Chapter 18: Non–Small Cell Lung Cancer

INTRODUCTION

Lung cancer is the third most commonly diagnosed cancer, after breast and prostate cancers, but it is the most common cause of cancer-related death (¹). Every year, 1.5 million patients die of lung cancer worldwide (¹). About 70% of patients will be diagnosed with advanced stages that are not amenable to curative therapies. Only 15% of all patients diagnosed with lung cancer are alive 5 years after diagnosis.

Lung cancer is broadly divided into small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC). Approximately 85% of lung cancer is NSCLC. This chapter briefly describes the epidemiology, etiology, histology, prevention, and molecular biology of NSCLC. The major focus will be clinical presentation, diagnosis, staging, and treatment based on current clinical knowledge, with an emphasis on our approach at the University of Texas MD Anderson Cancer Center (MDACC).

EPIDEMIOLOGY

Lung cancer is rarely diagnosed in people younger than 35 years old. Incidence and death rates rise exponentially until age 75, when a plateau is reached. Non–small cell lung cancer accounts for the greatest number of deaths from cancer in both men and women over age 60.

The geographic, social, and temporal trends of the incidence of NSCLC are closely related to tobacco consumption. In developed Western countries, the incidence of NSCLC has been declining; however, it has been increasing in Asia, Eastern Europe, and developing countries (¹).

Worldwide, NSCLC is more common in men, and this difference has been attributed to higher tobacco consumption. In some regions, like Eastern Europe and South America, there was an uptake of smoking by women in the 1980s, and these areas are currently experiencing a rise in NSCLC cases in women. In the United States, the incidence has been declining for both men and women as tobacco use declines; the male-to-female ratio from 2007 to 2011 was 1.4:1 (²).

There is some evidence that African Americans might be more susceptible to the carcinogenic effects of tobacco smoke (³); however, smoking behaviors might also account for socioeconomic and racial differences in lung cancer incidence.

ETIOLOGY

Smoking

The causal relationship between tobacco smoke and lung cancer was established in the 1950s in case-control and cohort studies. This led to the 1964 report of the US Surgeon General, concluding that smoking can cause lung cancer. Currently, it is estimated that 85% to 90% of lung cancers are due to smoking. Nonsmokers who are exposed to secondhand smoke are also at an increased risk. There is a dose-response relationship between smoking and lung cancer risk, and smoking cessation leads to a significant risk reduction (Table 18-1) (⁴).