Predictive and Prognostic Factors for Non–Small Cell Lung Cancer—Potholes in the Road to the Promised Land

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Surgery offers the best chance of long-term cures for early-stage non–small cell lung cancer, the most common form of lung cancer. However, between one-third and one-half of early-stage tumors will relapse after curative intent resection. Adjuvant chemotherapy (ACT) offers a survival advantage for up to 15% of early-stage resected cancers and has become the standard of care. Thus, having the ability to select the minority of patients who are likely to benefit from ACT would be enormously beneficial to the majority of early-stage patients who undergo resection who could avoid experiencing the morbidity associated with ACT. This strategy would also create economic benefits in addition to the health benefits for patients. In this issue of the Journal, Chen et al. ( 1 ) present a microarray-based gene expression signature that has both prognostic and predictive values for early-stage non–small cell lung cancer.

Many markers have been tested for their predictive and prognostic value in lung cancer, and some have entered clinical practice. These include pathological typing that may be used to include or exclude certain forms of therapy—for example, adenocarcinoma histology is a strong predictor of outcome of pemetrexed therapy in advanced patients, and serious hemorrhagic complications may occur after bevacizumab therapy in patients with squamous histologies. Lung cancers are remarkably heterogeneous at the molecular level, and at least nine “driver” oncogene mutations have been described in lung adenocarcinomas ( 2 ). These mutations may lead to oncogene addiction, and effective therapies have been approved by the US Food and Drug Administration (FDA) for epidermal growth factor receptor mutations and ALK translocations, and many other individualized forms of therapy are currently in clinical trials ( 2 ). However, nearly half of lung adenocarcinomas and most of the squamous cell carcinomas lack known driver mutations.