• © 2008 by American Society of Clinical Oncology

In Reply:

Our interpretation of the findings of the randomized European Organisation for Research and Treatment of Cancer (EORTC) trial 22911 that patients with positive surgical margins of their prostatectomy specimen—but not patients with negative margins—show a treatment benefit of adjuvant radiotherapy¹ is challenged in the letter to the editor by Dr Vikram in response to our article. In his opinion, it is likely that most participants of EORTC trial 22911 with a positive surgical margin of their prostatectomy specimen must have been treated immediately with androgen-deprivation therapy. Given that this therapy was not considered a violation of the trial protocol, he draws the conclusion that our data merely show that patients with a positive margin are more likely to receive androgen-deprivation therapy, implying that our data do not provide evidence for the selective benefit of adjuvant radiotherapy for this subset of patients.

Indeed, Dr Vikram is right with regard to his position that immediate androgen-deprivation therapy after prostatectomy, even in the absence of evidence of metastatic disease or biochemical progression, was considered as an end point in EORTC trial 22911. It should be obvious, however, that postoperative radiotherapy given to patients randomized to the intervention arm was not considered as an event at the time the radiation was initiated. Dr Vikram’s assumption, however, that it is (in Europe) common practice to treat patients with positive surgical margins of their prostatectomy specimen with androgen-deprivation therapy, is wrong.² Most urologists in Europe —and to our knowledge in North America³—would not consider treating a local problem (ie, positive surgical margins) with a potentially harmful⁴ and costly systemic therapy.

This view is further substantiated by the analysis of our patient data, revealing no more than four patients, including three patients in the nonintervention arm and one patient in the adjuvant radiotherapy arm, received androgen-deprivation therapy in the absence of progressive disease. This small number of patients did not significantly influence the outcome of our study.

We would also like to emphasize that the findings are derived from a randomly assigned trial, eliminating potential confounders, as mentioned by Dr Vikram, as they hold true for both trial arms; and the surgical margin status as reported originally by the local pathology was reversed in 30% of the cases by the review pathology on which our analysis was based.⁵ Thus, treatment decisions on the basis of surgical margin status at the time of the reporting of prostatectomy by the local pathology could not be influenced by the frequently discrepant findings at the time of pathology review.

We thank Dr Vikram for allowing us to clarify a potential source of confusion of our interpretation of the findings generated by the randomized EORTC trial 22911. We maintain our position that our data show that only patients with positive surgical margins of their prostatectomy specimen benefit from adjuvant radiotherapy, provided that a careful pathology examination of the specimen has been performed, using previously published strict criteria for surgical margin status.⁶