Molecular biologic staging and selection of therapy for non-small cell lung cancer

The optimal staging system achieves accurate assessment of extent of disease, effective prognostic stratification, and selection of appropriate therapy. The staging system for non-small cell lung cancer (NSCLC) provides a framework for the assessment of prognosis and the assignment of therapy for all patients with a new diagnosis of lung cancer, the most common cause of death by malignancy1. The most recent revision of the lung cancer staging system, which considers the size and location of the primary tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastases (M), is based on the analysis of a collected database representing all clinical, surgical-pathologic, and follow-up information for 5,319 patients treated for primary lung cancer2. Similar results have been reported among a population of 6,670 patients treated in Japan3. The power of these large databases in predicting prognosis is self-evident. Nevertheless, there is an inherent inaccuracy of this staging process. According to the TNM system, the predicted 5-year survival after complete resection for T1N0M0 NSCLC (stage IA) is only 67%2. Therefore, 33% of patients with stage IA NSCLC are incorrectly staged at presentation. Even with optimal therapy, these patients will succumb to their disease, predominately from the development of metastatic disease not detected at the time of diagnosis and initial therapy, despite the use of standard staging procedures4. Similarly, a significant fraction of all patients with Stage Ib or II disease are incorrectly staged, resulting in inaccurate assessment of extent of disease, prognostic stratification, and selection of therapy. Currently, adjuvant chemotherapy has been established as beneficial for selected patients with after complete resection5-7; however, the majority of patients will not benefit, from its administration: substantial fractions will die despite chemotherapy or would have survived even without chemotherapy. Molecular biologic staging refers to the assessment tumor markers associated with various oncogenic mechanisms in order to improve the risk stratification provided by conventional TNM staging. Biologic staging may target oncogenes, oncogenic protein products, growth factors, or receptors. The biologic techniques utilized include analysis of DNA, RNA, or protein products. Molecular biologic staging may potentially be applied to the primary tumor, lymph nodes, bone marrow, or serum, in order to establish the diagnosis of malignancy at earlier stage, to assess prognosis, to detect occult metastases, to select therapy, and to predict chemotherapy sensitivity or resistance. The purpose of the assessment of prognostic markers in the primary tumor is to identify patients, or groups of patients, with early stage disease, whose risk of recurrence is sufficiently high enough to justify adjuvant therapy. In addition, the assessment of the primary tumor may also enable more accurate selection of adjuvant therapy, either cytotoxic chemotherapy or targeted therapy. Assessment of lymph nodes may allow identification of micrometastatic disease: occult metastases not identified on routine pathologic examination. Correct assessment of micrometastatic lymph node involvement improves assessment of extent of disease, prognostic stratification, and choice of adjuvant therapy8. Assessment of bone marrow and serum may identify evidence of occult distant metastatic disease (Stage IV). Identification of these patients would prevent unnecessary surgical resection and allow patients to receive systemic therapy sooner. Copyright © 2007 JMS.

Duke Scholars

Author Thomas Anthony D'Amico Surgery, Cardiovascular and Thoracic Surgery