49. Adjuvant treatment to surgery: Is it still a place for radio-or chemotherapy?

The two metaanalysis conducted by the Cambridge group has cent the scene for adjuvant treatment as well as the pattern of failure analysis after surgery. In the pattern of failure analysis performed after a complete resection, local failure is a race event for pathological stage I and II disease (less than 10 %). In opposite, for stage III, local failure remains an issue due to the wide range of tumor extent, from resectable disease to unresectable tumor. In contrast, distant metastasis is a common problem with figures ranging from 20 to 50%. A last issue is certainly the problem of second cancer induced by a long history of tobacco smoking rising the question of chemoprevention.To prevent distant metastasis, a systemic treatment is the logical answer. The metaanalysis suggested a slight nonsignificant benefit for a sequential Cisplatine based chemotherapy. The recent American trial of Keller et al comparing postoperative radiotherapy to a combined chemo-radiotherapy approach did not showed any difference for stage III disease: the only important prognostic factor was the type of mediastinal exploration: sampling vs. radical dissection. Several trials are on going worldwide: Anita, ALPI, and IALT… The main characteristics of those trials are to include a cisplatine based chemotherapy program and a large number of patients. This implies necessary a low efficacy; a small difference is expected. Furthermore, the already published trials showed a low compliance to chemotherapy.Is the page turned for radiotherapy in a combined approach with surgery? In view of the available randomized trials and the recent metaanalysis, a quick answer is yes. Indeed, both observed either no effect or even a detrimental impact on survival. Nevertheless, those trials were performed during the last three decades, a period of many improvements in the knowledge of the disease, in imaging procedure, in surgery and in radiotherapy. Preoperative radiotherapy may increase the resectability rate in well-selected patient: some groups are still advocating this approach for superior sulcus tumor whereas many phase II and some phase III trials are combining radiation with chemotherapy in a preoperative settings. The data available suggested a higher rate of pathological complete response but also a slight increase in morbidity. In contrast, postoperative irradiation improves the local control especially for stage III disease: this was clearly demonstrated by the Lung Cancer Study group trial, the MRC trial and the Feng trial. Furthermore, we should remember that the PORT metaanalysis suggested a differential impact according to the tumor extent: the negative impact of postoperative radiation disappeared for stage III disease (a similar observation was made by Dautzenberg et al). One possible explanation is that the therapeutic effect of postoperative radiotherapy compensated the negative impact due to a poor radiation technique (large volume, high daily dose, and cobalt machines…). Both approaches imply to use a modern radiation technique minimizing the risk of inducing severe life-threatening late effects: this is especially the case for postoperative radiotherapy due to the already loss of lung function due to the surgery and a long history of tobacco abuse. This is probably the place for a conformal radiotherapeutic approach.The last issue concerns the management of patients after induction chemotherapy followed by surgery: the current approach is to reserve postoperative radiotherapy for incomplete resection or for persistent nodal disease. Probably, another important factor may be the presence or not of nodal capsular rupture. We are certainly lacking good data on the postresection management and outcome of those patients.In conclusion, radiation has still its place for stage III disease in a combined approach with surgery and chemotherapy providing the use of an adequate radiation technique