  1. NCI. Prostate Cancer Treatment: Stage III prostate cancer [online],

  2. Johansson, J. E., Holmberg, L., Johansson, S., Bergström, R. & Adami, H. O. Fifteen-year survival in prostate cancer. A prospective, population-based study in Sweden. JAMA 277, 467–471 (1997).

    Article  CAS  Google Scholar 

  3. Heidenreich, A. et al. EAU guidelines on prostate cancer. Eur. Urol. 53, 68–80 (2008).

    Article  Google Scholar 

  4. National Comprehensive Cancer Network. Clinical Practice Guidelines [online],

  5. Bolla, M. et al. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet 366, 572–578 (2005).

    Article  Google Scholar 

  6. Thompson, I. M. Jr et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA 296, 2329–2335 (2006).

    Article  CAS  Google Scholar 

  7. Thompson, I. M. et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term follow up of a randomized clinical trial. J. Urol. 181, 956–962 (2009).

    Article  Google Scholar 

  8. Wiegel, T. et al. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate specific antigen: (ARO 96–02/AUO AP 09/95). J. Clin. Oncol. 27, 2924–2930 (2009).

    Article  Google Scholar 

  9. Bolla, M. et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 360, 103–106 (2002).

    Article  CAS  Google Scholar 

  10. Bolla, M. et al. Ten-year results of long term adjuvant androgen deprivation with goserelin in patients with locally advanced prostate cancer treated with radiotherapy: a phase III EORTC study. Int. J. Radiat. Oncol. Biol. Phys. 72, S30–S31 (2008).

    Article  Google Scholar 

  11. Carver, B. S., Bianco, F. J. Jr, Scardino, P. T. & Eastham, J. A. Long-term outcome following radical prostatectomy in men with clinical stage T3 prostate cancer. J. Urol. 176, 564–568 (2006).

    Article  Google Scholar 

  12. Gerber, G. S. et al. Results of radical prostatectomy in men with locally advanced prostate cancer: multi-institutional pooled analysis. Eur. Urol. 32, 385–390 (1997).

    CAS  PubMed  Google Scholar 

  13. Hanks, G. E. et al. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92–02. J. Clin. Oncol. 21, 3972–3978 (2003).

    Article  CAS  Google Scholar 

  14. Hsu, C. Y., Joniau, S., Oyen, R., Roskams, T. & Van Poppel, H. Outcome of surgery for clinical unilateral T3a prostate cancer: a single-institution experience. Eur. Urol. 51, 121–128 (2007).

    Article  Google Scholar 

  15. Lawton, C. A. et al. Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85-31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate. Int. J. Radiat. Oncol. Biol. Phys. 49, 937–946 (2001).

    Article  CAS  Google Scholar 

  16. Lerner, S. E., Blute, M. L. & Zincke, H. Extended experience with radical prostatectomy for clinical stage T3 prostate cancer: outcome and contemporary morbidity. J. Urol. 154, 1447–1452 (1995).

    Article  CAS  Google Scholar 

  17. Pilepich, M. V. et al. Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Int. J. Radiat. Oncol. Biol. Phys. 50, 1243–1252 (2001).

    Article  CAS  Google Scholar 

  18. Roach, M. 3rd et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J. Clin. Oncol. 26, 585–591 (2008).

    Article  Google Scholar 

  19. Ward, J. F., Slezak, J. M., Blute, M. L., Bergstralh, E. J. & Zincke, H. Radical prostatectomy for clinically advanced (cT3) prostate cancer since the advent of prostate-specific antigen testing: 15-year outcome. BJU Int. 95, 751–756 (2005).

    Article  Google Scholar 

  20. Bayley, A. et al. Clinical application of high-dose, image-guided intensity-modulated radiotherapy in high-risk prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 77, 477–483 (2009).

    Article  Google Scholar 

  21. Heidenreich, A. & Ohlmann, C. H. The role of pelvic lymphadenectomy in the therapy of prostate and bladder cancer [German]. Aktuelle Urol. 36, 219–229 (2005).

    Article  CAS  Google Scholar 

  22. Swanson, G. P. et al. Predominant treatment failure in postprostatectomy patients is local: analysis of patterns of treatment failure in SWOG 8794. J. Clin. Oncol. 25, 2225–2229 (2007).

    Article  Google Scholar 

  23. van der Kwast, T. H. et al. Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911. J. Clin. Oncol. 25, 4178–4186 (2007).

    Article  Google Scholar 

  24. van der Kwast, T. H., Collette, L. & Bolla, M. Adjuvant radiotherapy after surgery for pathologically advanced prostate cancer. J. Clin. Oncol. 25, 5671–5672 (2007).

    Article  Google Scholar 

  25. Klotz, L. H. et al. Long-term follow up of a randomized trial of 0 versus 3 months of neoadjuvant androgen ablation before radical prostatectomy. J. Urol. 170, 791–794 (2003).

    Article  CAS  Google Scholar 

  26. Yee, D. S. et al. Long-term follow-up of 3-month neoadjuvant hormone therapy before radical prostatectomy in a randomized trial. BJU Int. 105, 185–190 (2010).

    Article  CAS  Google Scholar 

  27. Carson, C. C. 3rd, Zincke, H., Utz, D. C., Cupps, R. E. & Farrow, G. M. Radical prostatectomy after radiotherapy for prostatic cancer. J. Urol. 124, 237–239 (1980).

    Article  Google Scholar 

  28. Garzotto, M., Hung., A., Beer, T. F. & Farris, P. Phase I study of preoperative radiation and docetaxel for high-risk prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 75 (Suppl. 3), S13 (2009).

    Article  Google Scholar 

  29. Koontz, B. F. et al. Preliminary results of a phase I trial of preoperative radiotherapy for high-risk localized prostate cancer [abstract 78]. ASCO Genitourinary Cancers Symposium (2009).

    Google Scholar 

  30. Krengli, M. A. et al. Intraoperative radiotherapy during radical prostatectomy for locally advanced prostate cancer: technical and dosimetric aspects. Int. J. Radiat. Oncol. Biol. Phys. 76, 1073–1077 (2010).

    Article  Google Scholar 

  31. Rocco, B. et al. Intraoperative radiotherapy during radical prostatectomy for intermediate-risk to locally advanced prostate cancer: treatment technique and evaluation of perioperative and functional outcome vs standard radical prostatectomy, in a matched-pair analysis. BJU Int. 104, 1624–1630 (2009).

    Article  Google Scholar 

  32. Supiot, S. et al. A phase I trial of pre-operative radiotherapy for prostate cancer: clinical and translational studies. Radiother. Oncol. 88, 53–60 (2008).

    Article  Google Scholar 

  33. Fowler, J. F. The radiobiology of prostate cancer including new aspects of fractionated radiotherapy. Acta Oncol. 44, 265–276 (2005).

    Article  Google Scholar 

  34. [No authors listed] Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N. Engl. J. Med. 336, 980–987 (1997).

  35. Birgisson, H., Pahlman, L., Gunnarsson, U., Glimelius, B. & Swedish Rectal Cancer Trial Group. Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial. J. Clin. Oncol. 23, 8697–8705 (2005).

    Article  Google Scholar 

  36. Folkesson, J. et al. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J. Clin. Oncol. 23, 5644–5650 (2005).

    Article  Google Scholar 

  37. Kapiteijn, E. et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N. Engl. J. Med. 345, 638–646 (2001).

    Article  CAS  Google Scholar 

  38. Peeters, K. C. et al. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann. Surg. 246, 693–701 (2007).

    Article  Google Scholar 

  39. Sauer, R. et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N. Engl. J. Med. 351, 1731–1740 (2004).

    Article  CAS  Google Scholar 

  40. Sebag-Montefiore, D. et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet 373, 811–820 (2009).

    Article  Google Scholar 

  41. O'Sullivan, B. et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet 359, 2235–2241 (2002).

    Article  Google Scholar 

  42. Zelefsky, M. J. et al. Long-term results of conformal radiotherapy for prostate cancer: impact of dose escalation on biochemical tumor control and distant metastases-free survival outcomes. Int. J. Radiat. Oncol. Biol. Phys. 71, 1028–1033 (2008).

    Article  Google Scholar 

  43. Thoms, J., Bristow, R., Warde, P. & Supiot, S. Response to “Intraoperative radiotherapy during radical prostatectomy for locally advanced prostate cancer: technical and dosimetric aspects” (Int J Radiat Oncol Biol Phys 2009; in press). Int. J. Radiat. Oncol. Biol. Phys. 76, 1277 (2009).

    Article  Google Scholar 

  44. Hotte, S. J., Winquist, E. W., Stitt, L. & Chambers, A. F. Plasma osteopontin: associations with survival and metastasis to bone in men with hormone-refractory prostate carcinoma. Cancer 95, 506–512 (2002).

    Article  CAS  Google Scholar 

  45. Russo, A. L. et al. Urine analysis and protein networking identify met as a marker of metastatic prostate cancer. Clin. Cancer Res. 15, 4292–4298 (2009).

    Article  CAS  Google Scholar 

  46. Lapointe, J. et al. Genomic profiling reveals alternative genetic pathways of prostate tumorigenesis. Cancer Res. 67, 8504–8510 (2007).

    Article  CAS  Google Scholar 

  47. Reid, A. H. et al. Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer. Br. J. Cancer 102, 678–684 (2010).

    Article  CAS  Google Scholar 

  48. Vickers, A. J. et al. Effects of pathologic stage on the learning curve for radical prostatectomy: evidence that recurrence in organ-confined cancer is largely related to inadequate surgical technique. Eur. Urol. 53, 960–966 (2008).

    Article  Google Scholar 

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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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Authors and Affiliations

  1. Radiation Medicine Program, Princess Margaret Hospital, University Health Network, 5th Floor, Room 5-808, 610 University Avenue, Toronto, M5G 2M9, ON, Canada

    John Thoms, Padraig Warde & Robert G. Bristow

  2. Division of Urology, Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, 5th Floor, Room 5-808, 610 University Avenue, Toronto, M5G 2M9, ON, Canada

    Alexender R. Zlotta & Neil E. Fleshner

  3. Department of Pathology, Princess Margaret Hospital, University Health Network, 5th Floor, Room 5-808, 610 University Avenue, Toronto, M5G 2M9, ON, Canada

    Theodorus H. van der Kwast

  4. Department of Radiation Oncology, Tata Memorial Center, 400 021, Mumbai, India

    Jayant S. Goda

  5. Department of Radiation Oncology, Center René Gauducheau, 44800, Nantes St Herblain, France

    Stéphane Supiot

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Contributions

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.

Corresponding author

Correspondence to Robert G. Bristow.

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The authors declare no competing financial interests.

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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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