Occult Nodal Metastasis in Non–Small-Cell Lung Cancer: Implications for the Radiation Oncologist

Abstract

TO THE EDITOR: We congratulate Rusch et al for performing the well-designed and thought-provoking ACOSOG (American College of Surgeons Oncology Group) Z0040 trial, which was recently reported in Journal of Clinical Oncology. In their study, occult nodal metastasis was detected in 22% of patients with histologic N0 disease and associated with decreased disease-free and overall survival. These findings are consistent with prior reports from other groups. Rusch et al correctly indicate that immunohistochemical evaluation of lymph nodes should be incorporated into future trials of adjuvant chemotherapy. We wish to point out that the presence of occult nodal disease may also have implications in decisions regarding postoperative radiotherapy. After initial treatment with complete surgical resection, National Comprehensive Cancer Network guidelines recommend postoperative radiotherapy for patients with N2 disease but not for patients with N0 to N1 disease. These recommendations are largely based on trials using outdated techniques, nonrandomized comparisons, and retrospective reviews. Further study is required to define optimal treatment algorithms when modern staging procedures, surgical techniques, systemic therapy, and radiotherapy are available. The ongoing Lung ART (Lung Adjuvant Radiotherapy Trial) study is re-examining the role of adjuvant radiotherapy for N2 disease. A recent review of patients with non–small-cell lung cancer with pathologic N1 disease showed that the thorax was the most common site of initial disease progression, especially for patients who received systemic therapy. This suggests that adjuvant radiotherapy may be worth revisiting in the setting of N1 disease as well. An analysis of failure patterns in ACASOG Z0040 would be of great interest. If occult nodal metastasis were associated with increased risk of locoregional failure, it would strengthen the case for studying adjuvant radiotherapy in selected patients. Occult nodal metastasis could theoretically be associated with a subtype of non– small-cell lung cancer that preferentially spreads via regional lymphatics. This is supported by the fact that no association between occult lymph node metastasis and occult bone marrow involvement was detected in ACASOG Z0040. Thus, identification of occult nodal disease might help identify patients who are likely to benefit from postoperative radiotherapy.