Lung cancer is the leading cause of cancer death in the United States, accounting for about one quarter of cancer deaths, and more than a quarter of million lung cancer diagnoses are projected in the United States for 2020. Lung cancer has various types, pathologies, and histologies, each with its own prognosis and treatment plan. Non-small cell lung cancer (NSCLC) consists of about 80%–85% of lung cancer diagnoses.

Prevention and Screening

Men and women carry a 1 in 15 and 1 in 17 risk of a lung cancer diagnosis, respectively. That statistic includes smokers, although the risk is greater among smokers than nonsmokers.

Exposure to tobacco smoke is the most prevalent risk factor for developing NSCLC, and smoking cessation is the top prevention method for high-risk patients. Vaping is a new challenge, especially regarding its yet-to-be-identified long-term risks. Although vaping products are labeled as tobaccoless, research has not yet shown whether their aerosol and vapors are carcinogens, but they are known irritants associated with lung disease and pathology.

Occupational and environment exposure to chemicals such as radon and asbestos are other risks. Certain nonmodifiable risk factors include prior irradiation to the chest, pollution, and a family history of lung cancer.

The U.S. Preventive Services Task Force (USPSTF) recommends that high-risk patients receive screening through low-dose computed tomography (CT) scans. Patients aged 55–80 who are either current heavy smokers or who quit with a 15 years should receive screening, but they can stop after age 80 or 15 years after smoking cessation. USPSTF defines “heavy” smoking based on patients’ pack history. Data suggest that low-dose CT scan screening may promote early diagnosis and improve death rates.

Biomarkers  

Biomarker testing of lung tissue and peripheral blood (i.e., liquid biopsy) is critical for treatment selection. Because so many somatic oncogenic gene variants have approved treatments, tests should involve a broad panel of genes rather than a single-gene approach.

EGFR, ALK, ROS1, BRAF, NTRK, PD-L1, and KRAS biomarkers are relevant in NSCLC and should be tested for appropriate biomarker-guided treatment. KRAS somatic variants are common in NSCLC, especially in smokers, but are less actionable. Other emerging biomarkers include RET, MET exon 14 skipping variant, ERBB2 (HER2), and tumor mutational burden.

Treatment

Treatment options depend on extent of disease at diagnosis and whether lymph nodes or distant metastasis are involved. It usually consists of multimodalities, including radiation, and systemic chemotherapy and targeted agents. Immunotherapy agents have a growing role in treatment plans as well. For some early-stage localized tumors, surgical intervention may be an option.

Radiation is used in the adjuvant and neoadjuvant setting to shrink tumors prior to chemotherapy or kill remaining cells after surgery. Despite numerous advancements in targeted and immunotherapy, systemic chemotherapy remains the mainstay of NSCLC treatment. In many cases, combination regimens that involve platinum-based agents are first-line therapy. Other options include gemcitabine, protein-bound paclitaxel, and pemetrexed.

A growing number of targeted agents are being used alone and in combination with other treatment modalities. Among the most common are angiogenesis inhibitors (i.e, bevacizumab and ramucirumab) and EGFR inhibitors (i.e., erlotinib and afatinib). Additional tumor targets and proteins are being studied.

Immunotherapy, used either alone or as part of combination regimens, has changed the face of lung cancer treatment, adding to the previous short list of treatment options and improving patient outcomes. Multiple checkpoint inhibitors have approved indications for NSCLC, some even as first-line therapy in combination with other agents. A patient’s candidacy for the therapy depends on their PD-1 and PLD-L1 tumor receptor status.

Because NSCLC is an aggressive cancer, palliative care should be integrated throughout treatment. The disease is often associated with a collection of malignant fluid that may result in a pleural or pericardial effusion. Patients may require intermittent fluid draining or need a permanent catheter to remove accumulated fluid.

Common Side Effects and Management

Platinum-based chemotherapy agents carry dose-limiting toxicities such as myelosuppression (carboplatin and cisplatin), nephrotoxicity (cisplatin), and peripheral neuropathy (oxaliplatin). Cisplatin and some other treatments are highly emetogenic.

Targeted agents have different side-effect profiles than cytotoxic chemotherapy, which vary based on the targeted approach of each agent. EGFRs, for example, are highly associated with skin reactions and diarrhea, whereas angiogenesis inhibitors are linked to circulatory issues, including hypotension and poor wound healing. Checkpoint inhibitors for NSCLC are associated with fatigue and immune-related adverse events, including pneumonitis, colitis, dermatitis, hepatitis, and endocrinopathies. Severity may be increased when using couplet checkpoint blockade. Targeted therapy-induced symptoms cannot be treated in the same way as chemotherapy-induced symptoms.

Survivorship

Survivors should be educated about the importance of smoking cessation in preventing recurrence. Other topics of focus include optimizing quality of life and preventing secondary or other primary cancers. Depending on a patient’s treatment plan, they may need to manage reduced lung capacity, peripheral neuropathies, chronic inflammation, or endocrinopathies. Individualized survivorship care plans are instrumental in facilitating interprofessional communication and optimizing survivors’ primary care.