[Letter] Re Kessler P et al. Neoadjuvant and adjuvant therapy in patients with oral squamous cell carcinoma. Long-term survival in a prospective, non-randomized study. Br J Oral Maxillofac Surg 2008; 46: 1-5.

This paper makes a very important claim in the current uncertainty over the best use of neoadjuvant therapy in the treatment of oral cancer. In the discussion the authors state, “The results of this study as far as the long-term survival is concerned have shown that neoadjuvant treatment should be preferred whenever the general health of the patient will allow.” It is disappointing that the authors have not acknowledged some important weaknesses in this study, which may put some doubt into the claim above. Our main concern is the presentation of the survival data, which does not address either the stage of the disease or the comorbidity and implies a considerable advantage for the neoadjuvant chemoradiotherapy group according to cumulative survival presented in Fig. 1. We find the survival figures difficult to interpret given the information on causes of death. The 4 patients who died during the preoperative chemoradiotherapy do not register on Fig. 1. One has to question tumour free-survival as the sole outcome measure and whether treatment-related death should also have been incorporated as an adverse event in the calculations. In the Kaplan-Meier survival graph the adjuvant arm shows an immediate drop of 2 or 3 patients which does not seem possible if all these patients had radiotherapy and the timing of the survival data was from the date of surgery. We also question the odd fall-off in the neoadjuvant line after 55 months. In the same way one has to question the accuracy of some of the survival estimates by T stage, e.g. a five-year survival of 83.1% for T1 tumours in the neoadjuvant group when the number of patients was only three! Reporting to one decimal place is false precision. If similar lengths of follow-up can be assumed, as the methods imply, then a simple percentage survival rate using the data from Table 5 makes for an interesting comparison: disease-specific survival for the neoadjuvant group but also including those 4 patients who died as a direct result of chemoradiotherapy is 82% (61/74)) compared to 83% (45/54) for the adjuvant arm. It should be acknowledged that the patients are poorly matched in terms of clinical stage of disease and co-morbidity. The authors state, “the size of the tumour had no influence on the treatment decision” and yet make no comment in the discussion on the unequal distribution of T1 tumours (33% (18/54) in the adjuvant group compared to 4% (3/74) in the neoadjuvant group). Deaths not related to the index disease or chemoradiotherapy are 11% (8/74) for the neoadjuvant group compared to 19% (10/54) in the adjuvant group. The management of oral cancer has been aggressive for a significant group of patients in this study. Most would question the use of ipsilateral modified radical neck dissection and contralateral suprahyoid neck for N0 disease. The failure to report the stage of disease treated means that we cannot know how many patients were stage I or II. All we can devise from the data is that 50 patients were T1 or T2 and 45 were N0. In most units these patients would not receive radiotherapy or chemoradiotherapy, as an adjunct to successful surgery. It is a significant oversight not to mention the papers by Cooper1 and Bernier2 reporting improved predicted survival for postoperative chemoradiotherapy. Surely there are advantages to performing surgery first in order to accurately stage the disease and plan the extent of adjuvant treatment more accurately. The fate of patients that require surgery and chemoradiotherapy must be carefully presented. There are serious inherent weaknesses in this study which compares two groups of poorly matched patients treated in different ways. The claim that a randomised study is unethical reflects the certainty of the group that neoadjuvant chemoradiotherapy is a superior treatment to postoperative radiotherapy and yet this claim is meaningless unless it is compared to postoperative chemoradiotherapy. This is especially important as postoperative treatment means that the pstage of the tumour is available which is the most accurate predictor of survival in the important decision on whether adjuvant treatment is required and then to what extent (radiotherapy or chemoradiotherapy).