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Resolving the Optimal Timing of Radiotherapy After Radical Prostatectomy: The Need for Further Research

Academic Urology Unit, Royal Marsden Hospital; Institute of Cancer Research, Sutton, United Kingdom

Matthew R. Sydes

Clinical Trials Unit, Medical Research Council, London, United Kingdom

To the Editor:

Van der Kwast and colleagues¹ recently provided an excellent summary of the published randomized controlled trials of postoperative radiotherapy after radical prostatectomy. They highlight remaining areas of uncertainty and, in particular, the ongoing doubt concerning the optimum timing of postoperative treatment.

The possibility of a second wave of metastases arising from residual local disease, before elevation of serum prostate-specific antigen (PSA) levels is detected, is a strong argument for immediate (adjuvant) radiotherapy. In contrast, the financial cost and the morbidity of radiotherapy, together with the pattern of failure analysis of the Southwest Oncology Group 8794 trial,² argue for a policy of deferred (salvage) radiotherapy at the time of PSA failure.

Given the large number of men treated with radical prostatectomy and the trend towards surgical treatment of men with high-risk and locally advanced disease, the optimum timing of postoperative radiotherapy is an important and unresolved issue. The completed randomized trials^3-5 described by Van der Kwast et al,¹ although valuable, do little to resolve this issue because they compared immediate radiotherapy with a policy of deferring radiotherapy until clinical (and not biochemical) progression.

A large-scale randomized controlled trial is required to study the timing of postoperative radiotherapy with respect to long-term clinical outcomes. The recently opened Radiotherapy and Androgen Deprivation in Combination After Local Surgery (RADICALS) trial⁶ is an Intergroup phase III trial, run by the Medical Research Council Clinical Trials Unit in the United Kingdom, and by the National Cancer Institute Clinical Trials Group in Canada, that aims to recruit over 4,000 patients (ISRCTN40814031 [controlled-trials.com] ). The trial has a pragmatic design: men who have had a radical prostatectomy, and for whom there is uncertainty regarding the optimum timing of postoperative radiotherapy, may be randomly assigned to either adjuvant radiotherapy or early salvage radiotherapy at PSA failure. This is the Radiotherapy Timing Randomisation and will recruit around 2,700 patients. In addition, all men receiving postoperative radiotherapy, whether in the adjuvant or salvage setting, may also be randomized between radiotherapy alone, radiotherapy plus 6 months of hormone therapy, or radiotherapy plus 24 months of hormone therapy (Hormone Duration Randomisation). The RADICALS recruitment target is ambitious but achievable.

We are grateful to Van der Kwast and his colleagues for highlighting the uncertainty regarding the optimum timing of postoperative radiotherapy following radical prostatectomy. This uncertainty can only be resolved by appropriately designed phase III trials. Centers or trial groups that would be interested in taking part in the RADICALS trial are invited to contact the Medical Research Council's Clinical Trials Unit by visiting their Web site.⁷

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: Matthew R. Sydes, Medical Research Council Trials Unit) (C) Consultant or Advisory Role: None Stock Ownership: None Honoraria: None Research Funding: Christopher Parker, Cancer Research UK; Matthew R. Sydes, Cancer Research UK, Medical Research Council, UK Expert Testimony: None Other Remuneration: None

REFERENCES

1. Van der Kwast TH, Collette L, Bolla M: Adjuvant Radiotherapy After Surgery for Pathologically Advanced Prostate Cancer. J Clin Oncol 25:5671-5672, 2007[Free Full Text]

2. Swanson GP, Hussey MA, Tangen CM, 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[Abstract/Free Full Text]

3. Bolla M, Van Poppel H, Collette L, et al: Postoperative radiotherapy after radical prostatectomy: A randomised controlled trial (EORTC trial 22911). Lancet 366:572-578, 2005[CrossRef][Medline]

4. Wiegel T, Bottke D, Willich N, et al: Phase III results of adjuvant radiotherapy (RT) versus "wait and see" (WS) in patients with pT3 prostate cancer following radical prostatectomy (RP) (ARO 96-02/AUO AP 09/95). J Clin Oncol 23:16s, 2005 (suppl; abstr 4573)

5. Thompson IM Jr, Tangen CM, Paradelo J, et al: Adjuvant radiotherapy for pathologically advanced prostate cancer: A randomized clinical trial. JAMA 296(19):2329-2335, 2006[Abstract/Free Full Text]

6. RADICALS: MRC PR10, NCIC PR13, ISRCTN40814031. http://www.controlled-trials.com/cctspringview2/mrct/showTrial.html?mrid=240531&srch=. 2008

7. MRC PR10: RADICALS study. http://www.ctu.mrc.ac.uk/studies/PR10.asp

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Parker, C. Articles by Sydes, M. R. Search for Related Content PubMed PubMed Citation Articles by Parker, C. Articles by Sydes, M. R. Social Bookmarking                            What's this?