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Staging nodal disease in non-small cell lung cancer: implications for radiation therapy.

Data from recent trials have defined new standards of care for the treatment of stage III–N2 non-small cell lung cancer (NSCLC).1–3 For selected patients in whom a diagnosis of stage III–N2 disease was established preoperatively, chemoradiotherapy is not inferior to chemoradiotherapy and surgery2 or to chemotherapy followed by surgery.3 In view of its lower morbidity and mortality, chemoradiotherapy can be considered the standard treatment in patients presenting with stage III–N2 disease, even though locoregional control is suboptimal in nonsurgical treatment arms. Recent improvements in preoperative staging techniques, including the availability of multislice CT scans, positron emission tomography with 18-fluorodeoxyglucose (FDG-PET), and endoscopic techniques, have called into question the relevance of the present staging system, which was derived from analysis of a selected North American population.4 This analysis of the current nodal descriptors for NSCLC by the staging committee of the International Association for the Study of Lung Cancer (IASLC) at least partially answers these questions.5 The IASLC group developed and analyzed a truly international database consisting of 100,869 lung cancer cases managed within the time frame of 1990 to 2000. Of these, 38,264 cases with no evidence of metastatic disease after “clinical” N staging (which included a mediastinoscopy) and 28,371 surgically managed patients provided information on “pathologic” N staging. This analysis confirms the validity of the current nodal staging system in determining prognosis of patients with N2 or N3 disease. A major new finding is the identification of three distinct prognostic groups in patients undergoing resection without any induction therapy—namely, single-zone N1 disease, multiple-zone N1 or single N2 disease, and multiple-zone N2 disease. Observed differences in survival between surgical and nonsurgical stages in the analysis highlight, once again, the limitations of available noninvasive staging techniques. A major drawback of the present analysis is the absence of data relating to FDG-PET staging, a process that can exclude up to 30% of patients who are referred for radical radiotherapy.6 The resulting stage migration from exclusion of patients with distant metastases in this fashion will lead to a better survival in patients with stage III–N2 disease who are treated with chemoradiotherapy. Another limitation is the lack of data on the size of nodal masses, a factor that influences the likelihood of achieving a pathological complete remission with chemoradiotherapy. In the recent intergroup (INT) 0139 trial, pathological complete remissions were observed in 46% of mediastinal nodes treated using a preoperative induction chemoradiotherapy scheme to 45 Gy.2 Comparable data after high-dose chemoradiotherapy are limited for patients with NSCLC, but data from patients with head and neck cancers have revealed that post chemoradiotherapy nodal control rates were 91% at 2 years when nodal volumes were 3 cm; this decreased to 64% for nodal masses 3.0 cm (p 0.021).7