Patients with stage I non-small cell lung carcinoma at postoperative rise for local recurrence, distant metastasis, and death: Implications related to the design of clinical trials

Purpose: Patients with pathologically staged American Joint Committee on Cancer stage I (T1 N0 or T2 N0) non-small cell lung cancer have a favorable prognosis after complete surgical resection compared with patients with more advanced stages. Benefits of adjuvant therapy in this setting are unproved. However, there may be subgroups of patients with stage I disease at high enough risk for local recurrence to prompt consideration of adjuvant or neoadjuvant radiation therapy. Likewise, there may be subgroups of patients at high enough risk for distant metastasis to justify the evaluation of chemotherapy. Methods and Materials: From 1987 through 1990, 370 patients undergoing gross total resection of non-small cell lung cancer had stage I disease and received no chemotherapy or radiation therapy as part of their primary treatment. These patients were the subject of a retrospective review to separate patients into high-, intermediate-, and low-risk groups with respect to freedom from local recurrence (FFLR), freedom from distant metastasis (FFDM), and overall survival by using a regression tree analysis. Results: The 5-year rates of FFLR, FFDM, and survival were 85%, 83%, and 66%, respectively. Regression analyses revealed that the factors independently predicting for a poorer FFLR rate included fewer than 15 lymph nodes dissected and pathologically evaluated (p = 0.002) and the presence of a T2 tumor (p = 0.04). Factors independently predicting for a poorer FFDM rate included a maximal dimension greater than 5 cm (p = 0.02) and nonsquamous histology (p = 0.03). Factors independently predicting for a poorer survival rate included fewer than 15 lymph nodes dissected and pathologically evaluated (p = 0.001) and a maximal dimension greater than 3 cm (p = 0.003). Regression tree analyses were used to separate patients into risk groups. Conclusion: Incorporating the aforementioned factors into regression tree analyses, three risk groups were identified with respect to FFLR. Two each were identified for FFDM and for survival. For each of these three end-points, the differences in outcomes for each risk group were found to be both statistically and clinically significant. These risk groups may be useful in the future design of phase III trials evaluating the use of adjuvant chemotherapy and radiation therapy in the stage I setting. (C) 1999 Elsevier Science Inc.