Lung cancer is the leading cause of cancer death in both men and women in the United States and worldwide. The American Cancer Society estimates approximately 234,000 new cases of lung cancer are diagnosed in the U.S. each year, with roughly 125,000 deaths. While these numbers are sobering, outcomes have improved markedly in recent years due to advances in targeted therapy, immunotherapy, and low-dose CT screening for early detection.

The two main categories of lung cancer—non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)—differ significantly in their behavior, treatment approaches, and prognosis. Understanding these distinctions is essential for patients and caregivers navigating a diagnosis.

Key Fact: The five-year survival rate for lung cancer has increased from 17% to over 25% in the past decade, driven primarily by targeted therapies for driver mutations (EGFR, ALK, ROS1, KRAS G12C) and immune checkpoint inhibitors. Patients diagnosed at a localized stage have a five-year survival rate of approximately 63%. (Source: ACS, SEER data)

Non-Small Cell Lung Cancer (NSCLC)

NSCLC accounts for approximately 80–85% of all lung cancers. It encompasses several subtypes that differ in their cell of origin and behavior:

Adenocarcinoma

The most common subtype of NSCLC, representing about 40% of all lung cancers. Adenocarcinoma typically arises in the outer regions of the lung and is the most common type found in non-smokers. It is more likely to harbor actionable driver mutations such as EGFR, ALK, ROS1, and KRAS G12C, making it amenable to targeted therapy.

Squamous Cell Carcinoma

Accounts for approximately 25–30% of NSCLC cases. Squamous cell carcinoma usually develops in the central airways of the lung and is strongly associated with smoking. It is less likely to have targetable mutations but often responds to immunotherapy.

Large Cell Carcinoma

A less common subtype (about 10% of NSCLC) that can appear in any part of the lung. It tends to grow and spread quickly. Large cell neuroendocrine carcinoma is a particularly aggressive variant.

Adenocarcinoma is the most common lung cancer subtype at 40%, followed by squamous cell carcinoma, SCLC, and large cell carcinoma.

Small Cell Lung Cancer (SCLC)

SCLC accounts for approximately 15% of all lung cancers and is almost exclusively associated with smoking. It is characterized by rapid growth and early metastasis. SCLC is typically classified into two stages:

Limited stage — Cancer is confined to one side of the chest and can be treated within a single radiation field. About one-third of SCLC patients present at this stage.
Extensive stage — Cancer has spread beyond one side of the chest to the other lung, distant lymph nodes, or other organs. About two-thirds of patients present with extensive-stage disease.

While SCLC is initially very responsive to chemotherapy and radiation, it frequently recurs. The addition of immunotherapy (atezolizumab or durvalumab) to first-line chemotherapy has improved overall survival in extensive-stage SCLC, marking the first advance in decades for this disease.

Risk Factors

Cigarette smoking — The leading risk factor, responsible for approximately 80% of lung cancer deaths. Risk increases with the number of cigarettes smoked per day and the number of years of smoking (measured in pack-years).
Secondhand smoke — Exposure to secondhand smoke increases lung cancer risk by 20–30%.
Radon exposure — Radon is the second leading cause of lung cancer. This naturally occurring radioactive gas can accumulate in homes and buildings. Learn about screening options.
Occupational exposures — Asbestos, diesel exhaust, arsenic, chromium, nickel, and other workplace carcinogens.
Prior radiation therapy — Previous chest radiation for other cancers increases risk.
Family history — A first-degree relative with lung cancer increases risk, even in non-smokers.
Air pollution — Long-term exposure to fine particulate matter (PM2.5) is an established risk factor.

Screening Saves Lives: The National Lung Screening Trial (NLST) demonstrated that annual low-dose CT screening reduces lung cancer mortality by 20% in high-risk individuals. The USPSTF recommends annual LDCT screening for adults aged 50–80 with a 20+ pack-year smoking history who currently smoke or quit within the past 15 years.

Lung Cancer Staging

NSCLC Staging (TNM System)

Stage	Description	5-Year Survival Rate
Stage I	Tumor confined to the lung, no lymph node involvement	~63%
Stage II	Tumor with ipsilateral hilar lymph node involvement or larger tumor invading local structures	~35%
Stage III	Locally advanced with mediastinal lymph node involvement or invasion of critical structures	~13–36% (IIIA vs IIIB/IIIC)
Stage IV	Distant metastasis (brain, bones, liver, adrenal glands, contralateral lung)	~7%

Survival rates from SEER data. Outcomes vary significantly based on molecular subtype and treatment response.

Five-year survival rates for NSCLC decrease significantly with advancing stage, from 63% at Stage I to 7% at Stage IV.

Treatment Options for NSCLC

Surgery

Surgical resection offers the best chance for cure in early-stage NSCLC (stages I–II and select stage IIIA). Procedures include:

Lobectomy — Removal of an entire lobe of the lung. This is the standard surgical approach and offers the best outcomes for most patients.
Segmentectomy or wedge resection — Removal of a smaller portion of the lung, used for small tumors or patients who cannot tolerate lobectomy.
Pneumonectomy — Removal of the entire lung, reserved for centrally located tumors that cannot be treated with lobectomy.

Minimally invasive approaches, including video-assisted thoracoscopic surgery (VATS) and robotic-assisted surgery, have reduced recovery times and complications compared to open thoracotomy.

Radiation Therapy

Radiation is used as definitive treatment for patients who are not surgical candidates, as adjuvant therapy after surgery, or as part of concurrent chemoradiation for locally advanced (stage III) disease. Stereotactic body radiation therapy (SBRT) delivers precisely focused high-dose radiation to small tumors and has shown excellent local control rates comparable to surgery for stage I NSCLC in medically inoperable patients. Learn more about radiation therapy.

Chemotherapy

Platinum-based doublet chemotherapy (cisplatin or carboplatin combined with another agent such as pemetrexed, paclitaxel, or gemcitabine) remains the backbone of systemic treatment for NSCLC without actionable driver mutations. Adjuvant chemotherapy after surgical resection of stage II–IIIA NSCLC improves five-year survival by approximately 5%. Learn more about chemotherapy.

Targeted Therapy

Molecular profiling of the tumor has transformed NSCLC treatment. The NCI recommends comprehensive biomarker testing for all patients with advanced non-squamous NSCLC. Key targetable alterations include:

EGFR mutations — Treated with tyrosine kinase inhibitors (TKIs) such as osimertinib (Tagrisso), which is now the preferred first-line agent with a median progression-free survival exceeding 18 months.
ALK rearrangements — Treated with ALK inhibitors including alectinib (Alecensa), brigatinib (Alunbrig), and lorlatinib (Lorbrena).
ROS1 rearrangements — Respond to crizotinib (Xalkori) and entrectinib (Rozlytrek).
KRAS G12C mutations — Sotorasib (Lumakras) and adagrasib (Krazati) are the first drugs to target this previously undruggable mutation.
Other targets — BRAF V600E, MET exon 14 skipping, RET fusions, NTRK fusions, and HER2 mutations all have approved or investigational targeted therapies.

Immunotherapy

Immune checkpoint inhibitors have become standard treatment for many patients with advanced NSCLC. These drugs block proteins (PD-1, PD-L1, CTLA-4) that prevent immune cells from attacking cancer:

Pembrolizumab (Keytruda) — Approved as monotherapy for NSCLC with high PD-L1 expression (TPS greater than or equal to 50%) or in combination with chemotherapy regardless of PD-L1 status.
Nivolumab (Opdivo) — Used alone or with ipilimumab (Yervoy) for advanced NSCLC.
Atezolizumab (Tecentriq) and durvalumab (Imfinzi) — Used in various settings including consolidation after chemoradiation for unresectable stage III NSCLC (durvalumab), where the PACIFIC trial showed a significant overall survival benefit.

Treatment Options for SCLC

SCLC treatment differs significantly from NSCLC due to its rapid growth and early dissemination:

Limited stage: Concurrent chemotherapy (cisplatin/etoposide) with thoracic radiation, followed by prophylactic cranial irradiation (PCI) to reduce brain metastasis risk. Selected patients may be surgical candidates.
Extensive stage: Chemotherapy (carboplatin/etoposide) plus immunotherapy (atezolizumab or durvalumab) is now the standard first-line regimen, based on the IMpower133 and CASPIAN trials.

Important: Second-line treatment options for SCLC remain limited. Lurbinectedin (Zepzelca) and topotecan are options for relapsed disease, but clinical trial participation should be strongly considered for patients with recurrent SCLC.

The Role of Biomarker Testing

The NCI and major oncology guidelines (NCCN) strongly recommend comprehensive molecular profiling for all patients with advanced NSCLC. Next-generation sequencing (NGS) can identify multiple actionable mutations simultaneously. PD-L1 testing by immunohistochemistry guides immunotherapy decisions. Patients should discuss biomarker testing with their oncology team before starting treatment, as results directly influence the treatment plan.

Clinical Trial Access: Lung cancer research is advancing rapidly, with hundreds of active clinical trials evaluating new therapies. The NCI maintains a searchable database of cancer clinical trials at cancer.gov/about-cancer/treatment/clinical-trials. Patients should ask their oncologist about applicable trials at every stage of treatment.

Medical Disclaimer: This information is intended for educational purposes only and should not replace professional medical advice. Treatment decisions should always be made in consultation with a qualified oncology team. Sources include the National Cancer Institute (cancer.gov), the American Cancer Society (cancer.org), and published clinical trial data.

Lung Cancer: A Comprehensive Treatment Guide