Lung Cancer: 5 Things to Know

Lung cancer is the second most commonly diagnosed cancer worldwide and remains the leading cause of cancer-related mortality, responsible for over 1.8 million deaths annually. In the United States alone, the American Cancer Society estimates that nearly 226,650 new cases will occur in 2025. Despite decades of public health campaigns and reductions in smoking rates, the global burden remains high owing to aging populations, environmental exposures, and rising incidence among never-smokers.

While tobacco smoke accounts for approximately 80%-90% of cases, other significant risk factors include radon exposure, occupational carcinogens such as asbestos and diesel exhaust, and air pollution, which the World Health Organization now classifies as a Group 1 carcinogen. Genetic predisposition and family history also contribute, particularly in younger individuals and those without traditional risk factors. Increasing recognition of lung cancer in never-smokers — now comprising up to 25% of cases worldwide in some regions — has driven research into molecular drivers, including epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) alterations.

Lung cancer often remains asymptomatic in early stages, with symptoms such as cough, weight loss, hemoptysis, or dyspnea appearing only once the disease is advanced. This delay contributes to the fact that nearly 60% of patients are diagnosed at a stage where curative surgery is no longer an option. Five-year survival rates vary dramatically by stage, ranging from approximately 65%-70% for localized disease to less than 10% for metastatic cases, underscoring the importance of early detection.

Treatment strategies have evolved from a “one-size-fits-all” approach to highly individualized care driven by histologic subtype, molecular profiling, and stage at diagnosis. Multidisciplinary management — including medical, surgical, and radiation oncology — remains essential.

Advances in supportive care, including the integration of palliative services and the management of treatment-related toxicities, have also improved the quality of life and outcomes for patients across all stages.

Here are five things to know about lung cancer.

1. Lung cancer encompasses diverse subtypes with distinct biology and behavior.

Lung cancer is broadly classified into two major categories: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC, which accounts for approximately 80%-85% of cases, encompasses adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Adenocarcinoma is the most common subtype overall and often arises in peripheral lung regions, with a higher prevalence in women and nonsmokers. Squamous cell carcinoma typically originates in the central bronchi and is strongly linked to tobacco use. Large cell carcinoma is less common but tends to grow and spread more quickly.

SCLC accounts for approximately 15% of lung cancers and is characterized by rapid growth and early metastasis; it is almost always associated with smoking and is often diagnosed at an advanced stage.

Other less common lung cancer types include carcinoid tumors, pleuropulmonary blastoma, and salivary gland-type lung carcinomas. Carcinoid tumors are a type of neuroendocrine tumor with typical and atypical subtypes and generally have a more indolent course compared with SCLC or NSCLC. Pleuropulmonary blastoma is a very rare, aggressive tumor that can occur in the lungs or pleura, primarily affecting young children. Salivary gland-type lung carcinomas are rare malignancies that include adenoid cystic carcinomas and mucoepidermoid carcinomas, which resemble their counterparts in salivary tissue and often require specialized histopathologic diagnosis.

Molecular characterization has revealed that even within NSCLC and SCLC, tumors are highly diverse, with actionable genetic alterations (eg, EGFR, ALK, ROS1) driving personalized treatment strategies and highlighting the importance of comprehensive testing at diagnosis.

2. Low-dose CT screening and emerging diagnostics are improving early detection.

Early detection is critical, as lung cancer survival rates are closely tied to stage at diagnosis. The 2025 National Comprehensive Cancer Network guidelines recommend annual low-dose CT screening for adults aged 50-80 years with a ≥ 20 pack-year smoking history who currently smoke or quit within the last 15 years. Low-dose CT reduces lung cancer mortality by up to 20%-24% in high-risk populations by detecting tumors at an earlier, potentially curable stage.

Robotic bronchoscopy enables safe sampling of small, peripheral nodules with high accuracy. Sputum cytology, percutaneous needle biopsy, and thoracentesis remain useful in specific contexts; advanced imaging modalities such as PET help define staging and guide treatment planning.

Artificial intelligence (AI) is increasingly integrated into screening and diagnosis, using deep learning and radiomics to detect subtle nodules, stratify risk, and reduce false positives. AI-assisted CT analysis has demonstrated sensitivities approaching 95% in early trials, with potential to standardize screening interpretation across centers.

3. Immunotherapy and targeted agents are redefining lung cancer treatment.

The therapeutic landscape for lung cancer has undergone significant changes over the last decade. Checkpoint inhibitors, such as pembrolizumab, nivolumab, and durvalumab, are now standard treatments for many NSCLC patients, both in advanced disease and as adjuvant or neoadjuvant therapies. In SCLC, the bispecific T-cell engager tarlatamab has emerged as a promising option in patients with progression after chemotherapy, demonstrating durable responses and improved survival compared with traditional chemotherapy in this situation.

EGFR inhibitors (eg, osimertinib, lazertinib) are standard for EGFR-mutated NSCLC and have shown significant progression-free survival benefit, including in patients with brain metastases. KRAS G12C inhibitors such as sotorasib offer the first targeted option for this previously undruggable mutation. ALK inhibitors, including alectinib and lorlatinib, are options for patients with ALK rearranged advanced lung cancer, and this typically affects younger patients with little or no smoking history. ROS1 inhibitors such as repotrectinib demonstrate strong intracranial activity, while c-Met inhibitors, such as telisotuzumab vedotin, are addressing MET-driven tumors.

Antibody-drug conjugates such as fam-trastuzumab deruxtecan (for HER2-mutated NSCLC) and datopotamab deruxtecan (for EGFR-mutated NSCLC post TKI treatment) are delivering chemotherapy payloads directly to tumor cells, reducing systemic toxicity and improving efficacy.

4. Advances in surgery and radiation are enabling less invasive, more precise treatment.

Surgery remains the primary curative option for early-stage lung cancer, with a trend towards lung-sparing procedures such as segmentectomy and wedge resection for small tumors. Robotic-assisted thoracoscopic surgery and video-assisted thoracoscopic surgery have minimized incision size, improved precision, and reduced recovery time compared with open thoracotomy.

Sleeve resection, a technique that preserves lung tissue while removing central tumors and rebuilding the bronchus, is being increasingly used in select patients to avoid pneumonectomy. Intraoperative imaging now enables real-time visualization of tumor margins, thereby increasing complete resection rates.

Stereotactic body radiation therapy delivers high doses over fewer sessions, offering a curative option for early-stage, medically inoperable patients. Intensity-modulated radiation therapy and proton therapy enable highly conformal dosing, reducing exposure to surrounding organs. Online adaptive radiotherapy, sometimes combined with immunotherapy, enables day-to-day adjustments to treatment plans, allowing for the account of tumor and anatomical changes, thereby optimizing outcomes.

5. Comprehensive genomic profiling is driving personalized therapy.

Comprehensive genomic profiling (CGP) has become a cornerstone of modern lung cancer care, enabling the simultaneous analysis of hundreds of genes to identify actionable alterations. FDA-approved panels such as FoundationOne CDx, FoundationOne Liquid CDx, and Guardant360 CDx are widely used to guide therapy selection in advanced disease.

CGP detects common mutations (EGFR, ALK, ROS1, KRAS, MET) and rare but targetable fusions (NTRK, RET). It also provides information on tumor mutational burden and microsatellite instability status, which can inform immunotherapy eligibility. New assays, such as DetermaRx, are moving into earlier-stage disease, quantifying gene expression to predict recurrence risk and potential benefit from adjuvant immunotherapy.

While access remains a challenge due to cost and tissue availability, the growing role of liquid biopsy and centralized testing is improving availability. As lung cancer becomes increasingly stratified by molecular subtype, CGP is critical for ensuring patients receive the most effective, individualized care.