Lung cancer remains the leading cause of cancer mortality in the United States and worldwide by a large margin. In 2016, there was an estimated 243,820 new lung cancer cases in the United States, and there were over 162,510 deaths attributable to lung cancer.¹ Despite a very clear and well-established link between tobacco use and lung cancer, lung cancer mortality results in more deaths in the United States per year than breast, colon, prostate, and pancreas combined. One of the many hurdles in the successful treatment of lung cancer relates to the difficulty in early detection. Only 10% to 15% of all lung cancer patients have localized disease (clinical stage I or II) at the time of diagnosis. Conversely, close to two-thirds of newly diagnosed lung cancer patients have metastatic disease (stage IV) at their initial time of diagnosis.¹ The delay in identifying early-stage lung cancer poses a significant challenge in the treatment of this disease. This chapter focuses on the workup and treatment of stage I and II lung cancers, and the expected long-term outcomes for this group of patients.

Although the incidence of breast and prostate cancer remains much higher than that of lung cancer, the mortality from lung cancer for years has exceeded that of breast, prostate, and colon cancer combined.² As of yet, no single intervention or treatment has resulted in a significant reduction in the number of lung cancer cases or long-term survival. There is a modest improvement in survival in a select group of patients with stage IV lung cancer utilizing targeted molecular therapies. Unfortunately, the patients who are responsive to this type of treatment represent a minority of all lung cancer cases diagnosed. The modest success achieved reducing the number of lung cancer deaths is likely attributable to a slow decline in the use of tobacco in the United States. Although the primary cure for lung cancer remains surgical resection for early stage lung cancer, the percentage of patients who are cured (as defined by disease-free 5-year survival) remains poor.

The primary cause of lung cancer remains the ongoing use of tobacco, specifically cigarette smoking. Despite a modest reduction in the use of tobacco through a number of initiatives here in the United States, smoking rates continue to remain above targeted goals for reduction.³ It is estimated that 85% to 90% of all lung cancers are directly attributable to smoking. The remaining 10% to 15% of lung cancer cases may be attributable to radon gas, occupational exposures (arsenic, nickel), air pollution, radiation exposure, and sporadic genetic changes. Although asbestos exposure is most commonly associated with the development of mesothelioma, it is also well recognized that asbestos significantly contributes to the development of lung cancer as well, and the combination of asbestos exposure and cigarette smoke has a synergistic effect in lung cancer development. Since the early 2000s, there have been a number of advances in our understanding of the role genetic mutations play in cell signaling pathways, which lead to the development of lung cancer, specifically adenocarcinoma. The identification of mutations in signaling pathways such as EGFR, ALK, BRAF, ROS1, KRAS, and others has provided novel therapeutic targets for patients with otherwise unresponsive disease.

Lung cancers are historically classified as either non-small-cell lung cancers (80%) or small-cell lung cancers (20%). This is an important clinical distinction as small-cell lung cancer (SCLC) remains an aggressive malignancy rarely treated by surgical resection. Less than 5% of all SCLCs are surgically resectable at the time of diagnosis either due to local or distant metastasis, and overall survival for SCLC remains poor with approximately 80% of patients surviving less than 2 years, and less than 10% of patients surviving 5 years following their initial diagnosis.

Of the 80% of non-small-cell lung cancers (NSCLCs), almost equal proportions are made up of squamous cell lung cancer and adenocarcinoma. Less common types of primary lung cancers include carcinoid tumors (typical and atypical), large cell neuroendocrine tumors, sarcomatoid carcinoma, and more rare types such as mucoepidermoid tumors, adenoid cystic carcinoma, and myoepithelial carcinoma. In general, early-stage NSCLC is treated primarily through surgical resection following appropriate staging workup and preoperative assessment. In addition, there is a type of lung cancer characterized by slow and indolent growth, previously known as bronchioalveolar carcinoma (BAC). This group of lung cancers has more recently been renamed minimally invasive carcinoma (MIC) or adenocarcinoma in situ (AIS) based on defined characteristics. These cancers tend to be less aggressive and multifocal in nature, and treatment is focused on local excision. In some instances an isolated focus of adenocarcinoma may arise in the background of an MIC, in which case surgical lobectomy would be the appropriate treatment.

Most early-stage lung cancers are asymptomatic, and by the time symptoms are present often the tumor is at an advanced stage. For early stage, surgically resectable lung cancers, the widespread use of CT imaging for a variety of indications has increased the early detection of incidentally identified lung cancers. Clinical symptoms which may prompt or warrant CT evaluation include hemoptysis, worsening shortness of breath, effusion on chest x-ray, unresolving or recurrent pneumonia, and unexplained weight loss. Lung nodules or lesions identified on chest x-ray must be confirmed by chest CT. Typically a contrast chest CT is performed to help identify any suspicious hilar or mediastinal lymphadenopathy, as well as provide tumor size and additional information regarding clinical staging and resectability, particularly with hilar lesions adjacent to the pulmonary artery or veins. Lesions which are spiculated, lobulated, greater than 1 cm in size, and demonstrate documented interval growth on serial CT are concerning for a primary lung malignancy. Round, well-circumscribed lung lesions are more typical of metastasis or benign hamartomas. A solitary lung nodule which has failed to demonstrate any growth over a 2-year period of time is generally considered to be benign.

CT-guided needle biopsy of the lesion may be beneficial in guiding treatment recommendations, but is not necessary in the event the lesion is highly suspicious on imaging and is amenable to excision by video-assisted thoracoscopic surgery (VATS) at the planned time of surgical resection. However, in patients who are not deemed to be good surgical candidates or where a tissue diagnosis is desired in advance of treatment, a tissue diagnosis still should be obtained. Other methods to establish a tissue diagnosis include standard bronchoscopy with biopsy or electromagnetic navigational bronchoscopy with biopsy.

Positron emission tomography (PET) scans are very useful in staging primary lung cancers. The primary benefit of a PET scan lies in identifying regional or distant metastasis, either to the local lymph nodes or to more distant sites. Because of the limitations in visualizing brain metastasis due to the inherent activity present, PET scans may be of limited value in assessing for the presence of metastasis to this area. In situations where there is clinical concern for brain metastasis or if brain metastasis are suggested on the PET scan, a dedicated head CT or more commonly brain MRI, should be performed.

Prior to proceeding with therapeutic intervention, a clinical stage should be established based on the imaging and biopsy results available. In general, any PET-positive mediastinal lymph nodes, or lymph nodes exceeding 1 cm in size, should be further evaluated by tissue biopsy. In addition, evidence of suspicious hilar lymph node involvement (N1 nodes) should also prompt further investigation into the mediastinal lymph nodes in the event occult micrometastasis is present. Cancer involvement of the mediastinal lymph nodes dramatically alters the stage, and consequently treatment recommendations, for the patient. The location of hilar and mediastinal lymph nodes are well defined using the Mountain–Dresler classification system. This classification system is used to describe the locations of lymph nodes biopsied either during preoperative staging or at the time of surgical resection (Fig. 60-1). The presence of pleural fluid or pleural studding on preoperative imaging is a worrisome sign of pleural involvement and should also be investigated. The presence of pleural disease represents an advanced lung cancer (stage IV), and palliative chemotherapy would be the appropriate course of action with those findings. Although thoracentesis is a relatively noninvasive method to assess fluid cytology, a negative result does not completely eliminate the possibility of pleural involvement. Recurrence of a pleural effusion warrants continued concern for metastatic disease and additional investigational studies.