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The treatment of lung cancer is in constant evolution. As the leading cause of cancer-related deaths worldwide, this highly lethal malignancy presents numerous therapeutic challenges. This chapter focuses on patients with stage III and IV lung cancer or in other words, locally advanced and metastatic lung cancer. About 80% of patients with lung cancer develop non-small cell lung carcinoma (NSCLC) type histology and these are the patients upon which this chapter will focus. The remaining 20% develop small cell carcinoma, which when locally advanced, given current therapeutics, is a uniformly nonsurgical disease treated primarily with chemotherapy. Despite increasing resolution in diagnostic imaging and attempts to screen high-risk patients, 65% of NSCLC patients continue to present with advanced disease (stage III or higher).1 Nevertheless, this is a heterogeneous group of patients who require a spectrum of management strategies ranging from curative intent therapy to palliative care. The common thread within this spectrum is the added value of customized care that implements a multimodality approach. Advances in our understanding of lung cancer biology have led to the incorporation of targeted therapies that likely hold the greatest promise for improving outcomes in this patient population.2 Refinements in stereotactic radiotherapy protocols, aggressive multiagent chemotherapy regimens, advances in surgical technique and recovery have all contributed to improved survival from advanced lung cancer. However, in many clinical scenarios the ideal combination of these modalities and their timing remains to be determined. This chapter summarizes the state of the art in the care of advanced NSCLC with the understanding that several areas remain controversial and that the coming years will bring significant changes leading to improved outcomes for this vulnerable population.


Despite reduced rates of smoking in the general population, lung cancer remains the most common malignancy.1 In the United States, it is the leading cause of cancer death with 228,190 new cases and 159,480 deaths estimated in 2013 representing 27.5% of all cancer-related deaths. Indeed, despite improvements in care, lung cancer portends a very poor prognosis with a mere increase in 5-year survival from 11.4% in 1975 to 17.3% in 2005. The poor survival rates are largely related to the high frequency of lymph node spread and metastatic disease present at the time of diagnosis. Although regionalized disease can still be cured, with 5-year survival rates in the vicinity of 26%, metastatic disease is virtually incurable with 5-year survival rates of 3.9% based on most recent data.1 When seen from this perspective, treatment of advanced lung cancer may seem almost futile; however, several specific clinical scenarios provide the opportunity for cure with current management strategies. Palliation when cure is not realistic remains of utmost importance. Moreover, with such bleak results the opportunities for significant progress and quantum leaps in survival from this aggressive disease are abundant.


As can be deduced from the high proportion ...

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