Histologic Parameters Predicting Survival of Patients with Multiple Non-small Cell Lung Cancers

Abstract

The incidence of multiple lung cancers (MLCs) in patients with non-small cell lung cancer (NSCLC) has been reported to range from 3.7 to 8.0%, 1-5 and is constantly increasing due to the widespread use of computed tomography (CT) for screening of MLCs in lung cancer patients. In patients with MLC, distinguishing between intrapulmonary metastases and independent primary tumors is of great importance for determining tumor stage, patient prognosis and management, including the type of adjuvant chemotherapy. 6 In the revised 7th tumor, node and metastasis (TNM) staging system for lung cancer, separate tumor nodules in the same lobe were classified as T3 and nodules in different lobes as T4. These changes resulted in restaging of patients with MLCs from stage IIIB to stage IIB or IIIA, and from stage IV to stage IIIA or IIIB. Because patients with stage IIIB or stage IV NSCLCs are regarded as having poor prognoses, they are often treated with chemotherapy or chemoradiotherapy, but do not undergo surgical resection. Pathologic evaluation has been an important criterion for distinguishing intrapulmonary metastases from independent primary tumors. 6 In 1975, Martini and Melamed 7 developed clinicopathologic guidelines for the diagnosis of MLCs; these guidelines include determinations of tumor location, histologic type, lymphovascular invasion and foci of carcinoma in situ. However, these criteria cannot be completely applied to adenocarcinoma. More recently, several molecular methods, including mutational profiling and comparative genomic hybridization, have been used to evaluate the clonal relationships amongst multiple tumors. 8 These molecular methods, however, are neither cost- nor time-effective, and only a limited number of patients can be assessed by molecular tests during routine clinical practice. Diagnosis is therefore primarily based on the histologic characteristics of the tumors, such as histologic pattern, location, presence or absence of carcinoma in situ, vascular invasion, and other empirical features. Thus, a practically applicable and clinically relevant histologic approach is needed for appropriate management of patients with MLCs. We therefore analyzed the association between various histologic parameters, both individually and in combination, and clinical outcomes in patients with MLC to determine a practical method of subdividing patients into groups based on good and poor prognosis.