Lung Cancer

Epidemiology and Etiology

Lung cancer is the most common cause of cancer death in the US, with an estimated 135,720 deaths in 2020.¹ Smoking is the strongest risk factor for lung cancer, with over 90% of cases being tobacco-related.

Pathology

Non-small-cell lung cancer (NSCLC) accounts for gt;85% of cases. The most common histologic subtypes are adenocarcinoma and squamous cell carcinoma. Small-cell lung cancer (SCLC) is associated with rapid tumor growth and early development of metastases compared to NSCLC.

Screening

Lung cancer screening with low-dose computed tomography (LDCT) reduces lung cancer mortality and the U.S. Preventive Services Task Force (USPSTF) currently recommends annual screening for lung cancer with LDCT in current smokers or former smokers who quit within the past 15 years, are between 50 and 80 years old, and have a #8805;20-pack-year smoking history.

Clinical Presentation

• Patients with early-stage disease are often asymptomatic. However, when present, symptoms may be related to local disease (cough, dyspnea, hemoptysis), intrathoracic extension (hoarseness from recurrent laryngeal nerve involvement, dysphagia, chest wall pain, Horner syndrome, brachial plexus involvement, superior vena cava [SVC] syndrome), systemic metastases (fever, jaundice, bone pain, headaches), or paraneoplastic syndromes.

• Paraneoplastic syndromes in lung cancer typically include hypercalcemia (humoral or osteolytic), hyponatremia from syndrome of inappropriate antidiuretic hormone, and hypertrophic pulmonary osteoarthropathy.

Diagnostic Testing

• Any patient with a smoking history and concerning pulmonary symptoms should undergo a CT scan of the chest. A normal chest radiograph (CXR) does not exclude lung cancer.

• Staging evaluation in all patients should include a CT scan of the chest and abdomen. Additional imaging depends on the initial findings. In potentially curable patients, the evaluation also typically includes a brain magnetic resonance imaging (MRI), positron emission tomography (PET) CT scan, and mediastinoscopy.

Staging

TNM: T1 (tumors #8804;3 cm), T2a (gt;3 but #8804;4 cm), T2b (gt;4 but #8804;5 cm), T3 (gt;5 but #8804;7 cm or separate nodules in the same lobe, or invasion of chest wall, pericardium, or phrenic nerve), T4 (gt;7 cm or tumor nodules in an ipsilateral different lobe or invasion of other structures including mediastinum, heart, trachea, spine, esophagus, recurrent laryngeal nerve), N0 (no lymph node involvement), N1 (ipsilateral pulmonary or hilar lymph nodes), N2 (ipsilateral mediastinal lymph nodes), N3 (supraclavicular or contralateral lymph nodes), M0 (no metastases), M1a (pleural or pericardial nodules or effusion, separate nodule(s) in the contralateral lung), M1b (single extrathoracic metastasis), M1c (multiple extrathoracic metastases). Stage: I (T1-T2aN0M0), IIA (T2bN0M0), IIB (T3N0M0 or T1-2N1M0), IIIA (T1-2N2M0, T3N1M0, or T4N0-1M0), IIIC (T3-4N3M0), IVA (T1-4N1-3M1a-M1b), IVB (T1-4N1-3M1c).

TREATMENT

Non-Small-Cell Lung Cancer

• Stages I, II, and selected IIIA: Surgery is the preferred therapy. Adjuvant platinum doublet chemotherapy improves overall survival in patients with surgically resected stage II and III NSCLC. Adjuvant therapy with osimertinib for 3 years is approved for patients with EGFR-mutated NSCLC.² Radiation therapy, with or without chemotherapy, is an option for those who decline or are not candidates for surgical resection.

• Stage III: The standard therapy is with concurrent chemoradiation followed by consolidation durvalumab for 1 year. Surgery is indicated in select patients.

• Stage IV (metastatic): Therapy is administered with palliative intent, and choice of therapy is guided by presence of targetable alterations (EGFR, ALK, ROS1, ERBB2, BRAF, KRAS, MET, RET, and NTRK), PD-L1 expression of the tumor as measured by IHC, histology, and patient performance status.^3,4

î Several ICIs have been approved for the treatment of NSCLC, in the first-line setting alone or in combination with chemotherapy, including nivolumab with or without ipilimumab, pembrolizumab, or atezolizumab.

#9632; Pembrolizumab or atezolizumab monotherapy has been shown to be superior to chemotherapy alone in patients whose tumors show gt;50% PD-L1 expression.

#9632; Combining pembrolizumab with platinum doublet chemotherapy (pemetrexed for nonsquamous, paclitaxel or albumin-bound paclitaxel [nab-paclitaxel] for squamous) has been shown to be superior to chemotherapy alone, regardless of tumor PD-L1 status.

î There are several effective medications for patients with specific genomic alterations:

#9632; EGFR mutation: Osimertinib, gefitinib, erlotinib, afatinib, dacomitinib

#9632; ALK rearrangements: Alectinib, crizotinib, ceritinib, lorlatinib, and brigatinib

#9632; KRAS G12C mutation: Sotorasib

#9632; ROS1 rearrangements: Crizotinib, entrectinib, and lorlatinib

#9632; MET exon 14 mutation: Crizotinib, capmatinib, and tepotinib

#9632; BRAF V600E mutation: Dabrafenib alone or in combination with trametinib

#9632; RET rearrangements: Selpercatinib, pralsetinib, and cabozantinib

#9632; NTRK gene fusions: Larotrectinib and entrectinib

Small-Cell Lung Cancer

• Stages I to III (limited stage): The standard therapy includes concurrent chemoradiation with a platinum agent (carboplatin or cisplatin) plus etoposide followed by prophylactic cranial irradiation (PCI).

• Stage IV (extensive stage): Chemotherapy is the preferred therapy, usually with a platinum agent (cisplatin or carboplatin) plus etoposide and a PD-L1 inhibitor (atezolizumab or durvalumab). The role for PCI in patients with stage IV disease is not clearly defined.

• Second-line therapies for recurrent disease may include topotecan, lurbinectedin, irinotecan, paclitaxel, docetaxel, and temozolomide.