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Uncertainties Regarding Pelvic Radiotherapy for Prostate Cancer

Department of Radiation Oncology, Columbia University College of Physicians and Surgeons, New York, NY

To the Editor:

I read with great interest the recent article published in the Journal of Clinical Oncology titled "Phase III Trial Comparing Whole-Pelvic Versus Prostate-Only Radiotherapy and Neoadjuvant Versus Adjuvant Combined Androgen Suppression: Radiation Therapy Oncology Group 9413." The RTOG should be congratulated for executing another excellent randomized trial in prostate cancer.

However, I have three concerns that make me hesitant to accept these results and apply them in practice. The first concern is regarding whether the groups were equally balanced for all the important prognostic factors. In particular, the Gleason score stratification is a concern. It is well established the Gleason scores 7 to 10 are a heterogeneous group of patients. If there was a significant imbalance with more Gleason score 7 patients (especially if they are 3 + 4) in the neoadjuvant hormone therapy plus pelvic radiotherapy groups compared with the other groups, this could explain the apparent advantage of this treatment arm. Information regarding the breakdown of the number of patients in each treatment group with each of the Gleason scores in the 7 to 10 range would help the readers critically assess this trial.

The second concern is what the differences in grade 2 acute and chronic toxicities were. It is reassuring to know that severe (grade 3 or higher) toxicities were not increased appreciably with pelvic radiotherapy. However, a significant increase in grade 2 toxicities, especially chronic ones, might have a significant impact on one's assessment of the risk-benefit ratio, given the current results. For example, would a 10% increase in chronic grade 2 gastrointestinal toxicity be worth a 7% increase in biochemical control/progression-free survival at 4 years without any benefit in overall survival? The authors should provide this information to allow the readers to assess the risk-benefit ratio more accurately.

The third concern I have is how to understand the underlying physiology of the benefit of neoadjuvant hormone therapy combined with pelvic radiotherapy. In particular, if neoadjuvant is superior to adjuvant hormone therapy, why is there no benefit to this treatment among the patients treated with neoadjuvant hormones followed by prostate-only radiotherapy? Similarly, why is there no benefit to pelvic treatment among patients treated with adjuvant hormone therapy? For example, if one posits that neoadjuvant hormone therapy is superior to adjuvant because of changes in the local milieu (eg, improved oxygenation, decreased repopulation, etc) of the prostate, this benefit should also apply to those treated to the prostate only following neoadjuvant hormone therapy. Similarly, if one posits that the benefit of neoadjuvant hormone therapy is the result of early systemic treatment, then patients treated with neoadjuvant hormone therapy and prostate-only radiotherapy again should benefit. Similar arguments could be advanced to suggest that pelvic radiotherapy should benefit patients whether they were treated with neoadjuvant or adjuvant hormone therapy. Without an underlying mechanistic explanation to the apparent special interaction between neoadjuvant hormone therapy and pelvic radiotherapy and without a benefit in the groups treated with only one of these two treatments compared to the group treated with neither, it is difficult to understand and accept these results.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

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• In Reply:
  Mack Roach, III
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