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In Reply

Department of Radiation Oncology, Léon Bérard Center, Lyon France

Sylvie Chabaud

Department of Biostatistics, Léon Bérard Center, Lyon, France

We would like first to thank Drs Nguyen and D'Amico for their important comments and conclusions. The results of the Groupe d'Etude des Tumeurs Uro-Génitales (GETUG)–01 and the Radiation Therapy Oncology Group (RTOG) 94-13 trials are indeed important landmarks that should directly impact radiation oncologists' practice in prostate cancer radiotherapy.^1-3

In daily practice, the decision to irradiate pelvic nodes was based on the probability of pelvic nodes involvement assessed by predictive models (mainly the Partin tables and the Roach formula) and on the belief that radiotherapy would permit regional control of the disease that would lead to a significant clinical benefit in terms of cancer cure, without impairing the patient's quality of life.

One important contribution of the GETUG-01 was to show that pelvic irradiation with the modalities described in that protocol did not significantly impair patients' quality of life in the long-term. Moreover, in that situation, the diffusion of the use of intensity-modulated radiation therapy will certainly reduce the risk of acute and late toxicities.⁴

However, three prospective randomized studies failed to prove any clinical benefit of pelvic radiotherapy in prostate cancer; moreover, these studies also failed to identify any subgroups that might beneficiate from pelvic radiotherapy ^1-3,5,6. Indeed, the most important conclusion from the updated results of the RTOG 94-13 is that there may be an interaction between timing of hormonal therapy and radiotherapy resulting in an apparent negative interaction between whole pelvic radiotherapy and adjuvant hormonal therapy, at least for the overall survival probability. Therefore, the differences observed between whole pelvic irradiation and prostate-only irradiation in the subgroup of patients treated with neoadjuvant and concomitant androgen suppression cannot be clearly attributed to pelvic node irradiation.

We agree with Drs Nguyen and D'Amico that there is still no demonstration of the clinical advantage of pelvic radiotherapy, and that this irradiation should not be considered as a standard of care in routine practice for N0,pNx, M0 prostate cancer patients.

However, as was emphasized in the GETUG-01 discussion section and in the comments from Drs Nguyen and D'Amico, there are several limitations that may have contributed to the negative conclusion of this study: population selection with many patients unlikely to have nodes involvement, radiotherapy modalities (volume and dose), and heterogeneity in hormonal therapy.

We are interested in the proposal of another randomized study to assess the role of pelvic radiotherapy in prostate cancer. The patient selection criteria should, as proposed, include high-risk patients for nodal involvement, but also must take into account the competitive risk of distant metastases. This could lead to stricter patient selection (ie, excluding patients with Gleason score 8 and/or seminal vesicle involvement), and use and assessment of new techniques such as magnetic resonance imaging, ¹⁸F-choline, positron emission tomography, and sentinel nodes for the work-up. This additional study should also benefit from modern intensity-modulated radiation therapy (and image-guided radiation therapy) techniques associated with an important and challenging quality assurance program to define and have an agreement on radiotherapy modalities (eg, clinical target volumes, dose).^7,8

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

ACKNOWLEDGMENTS

The GETUG-01 study was promoted and financed by the "Groupe d'Etude des Tumeurs Uro-Genitales" (French Genito-Urinary Group) of the Fédération Nationale des Centres de Lutte Contre le Cancer, with a grant from the Ligue Nationale Contre le Cancer.

REFERENCES

1. Pommier P, Chabaud S, Lagrange JL, et al: Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Preliminary results of GETUG-01. J Clin Oncol 25:5366-5373, 2007[Abstract/Free Full Text]

2. Lawton CA, DeSilvio M, Roach M III, et al: An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: Updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys 69:646-655, 2007[Medline]

3. Roach M III, DeSilvio M, Lawton C, et al: Phase III trial comparing whole-pelvic prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol 21:1904-1911, 2003[Abstract/Free Full Text]

4. Wang-Chesebro A, Xia P, Coleman J, et al: Intensity-modulated radiotherapy improves lymph node coverage and dose to critical structures compared with three-dimensional conformal radiation therapy in clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 66:654-662, 2006[Medline]

5. Asbell SO, Krall JM, Pilepich MV, et al: Elective pelvic irradiation in stage A2, B carcinoma of the prostate: Analysis of RTOG 77-06. Int J Radiat Oncol Biol Phys 15:1307-1316, 1988[Medline]

6. Asbell SO, Martz KL, Shin KH, et al: Impact of surgical staging in evaluating the radiotherapeutic outcome in RTOG #77-06, a phase III study for T1BN0M0 (A2) and T2N0M0 (B) prostate carcinoma. Int J Radiat Oncol Biol Phys 40:769-782, 1998[CrossRef][Medline]

7. Ganswindt U, Paulsen F, Corvin S, et al: Optimized coverage of high- risk adjuvant lymph node areas in prostate cancer using a sentinel node–based, intensity-modulated radiation therapy technique. Int J Radiat Oncol Biol Phys 67:347-355, 2007[Medline]

8. Lawton CA, Michalski J, El-Naqa I, et al: Variation in the definition of clinical target volumes for pelvic node conformal radiation therapy of prostate cancer. Int J Radiat Oncol Biol Phys 69:S327, 2007

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