Lung Cancer: Symptoms, Stages, and Treatment
In this article
What Is Lung Cancer?
Lung cancer is a malignant disease that develops when cells in the lungs multiply uncontrollably. Worldwide, it is both the most common cancer and the leading cause of cancer-related death. The situation is no different in Türkiye: according to the latest data, lung cancer is both the most common cancer type and the leading cause of cancer-related death in our country. This guide provides a comprehensive discussion of the causes and symptoms of lung cancer, diagnostic and staging methods, current treatment options, and the diagnosis and treatment process in Türkiye, based on current literature.
The lungs are a pair of sponge-like organs located on either side of the heart within the chest. They allow inhaled oxygen to pass into the blood and carbon dioxide in the blood to be expelled. The right lung consists of 3 lobes and the left lung of 2 lobes. Lung cancer most often arises from the epithelial cells lining the airways. As it grows, it can spread (metastasize) to neighboring tissues, lymph nodes, and, through the bloodstream, distant organs such as the brain, liver, bones, and adrenal glands.
How Common Is Lung Cancer? (Current Statistics)
According to the latest global cancer statistics (GLOBOCAN 2024), published in 2026, approximately 2,64 million new cases of lung cancer occur worldwide each year (12,8% of all cancers), and lung cancer causes 1,86 million deaths. This figure represents 19,1% of all cancer-related deaths, making lung cancer the leading cause of cancer-related death worldwide — ranking 1st in both incidence and mortality among men and 2nd among women, after breast cancer.
In Türkiye, the situation is even more severe than the global average: according to IARC's Türkiye country fact sheet, updated in July 2026, and its GLOBOCAN 2024 estimates , approximately 37.800 new cases of lung cancer are reported each year (16% of all cancers), and lung cancer causes approximately 31.700 deaths. This represents 27,8% of all cancer-related deaths — substantially above the global average of 19,1%. Lung cancer ranks 1st in Türkiye in both incidence and mortality. The most important reason for this high rate is the high prevalence of smoking in our country.
An important trend attracting attention in recent years is the rising incidence of lung cancer among people who have never smoked, particularly women. In countries such as the United States and the United Kingdom, approximately 15-20% of lung cancer deaths occur among people who have never smoked. In parallel with this change, adenocarcinoma is now the most common lung cancer subtype (46% in men and 60% in women) — a histological type with a weaker association with smoking than other types.
Types of Lung Cancer (NSCLC / SCLC)
Lung cancers are divided into two main groups according to their microscopic (histological) appearance:
It accounts for the vast majority of all lung cancers (approximately 77% according to current data). It is most commonly divided into three subtypes: adenocarcinoma (the most common type, also common in people who do not smoke), squamous cell carcinoma (strongly associated with smoking, generally in the central regions of the lung), and large cell carcinoma (rarer). NSCLC differs substantially from SCLC in terms of treatment approach and targeted therapy options.
It accounts for approximately 13% of all lung cancers (although the conventional figure is "15%", current data show that this proportion has declined slightly). Its association with smoking is even stronger than that of NSCLC; nearly all patients have a smoking history. It grows much faster and has a strong tendency to spread to distant sites even at an early stage; treatment therefore relies more on chemotherapy and immunotherapy than on surgery.
The remaining approximately 10% includes rarer subtypes, such as carcinoid tumors. Readers wishing to learn more about the differences between NSCLC and SCLC can see our article Small Cell and Non-Small Cell Lung Cancer: What Are the Differences? for further details.
Risk Factors
The vast majority of lung cancer cases (more than 40% of cancers in men in Türkiye) are associated with smoking and tobacco products. The risk increases in direct proportion to the amount and duration of smoking; quitting smoking gradually reduces the risk over the years after cessation.
The main risk factors other than smoking are:
- Exposure to passive (secondhand) tobacco smoke
- Exposure to radon gas — particularly in enclosed, poorly ventilated homes
- Occupational exposures — prolonged exposure to substances such as asbestos, arsenic, chromium, nickel, and diesel exhaust
- Air pollution — particularly exposure to fine particulate matter (PM2.5)
- Family history and genetic predisposition — a history of lung cancer in first-degree relatives increases the risk
- Previous lung diseases — chronic lung diseases such as COPD and pulmonary fibrosis
- Previous radiotherapy to the chest
The causes of lung cancer in people who have never smoked have a different profile; on this subject, you can read our article Causes of Lung Cancer Other Than Smoking and, for the health effects of quitting smoking, our article How Do the Lungs Recover After Quitting Smoking? provides further information.
What Are the Symptoms of Lung Cancer?
Lung cancer often causes no symptoms at an early stage; unfortunately, most cases are therefore diagnosed at an advanced stage. A doctor should always be consulted if one or more of the following symptoms persist for longer than two weeks:
- A persistent cough lasting longer than two weeks
- Coughing up blood-stained sputum (hemoptysis)
- Chest pain — particularly pain that worsens with deep breathing, coughing, or laughing
- Hoarseness
- Unexplained weight loss and loss of appetite
- Shortness of breath
- Fatigue and weakness
- Recurrent lung infections (bronchitis, pneumonia)
- Wheezing
- New or worsening breathlessness
These symptoms are not specific to lung cancer; they can also occur in many benign respiratory diseases. However, prompt evaluation is important when these symptoms occur, particularly in people with a smoking history or those over 50 years of age.
Early Detection: Lung Cancer Screening
One of the greatest problems with lung cancer is that it has often reached an advanced stage by the time symptoms appear. Regular screening in high-risk people who do not yet have any symptoms therefore significantly increases the chance of detecting the disease at an early, treatable stage.
According to the United States Preventive Services Task Force (USPSTF) guideline updated in 2021 and still current as of 2026, people who meet all of the following three criteria are recommended to undergo annual low-dose computed tomography (low-dose CT) screening:
- Age: Between 50-80 years of age
- Smoking history: A smoking history of at least 20 pack-years (pack-years = number of packs smoked per day × number of years of smoking)
- Smoking status: Currently smoking or having quit within the past 15 years
Screening is discontinued once a person has not smoked for 15 years or has developed a health problem severe enough to prevent curative treatment, including surgery.
Two large randomized studies have demonstrated that low-dose CT screening saves lives: the NLST (National Lung Screening Trial) conducted in the United States showed that low-dose CT screening reduced the risk of lung cancer death compared with chest radiography by %20 . The European (Netherlands-Belgium) study using a volume-based measurement protocol, NELSON study showed that, over 10 years of follow-up, the risk in men was reduced by approximately %24-26 , confirming the NLST finding.
In Türkiye, a national/population-based lung cancer screening invitation system run by the Ministry of Health, as there is for breast, cervical, and colorectal cancers, does not exist. Low-dose CT screening in high-risk people (those meeting the criteria above) is performed opportunistically in university and private hospitals at the physician's discretion, based on international criteria. If you are in a risk group, it is recommended that you discuss your eligibility for screening with your doctor.
How Is It Diagnosed?
When lung cancer is suspected, the diagnostic process generally proceeds through the following steps:
- Imaging: A chest X-ray is performed first, followed by a chest computed tomography (CT) scan for a more detailed assessment.
- Tissue diagnosis (biopsy): A sample of suspicious tissue must be obtained for a definitive diagnosis. This may be done using bronchoscopy, needle biopsy (CT-guided), endobronchial ultrasound (EBUS), or sometimes surgical methods.
- Staging imaging: PET-CT and, when necessary, a brain MRI are used to determine the extent of disease spread. For detailed information about PET-CT, see our article What Is PET-CT? Why Is It So Important in Cancer? for further details.
- Molecular (mutation) tests: Genetic alterations such as EGFR, ALK, ROS1, KRAS G12C, MET, RET, HER2, and BRAF, which directly affect treatment selection, are tested in biopsy tissue, particularly in patients diagnosed with NSCLC. PD-L1 immunohistochemistry testing is also used to predict the response to immunotherapy.
Lung cancer treatment has moved beyond the concept of "one-size-fits-all chemotherapy" and entered the era of personalized (targeted) therapy. Molecular testing in every patient diagnosed with advanced NSCLC is therefore critically important for enabling the use of targeted drugs when appropriate. Those wishing to understand generally how mutations cause cancer can read our article What Is a Mutation? How Does It Cause Cancer? and, specifically for EGFR testing, our article What Is an EGFR Mutation? How Is EGFR Testing Performed in Lung Cancer? provides further details.
Staging: The TNM System (9th Edition)
Lung cancer is staged using the internationally accepted TNM system : T (tumor size and spread to neighboring structures), N (spread to regional lymph nodes), and M (distant organ metastasis). The combination of these letters classifies the disease from Stage I to Stage IV.
Developed through the staging project of the IASLC (International Association for the Study of Lung Cancer), the 9th edition of TNM has been used worldwide as the new standard since January 1, 2025, replacing the previous 8th edition (2017). The subdivisions of the T category (size thresholds) have not changed; however, the N2 category has been divided according to single-station (N2a) / multistation (N2b) involvement, and the M1c category according to involvement of a single organ system (M1c1) / multiple organ systems (M1c2), with corresponding updates to some stage groupings.
A letter is placed before the TNM categories to indicate the information on which staging is based: c (clinical) — the pretreatment stage based on examination and imaging findings; p (pathological) — the most definitive stage, based on microscopic examination of surgically removed tissue; y (post-treatment) — restaging after chemotherapy or radiotherapy (ycTNM if surgery was not performed, ypTNM if it was). An E code indicating the type of information used for staging can also be added: E1 physical examination, E2 imaging, E3a cytology, E3b histology, E4 surgical specimen. For example, cT2aN2aM0 E3a indicates clinical staging in which lymph node involvement has been confirmed cytologically, while pT1cN0M0 E4 indicates pathological staging based on a surgical specimen.
T Category: Tumor Size and Local Spread
The T category is determined by the greatest diameter of the invasive (spreading) part of the tumor. Measurement is made from the pathological specimen or radiologically from the diameter of the solid component; multiplanar reconstruction measurements can also be used if they are larger than the axial measurement.
| T (Tumor) | Definition |
|---|---|
| T1a / T1b / T1c | Tumor ≤1 cm / 1-2 cm / 2-3 cm, without spread to surrounding tissues |
| T2a / T2b | Tumor 3-4 cm / 4-5 cm, or limited spread to the main bronchus/visceral pleura |
| T3 | Tumor 5-7 cm, or invasion of the chest wall/phrenic nerve/parietal pericardium, or an additional tumor nodule in the same lobe |
| T4 | Tumor >7 cm, or invasion of the diaphragm/mediastinum/heart/major vessels/trachea/esophagus, or an additional tumor nodule in a different lobe |
T1: Tumor ≤ 3 cm
The tumor is located within lung tissue or in a lobar/peripheral bronchus: T1mi — minimally invasive adenocarcinoma; T1a — ≤1 cm; T1b — 1-2 cm; T1c — 2-3 cm.
T2: Tumor 3-5 cm or specific anatomical characteristics
T2a — 3-4 cm; or invasion of the visceral pleura, involvement of the main bronchus (away from the carina), or atelectasis/obstructive pneumonia extending to the hilum. T2b — 4-5 cm (with or without T2a features).
T3: Tumor 5-7 cm or invasion of neighboring structures
Size 5-7 cm; or invasion of the parietal pleura/chest wall; or invasion of the pericardium, phrenic nerve, azygos vein, thoracic nerve roots/stellate ganglion; or in the same lobe a separate tumor nodule or nodules.
T4: Tumor >7 cm or invasion of critical structures
Larger than 7 cm; or invasion of the mediastinum, trachea, carina, esophagus, diaphragm, heart, major vessels, intrapericardial pulmonary vessels, vertebral body, spinal canal, cervical nerve roots, or brachial plexus; or in a different lobe on the same side a separate tumor nodule or nodules.
Ground-Glass and Part-Solid Lesions
Subsolid lesions with a "ground-glass" appearance on computed tomography form a group that generally shows a lepidic growth pattern and requires special staging rules. These lesions may be entirely ground-glass or may contain a solid component reflecting invasion (a part-solid lesion). For accurate staging, both the total lesion diameter and, if present, the greatest diameter of the solid component should be measured separately in the lung window on consecutive thin-section (≤1,5 mm) CT images.
Pure ground-glass lesions: If the total diameter is ≤30 mm, the lesion is classified according to its total size and is considered at most cTis (in situ). If the total diameter is >30 mm, the lesion is at least cT1a, even if its appearance is entirely ground-glass.
Part-solid lesions: Staging is based on the greatest diameter of the solid component , which is considered an indicator of the invasive part. For example, if the total diameter is ≤30 mm and the solid component is ≤5 mm, the lesion is cT1mi (minimally invasive); with the same ≤5 mm solid component but a total diameter >30 mm, the lesion is cT1a . If the solid component is 11-20 mm, it is cT1b; if it is 21-30 mm, it is cT1c.
How Is Disease Staged When There Are Multiple Lung Lesions?
The presence of multiple tumor sites in the lung is one of the most frequently confusing situations in staging; the rules are as follows:
- Separate synchronous primary tumors: Each tumor is assigned a separate TNM stage and evaluated independently of the others.
- Separate nodules of the same tumor: If they are in the same lobe, they are classified as T3; in a different lobe of the lung on the same side, as T4; in the opposite lung, as M1a . The patient is assigned a single N value and a single M value.
- Multiple ground-glass/lepidic lesions: Staging is based on the dominant lesion (the most advanced in terms of T); a single N and M are assigned, and the number of lesions is noted separately.
- Diffuse pneumonia-like adenocarcinoma: The same lymph node and metastasis rules apply (same lobe → T3; different lobe on the same side → T4; opposite lung → M1a).
N Category: Regional Lymph Nodes
| N (Lymph Node) | Definition |
|---|---|
| N0 | No regional lymph node involvement |
| N1 | Ipsilateral peribronchial / hilar lymph node involvement |
| N2a (new in the 9th ed.) | In ipsilateral mediastinal/subcarinal lymph nodes, a single station is involved |
| N2b (new in the 9th ed.) | In ipsilateral mediastinal/subcarinal lymph nodes, multiple stations are involved |
| N3 | Contralateral mediastinal/hilar or supraclavicular lymph node involvement on either side |
The IASLC Lymph Node Map
Regional lymph nodes include intrathoracic nodes and scalene and supraclavicular nodes. Involvement in less common locations, such as parasternal or axillary nodes, is considered metastatic rather than regional. The international standard IASLC lymph node map divides nodes into numbered stations:
- Lower cervical, supraclavicular, and suprasternal notch nodes
- Upper paratracheal nodes
- Prevascular (3A: nodes anterior to the vessels, not adjacent to the trachea) and prevertebral (3P: nodes behind the esophagus, not adjacent to the trachea)
- Lower paratracheal nodes
- Subaortic (aortopulmonary window) nodes
- Paraaortic (ascending aortic or phrenic) nodes
- Subcarinal nodes
- Paraesophageal nodes
- Nodes within the pulmonary ligament
- Hilar nodes (located outside the mediastinum)
Computed tomography alone is not reliable for lymph node staging, regardless of the size threshold chosen. PET-CT is substantially more reliable for determining N status and has a particularly high negative predictive value — meaning that the absence of uptake on PET-CT strongly supports the absence of involvement. However, sarcoidosis, tuberculosis, and other infections can produce false-positive results. Therefore, when the result would change the treatment plan, EBUS, mediastinoscopy, or biopsy is often needed for pathological confirmation of the findings.
N Stages in Right and Left Lung Tumors
For a right lung tumor: N1 — ipsilateral peribronchial and/or hilar nodes (10R-14R); N2 — ipsilateral mediastinal and/or midline nodes (2R, 3a/p, 4R, 7, 8R, 9R); N3 — contralateral mediastinal/hilar nodes and any supraclavicular node (1, 2L, 3aL, 4L, 5, 6, 8L, 9L, 10L-14L).
For a left lung tumor: N1 — ipsilateral peribronchial and/or hilar nodes (10L-14L); N2 — ipsilateral mediastinal and/or midline nodes (2L, 3a/p, 4L, 7, 8L, 9L); N3 — contralateral mediastinal/hilar nodes and any supraclavicular node (1, 2R, 3aR, 3pR, 4R, 8R, 9R, 10R-14R).
M Category: Distant Metastasis
| M (Metastasis) | Definition |
|---|---|
| M0 | No distant metastasis |
| M1a | A separate tumor nodule in the opposite lung, pleural/pericardial effusion |
| M1b | A single metastatic site in a single distant organ |
| M1c1 (new in the 9th ed.) | Multiple distant metastases, but within a single organ system |
| M1c2 (new in the 9th ed.) | Multiple distant metastases in multiple organ systems |
M1a — intrathoracic spread: Malignant pleural or pericardial fluid, pleural/pericardial nodules, or separate tumor nodules in the opposite lung.
M1b — a single metastatic site in a single organ system: For example, a single metastasis in the liver.
M1c1 — multiple metastases limited to a single organ system: For example, multiple metastatic sites confined to the bones.
M1c2 — metastases involving multiple organ systems: For example, both liver and brain metastases. The most common metastatic sites are the adrenal glands, brain, bones, liver, and nonregional lymph nodes.
Stage Grouping: The Combination of T, N, and M
The combination of these three categories (T, N, M) corresponds to a total of 11 substages, from IA1 to IVB, as shown in the table below. This is the complete stage grouping table updated according to the IASLC 9th edition:
| T / N | N0 | N1 | N2a (single station) | N2b (multiple stations) | N3 |
|---|---|---|---|---|---|
| T1a | IA1 | IIA | IIB | IIIA | IIIB |
| T1b | IA2 | IIA | IIB | IIIA | IIIB |
| T1c | IA3 | IIA | IIB | IIIA | IIIB |
| T2a | IB | IIB | IIIA | IIIB | IIIB |
| T2b | IIA | IIB | IIIA | IIIB | IIIB |
| T3 | IIB | IIIA | IIIA | IIIB | IIIC |
| T4 | IIIA | IIIA | IIIB | IIIB | IIIC |
| Metastasis Category | Stage (Independent of T and N) |
|---|---|
| M1a (contralateral lung nodule, pleural/pericardial effusion) | IVA |
| M1b (a single metastatic site in a single organ) | IVA |
| M1c1 (multiple metastases in a single organ system) | IVB |
| M1c2 (multiple metastases in multiple organ systems) | IVB |
In the 8th edition, N2 involvement (whether single-station or multistation) was considered a single category and generally corresponded to IIIA/IIIB. With the distinction between N2a (single station) and N2b (multiple stations) introduced in the 9th edition, for example, T1 N2b is now classified not as IIIA but as IIIB — because multistation mediastinal involvement has been shown to have a poorer prognosis than single-station involvement. Similarly, splitting the M1c category into M1c1/M1c2 reflects the possibility that extensive metastases limited to a single organ system (M1c1) may have a better prognosis than metastases involving multiple organ systems (M1c2) — although both remain classified within Stage IVB.
Stage groups are strongly associated with survival estimates: for example, in clinical Stage IA (cT1N0M0) disease, 5-year survival is approximately %82 whereas in Stage IVB (M1c), this rate falls to approximately %7. The refinements introduced in the 9th edition mainly aim to make prognostic grouping and corresponding treatment decisions more accurate by redistributing certain T-N combinations between IIA and IIIB.
The four main stages above are subdivided into numerous substages, from IA1 to IVB. Your doctor can determine the definitive stage only after imaging and, if necessary, surgical/pathological evaluation; this section provides only a general framework.
Treatment Methods
The treatment plan for lung cancer is personalized according to the cancer's histological type (NSCLC/SCLC), stage, the patient's overall health, and any genetic mutations detected in the tumor. Treatment tools include:
General Framework for the Treatment Approach by Stage
Each treatment method is discussed separately in the sections below; however, the framework determining which methods are used for which patients and in what order is as follows:
| Stage / Condition | Standard Treatment Approach |
|---|---|
| Stage I (T1-T2a N0) | Surgery (lobectomy + lymph node sampling); SBRT for patients unsuitable for surgery. In Stage IB, adjuvant chemotherapy is discussed if high-risk features are present. |
| Stage II (N1 involvement or T2b-T3 N0) | Surgery + adjuvant platinum-based chemotherapy; perioperative/neoadjuvant immunotherapy in eligible patients; adjuvant osimertinib if an EGFR mutation is present. |
| Stage IIIA — resectable | Surgery after neoadjuvant chemo-immunotherapy, followed by adjuvant immunotherapy (perioperative approach); or surgery + adjuvant treatment. A multidisciplinary tumor board decision is essential. |
| Stage IIIB-IIIC — inoperable | Concurrent chemoradiotherapy, followed by 1 year of durvalumab consolidation (PACIFIC); if an EGFR mutation is present, osimertinib instead of durvalumab (LAURA). |
| Stage IV — driver mutation present | The relevant targeted drug (osimertinib, lorlatinib, selpercatinib, etc.) as 1st-line treatment; immunotherapy is generally less effective in this group. |
| Stage IV — no driver mutation | Immunotherapy alone is an option if PD-L1 is ≥50%; otherwise, a combination of chemotherapy + immunotherapy. |
| Oligometastatic disease | In addition to systemic treatment, local treatment (SBRT or surgery) directed at a limited number of metastatic sites is considered. |
Surgery
In early-stage NSCLC (generally Stage I-II and selected Stage IIIA cases), surgical removal of the tumor and affected lung tissue is the foundation of curative treatment. The extent of the operation varies according to the tumor's size and location:
- Lobectomy: Removal of the entire lung lobe containing the tumor. It has been the standard operation for decades and remains the preferred method for most patients today.
- Segmentectomy / wedge resection: Removal of only part of the lobe. Long considered an "inadequate operation", this approach has been reassessed in recent years for small, peripherally located tumors (generally ≤2 cm, N0). The JCOG0802 and CALGB 140503 studies showed that, in these selected patients, segmentectomy/wedge resection provides oncological outcomes equivalent to lobectomy while preserving more lung function. This is an important step toward de-escalation in early-stage surgery.
- Pneumonectomy: Removal of an entire lung. It may be necessary for large, centrally located tumors, but it is avoided whenever possible because of its severe impact on respiratory function.
- Sleeve resection: A technique used for central tumors involving the main bronchus in which the affected bronchial segment is removed and the ends reconnected, allowing pneumonectomy to be avoided.
Surgery is always accompanied by systematic lymph node dissection or sampling — this is essential for accurate pathological staging and, consequently, the postoperative treatment decision. Today, most operations are performed using minimally invasive methods (VATS — video-assisted thoracoscopic surgery, or robotic surgery), resulting in less pain, a shorter hospital stay, and faster recovery compared with open surgery.
A patient's suitability for surgery depends not only on the cancer's stage but also on their respiratory reserve . Preoperative pulmonary function tests (particularly FEV1 and DLCO) are used to predict whether the remaining lung capacity after surgery will be sufficient; patients with borderline results also undergo exercise testing and cardiac assessment. This evaluation is critically important because most patients with lung cancer have coexisting lung diseases such as COPD related to their smoking history. SBRT is an important alternative for patients with early-stage disease whose respiratory reserve is insufficient.
Radiotherapy
Radiotherapy is used for three very different purposes in lung cancer, with a different method of delivery for each:
1. With Curative Intent: SBRT
Stereotactic body radiotherapy (SBRT)is a technique that focuses a very high dose on the tumor with millimeter precision in a small number of sessions (generally 3-8 fractions) in patients with early-stage disease (T1-T2 N0) who are unsuitable for surgery. In this group, it achieves a local control rate of around 85-90% , making it a genuine alternative to surgery. SBRT is also increasingly used as local treatment directed at a limited number of metastatic sites in oligometastatic disease.
2. Together with Chemotherapy: Concurrent Chemoradiotherapy
In inoperable Stage III disease, the standard approach is radiotherapy administered with platinum-based chemotherapy concurrently (generally 60-66 Gy over 6-7 weeks). Concurrent treatment is more effective than sequential treatment (chemotherapy first, then radiotherapy), but its side effects are also more severe. For patients who complete this treatment without disease progression, the current standard approach is to continue with durvalumab consolidation (PACIFIC) or, if an EGFR mutation is present, osimertinib (LAURA), discussed in detail below.
3. With Palliative (Symptom-Relieving) Intent
In advanced disease, radiotherapy is delivered using short regimens to relieve pain caused by bone metastases, control airway obstruction or bleeding (hemoptysis), relieve superior vena cava syndrome, or treat brain metastases. For brain metastases with a limited number of sites, the preferred approach instead of whole-brain radiotherapy is stereotactic radiosurgery ; this significantly reduces cognitive side effects.
Chemotherapy
Platinum-based chemotherapy (cisplatin or carboplatin, generally combined with a second agent) is an important component of treatment in both NSCLC and SCLC; it may be used alone, before/after surgery (neoadjuvant/adjuvant), or in combination with immunotherapy. The specific regimens used are discussed in detail by histology in the "Chemotherapy and Anti-Angiogenic Therapies" section below.
One of the most important changes in lung cancer treatment in recent years is that immunotherapy has begun to be used not only in advanced disease but also in surgically removable (resectable) early-to-intermediate-stage disease with curative intent:
- Neoadjuvant (before surgery): The combination of nivolumab + chemotherapy (CheckMate 816 study), administered before surgery in patients with resectable disease, has been shown to prolong survival, with confirmation in 2025 through 5-year follow-up data.
- Perioperative (both before and after surgery): Regimens using nivolumab, pembrolizumab, or durvalumab both before and after surgery (the CheckMate 77T, KEYNOTE-671, and AEGEAN studies, respectively) have become current standard treatment options for resectable Stage II-IIIA NSCLC.
- Adjuvant (after surgery) alone: Atezolizumab (PD-L1≥1%) or pembrolizumab (regardless of PD-L1 status) are approved adjuvant options for certain patients after surgery.
- In patients with an EGFR mutation: The use of adjuvant osimertinib for 3 years after surgery (ADAURA study) has become standard treatment, also supported by overall survival data published in 2023.
Targeted Therapies and Mutations
In advanced NSCLC, "targeted" drugs developed for specific genetic mutations detected in biopsy tissue can be much more effective than chemotherapy, generally with fewer side effects, in eligible patients. Below are the FDA-approved drugs for each mutation group, the studies supporting approval, and the specific effectiveness results obtained in these studies (PFS: progression-free survival, OS: overall survival, ORR: objective response rate, HR: hazard ratio).
EGFR Mutation (Exon 19 Deletion / L858R)
EGFR is the most frequently targeted mutation in lung adenocarcinomas. Osimertinib, a third-generation EGFR-TKI, is currently the standard 1st-line treatment: FLAURA showed that osimertinib increased PFS to 18,9 months (compared with 10,2 months in the comparator arm, HR 0,46) and also showed superiority in final overall survival, at 38,6 versus 31,8 months. The combination approved in 2024, osimertinib + chemotherapy (FLAURA2 study), further prolonged PFS compared with osimertinib alone, to 25,5 months (versus 16,7 months, HR 0,62). For postoperative (adjuvant) use, ADAURA showed that osimertinib reduced the risk of death by approximately 51% in patients with resected Stage IB-IIIA disease and increased 5-year overall survival from 78% to 88%. Another important development approved in 2024 concerns osimertinib used after chemoradiotherapy in inoperable (unresectable) Stage III disease: LAURA showed an increase in PFS from 5,6 to 39,1 months (HR 0,16) — one of the largest effectiveness differences seen to date with targeted therapies in lung cancer. Although older-generation EGFR-TKIs (gefitinib, erlotinib, afatinib, dacomitinib) are also approved, they are no longer preferred because osimertinib is superior in both effectiveness and control of brain metastases.
Amivantamab + lazertinib (approved in August 2024) was tested directly against osimertinib in MARIPOSA and showed superior PFS (23,7 versus 16,6 months, HR 0,70). At 3,5 years of follow-up, the overall survival rate also showed statistically significant superiority over osimertinib, at 56% versus 44% — making this the first regimen to show superior overall survival over osimertinib in 1st-line EGFR-mutated disease.
EGFR Exon 20 Insertion Mutation
This is a rarer subgroup that differs from conventional EGFR mutations and does not respond to standard EGFR-TKIs such as osimertinib. Amivantamab is approved alone in the 2nd line (CHRYSALIS study, ORR ~40%), while on March 1, 2024, approval was granted to amivantamab + chemotherapy , which is now the 1st-line standard: PAPILLON found PFS of 11,4 versus 6,7 months (HR 0,40) (on the same date, amivantamab's 2nd-line indication was also converted from accelerated to full approval).
Sunvozertinib, for advanced NSCLC with an EGFR exon 20 insertion that has progressed after platinum-based chemotherapy, on July 2, 2025, received accelerated FDA approval. It is important that it is the first oral targeted drug approved for this group: while amivantamab is an intravenously administered antibody, sunvozertinib can be taken as a daily tablet, offering a significant practical advantage in treatment access and quality of life.
ALK Rearrangement
Several generations of targeted drugs are available for ALK-positive patients. For the most current 1st-line standard, lorlatinib, the CROWN study reported that median PFS had not been reached, compared with crizotinib (9,3 months in the crizotinib arm, HR 0,28), and the response rate was 76% versus 58%. The previous-generation agents alectinib (ALEX study, PFS ~34,8 versus ~10,4 months, HR ~0,43; 5-year overall survival 62,5% versus 45,5%) and brigatinib (ALTA-1L study) remain 1st-line options supported by strong evidence. The older drugs crizotinib and ceritinib are also approved, but are no longer the first choice because newer-generation agents are superior, particularly in controlling brain metastases.
ROS1 Rearrangement
Crizotinib (ORR ~72%) and entrectinib (ORR ~67%, effective against brain metastases) have long been approved options. Two newer-generation drugs have been added in the past 2-3 years: Repotrectinib (approved in 2023, TRIDENT-1 study) showed a response rate of 79% in patients who had not received a TKI and 38% in patients who developed resistance after TKI treatment. Taletrectinib (approved on June 11, 2025, TRUST-I/II studies) showed response rates of 85-90% in patients who had not received a TKI and 52-62% in patients previously treated with a TKI.
The most important problem encountered in ROS1-positive disease is the development, after treatment with a first-generation TKI, of resistance mutations (particularly G2032R). Zidesamtinib, for patients whose disease has progressed after at least one ROS1-TKI treatment, on July 22, 2026, received FDA approval and, as of the date this article was prepared, is the newest approved drug in lung cancer. Its design against resistance mutations and strong penetration into the central nervous system provide an additional step in the treatment sequence for ROS1-positive patients.
MET Exon 14 Skipping Mutation and MET Overexpression
These are two different biomarkers. For the MET exon 14 skipping mutation, capmatinib (GEOMETRY mono-1 study, ORR 68% in previously untreated patients) and tepotinib (VISION study, ORR ~43-46%) are approved. For patients with MET protein overexpression (a different biomarker, not a mutation) and wild-type EGFR, the drug approved in May 2025, telisotuzumab vedotin (LUMINOSITY study, ORR 35%), can be used — this is the first MET-targeted antibody-drug conjugate.
RET Fusion
Selpercatinib (LIBRETTO-001 study: ORR 84% in previously untreated patients, ORR 61% in previously treated patients; PFS ~25 versus ~11 months in the randomized 1st-line LIBRETTO-431 study) and pralsetinib (ARROW study: ORR 78% in previously untreated patients, ORR 63% in previously treated patients) are two approved options for this group.
KRAS G12C Mutation
Sotorasib in the CodeBreaK 200 study was tested against docetaxel in the 2nd line and showed significantly superior PFS (5,6 versus 4,5 months, HR 0,66), but no significant difference in overall survival was found (10,6 versus 11,3 months). Adagrasib in KRYSTAL-12 similarly showed superior PFS (5,5 versus 3,8 months, HR 0,58; response rate 32% versus 9%). These two drugs are currently used in the second line; the limited clear benefit in overall survival means that patients and physicians need to make treatment decisions with this information in mind.
HER2 (ERBB2) Mutation
HER2 mutations occur in approximately 2-4% of lung adenocarcinomas and have become one of the fastest-developing fields, with successive approvals over the past three years. Trastuzumab deruxtecan (an antibody-drug conjugate), in DESTINY-Lung02 showed a response rate of 57,7% in the 2nd line and beyond and, on August 11, 2022, received the first HER2-targeted approval in lung cancer. On August 8, 2025, approval was granted to zongertinib , the first oral HER2-targeted small-molecule drug (Beamion LUNG-1 study: ORR 75% in patients who had not received an ADC, ORR 44% after ADC treatment).
Sevabertinib, for previously systemically treated patients with nonsquamous NSCLC harboring a HER2 (ERBB2) tyrosine kinase domain activating mutation, on November 19, 2025, received accelerated FDA approval. Subsequently, zongertinib's approval was expanded, on February 26, 2026, to include previously untreated (treatment-naive) patients with HER2 mutations — so patients with HER2 mutations now have an oral targeted option in the first line . This latest approval is the second approval granted under the FDA's "National Priority Voucher" pilot program, introduced to accelerate review.
BRAF V600E Mutation
Dabrafenib + trametinib (ORR ~64% in previously untreated patients) has long been approved. The combination approved in 2023, encorafenib + binimetinib (PHAROS study), offers a current alternative in this group, with a response rate of 75% in previously untreated patients.
NTRK Fusion and Other Antibody-Drug Conjugates
For patients with an NTRK fusion (approved regardless of cancer type, or "tumor-agnostic"), larotrectinib and entrectinib can be used (ORR ~57-75% in pooled analyses). In addition, in June 2025, for patients with EGFR-mutated disease that progressed after previous EGFR-TKI + chemotherapy, datopotamab deruxtecan (TROPION-Lung studies, ORR 45%) was approved.
Antibody-drug conjugates are a new generation of drugs that link an antibody recognizing a target specific to the cancer cell with a powerful chemotherapy agent. The antibody aims to increase effectiveness and reduce harm to healthy tissues by carrying the drug directly to the cancer cell. Trastuzumab deruxtecan, datopotamab deruxtecan, and telisotuzumab vedotin are drugs in this class approved for lung cancer.
| Mutation | Approved Drug(s) | Pivotal Study | Key Effectiveness Data |
|---|---|---|---|
| EGFR (exon19del/L858R), 1st line | Osimertinib | FLAURA | PFS 18,9 vs 10,2 months, HR 0,46 |
| EGFR, 1st-line combination | Osimertinib+chemotherapy | FLAURA2 (2024) | PFS 25,5 vs 16,7 months, HR 0,62 |
| EGFR, adjuvant | Osimertinib | ADAURA | 5-year OS 88% vs 78% |
| EGFR, Stage III post-CRT | Osimertinib | LAURA (2024) | PFS 39,1 vs 5,6 months, HR 0,16 |
| EGFR, chemotherapy-free 1st line | Amivantamab+lazertinib | MARIPOSA (2024) | PFS 23,7 vs 16,6 months; superior OS |
| EGFR exon20ins, 1st line | Amivantamab+chemotherapy | PAPILLON (2024) | PFS 11,4 vs 6,7 months, HR 0,40 |
| ALK, 1st line | Lorlatinib | CROWN | PFS HR 0,28; ORR 76% vs 58% |
| ROS1 | Repotrectinib (2023), taletrectinib (2025) | TRIDENT-1, TRUST-I/II | TKI-naive ORR 79-90% |
| MET exon14 skipping | Capmatinib, tepotinib | GEOMETRY mono-1, VISION | ORR 43-68% |
| MET overexpression | Telisotuzumab vedotin (2025) | LUMINOSITY | ORR 35% |
| RET fusion | Selpercatinib, pralsetinib | LIBRETTO-001, ARROW | ORR 61-84% |
| KRAS G12C | Sotorasib, adagrasib | CodeBreaK 200, KRYSTAL-12 | PFS HR 0,58-0,66; limited OS benefit |
| HER2 mutation | Trastuzumab deruxtecan, zongertinib (2025) | DESTINY-Lung02, Beamion LUNG-1 | ORR 58-75% |
| BRAF V600E | Dabrafenib+trametinib, encorafenib+binimetinib (2023) | PHAROS | ORR 64-75% |
| NTRK fusion | Larotrectinib, entrectinib | Pooled basket trials | ORR 57-75% |
| EGFR-mutant, 2nd-line ADC | Datopotamab deruxtecan (2025) | TROPION-Lung | ORR 45% |
Mobosertinib (mobocertinib, Exkivity), despite receiving accelerated approval for EGFR exon 20 insertion on September 15, 2021, was subject to withdrawal after the confirmatory phase 3 study (EXCLAIM-2) failed to show the expected benefit: on October 2, 2023, the manufacturer announced that it would voluntarily withdraw the drug, and the official revocation of its authorization on July 15, 2024, took effect. It is no longer an active treatment option — current options for this group are amivantamab and sunvozertinib. This example also illustrates how a drug introduced through accelerated approval can be withdrawn when its confirmatory study fails, demonstrating the system's ability to correct itself.
Immunotherapy
Immunotherapy (particularly PD-1/PD-L1 checkpoint inhibitors) has revolutionized lung cancer treatment over the past 10 years by enabling the immune system to recognize and destroy cancer cells. The main agents currently used are: pembrolizumab, nivolumab, atezolizumab, durvalumab, ipilimumab, and cemiplimab. Below are the approved uses of each agent, the pivotal study supporting them, and the specific effectiveness results achieved. For the general mechanism of immunotherapy, see our article What Is Immunotherapy? Mobilizing the Immune System Against Cancer and, for a comparison of immunotherapy and chemotherapy side effects in lung cancer, this article provides further information.
Pembrolizumab
As 1st-line monotherapy with PD-L1≥50% (KEYNOTE-024), at 5 years of follow-up, overall survival was 26,3 months versus 13,4 months in the chemotherapy arm (HR 0,62), and the 5-year survival rate was 31,9% versus 16,3%. In 1st-line use combined with chemotherapy regardless of PD-L1 level, for nonsquamous histology (KEYNOTE-189), overall survival was 22,0 versus 10,6 months; for squamous histology (KEYNOTE-407), it was reported as 17,1 versus 11,6 months. After surgery (adjuvant, KEYNOTE-091), it prolonged disease-free survival to 53,6 versus 42,0 months; in perioperative use (KEYNOTE-671), it significantly prolonged event-free survival (EFS) and showed 36-month overall survival of 71% versus 64%.
Nivolumab
In neoadjuvant use (CheckMate 816), 5-year follow-up data (2025) showed a 28% reduction in the overall survival hazard (HR 0,72) and a superior 5-year survival rate of 65% versus 55%; the pathological complete response rate also differed strikingly, at 24% versus only 2,2%. In perioperative use (CheckMate 77T), the event-free survival hazard decreased by 42% (HR 0,58). In 2nd-line use for advanced disease (CheckMate 017/057), at 5 years of follow-up, overall survival was 11,1 versus 8,1 months, and the 5-year survival rate was 13,4% versus only 2,6%.
Atezolizumab
After surgery (adjuvant, IMpower010), the disease-free survival hazard decreased by 57% in the PD-L1≥50% subgroup (HR 0,43) — however, superior overall survival in the overall population was not statistically significant; this nuance is important when informing patients. As 1st-line monotherapy with high PD-L1 expression (IMpower110), overall survival was 20,2 versus 13,1 months (HR 0,59). In a 4-drug combination with bevacizumab, carboplatin, and paclitaxel (IMpower150, the "ABCP" regimen), overall survival was reported as 19,2 versus 14,7 months.
Durvalumab
Its use as consolidation treatment after chemoradiotherapy in inoperable Stage III disease (PACIFIC study) produced one of the most important results of the past 10 years in lung cancer treatment: overall survival of 47,5 versus 29,1 months (HR 0,72), and a 5-year survival rate of 42,9% versus 33,4%. In perioperative use (AEGEAN study), the event-free survival hazard also decreased significantly (HR ~0,68).
Other Agents
Ipilimumab is used in the 1st line in a three-part combination with nivolumab and short-course chemotherapy (2 cycles) (CheckMate 9LA study: overall survival 15,6 versus 10,9 months, HR 0,66). Cemiplimab is approved as 1st-line monotherapy in patients with PD-L1≥50% (EMPOWER-Lung 1 study: overall survival 26,1 versus 13,3 months, HR 0,57).
| Use | Agent(s) | Pivotal Study | Key Result |
|---|---|---|---|
| Neoadjuvant (resectable, +chemotherapy) | Nivolumab | CheckMate 816 | 5-year OS 65% vs 55% |
| Perioperative | Nivolumab, pembrolizumab, durvalumab | CheckMate 77T, KEYNOTE-671, AEGEAN | Superior EFS/OS in all studies |
| Adjuvant | Atezolizumab (PD-L1≥1%), pembrolizumab | IMpower010, KEYNOTE-091 | DFS HR 0,66-0,76; OS not yet statistically established |
| Consolidation (Stage III, post-CRT) | Durvalumab | PACIFIC | OS 47,5 vs 29,1 months, HR 0,72 |
| 1st line, PD-L1≥50% monotherapy | Pembrolizumab, atezolizumab, cemiplimab | KEYNOTE-024, IMpower110, EMPOWER-Lung 1 | OS HR 0,57-0,62 |
| 1st line +chemotherapy (regardless of PD-L1) | Pembrolizumab, atezolizumab | KEYNOTE-189/407, IMpower130/132/150 | OS HR 0,60-0,81 (IMpower132 not significant) |
| 1st line, dual immunotherapy+chemotherapy | Nivolumab+ipilimumab+chemotherapy | CheckMate 9LA | OS 15,6 vs 10,9 months, HR 0,66 |
Switching to a second immunotherapy after disease progression is not supported by current guidelines or reimbursement rules in Türkiye because its effectiveness is generally low. In addition, as illustrated by IMpower010 and IMpower132, some regimens showing significant benefit in disease-free survival/progression-free survival have not yet (or have never) reached statistical significance in overall survival; this distinction is important for appropriately managing treatment expectations.
Chemotherapy and Anti-Angiogenic Therapies
Even in the era of targeted therapy and immunotherapy, platinum-based chemotherapy remains a cornerstone of lung cancer treatment — used alone, combined with immunotherapy, or (rarely) with an antiangiogenic agent.
Standard Chemotherapy Regimens
- Nonsquamous histology (adenocarcinoma, etc.): Platinum (cisplatin or carboplatin) + pemetrexed is the standard combination; pemetrexed is not used in squamous cell cancer because it has been found ineffective in this histology.
- Squamous cell histology: Platinum + paclitaxel (or nab-paclitaxel) is the standard combination.
- Alternative doublets: Platinum + gemcitabine (particularly in squamous histology) and platinum + vinorelbine (preferred particularly for older/frail patients).
- Second line: Docetaxel can be used alone or combined with ramucirumab.
Anti-Angiogenic Agents
Bevacizumab (a VEGF inhibitor), when added to carboplatin+paclitaxel in nonsquamous histology (ECOG 4599 study), prolonged overall survival to 12,3 versus 10,3 months (HR 0,70); it is also a component of the IMpower150 regimen (atezolizumab+bevacizumab+chemotherapy). Ramucirumab (a VEGFR2 inhibitor), when added to docetaxel in the 2nd line (REVEL study), prolonged overall survival to 10,5 versus 9,1 months (HR 0,86).
Treatment of Small Cell Lung Cancer (SCLC)
SCLC is a disease that grows much faster than NSCLC and has a strong tendency to spread even at an early stage; the treatment approach is therefore fundamentally different.
Limited-Stage SCLC
The standard treatment is concurrent chemoradiotherapy: platinum (generally cisplatin) + etoposide chemotherapy is administered together with radiotherapy to the chest. The classic Turrisi study showed that radiotherapy delivered twice daily (hyperfractionated) increased 5-year survival from 16% to 26% compared with a single daily dose. In patients who achieve a complete response, to prevent microscopic spread to the brain, prophylactic cranial irradiation (PCI) is administered; this approach has been shown to increase 3-year survival from 15,3% to 20,7% and reduce the risk of brain metastases by approximately half.
ADRIATIC showed that durvalumab consolidation in patients with limited-stage disease without progression after chemoradiotherapy prolonged overall survival to 55,9 versus 33,4 months (HR 0,73). Based on this result, on December 4, 2024, durvalumab consolidation received FDA approval, becoming the first major treatment advance in limited-stage SCLC in years — notably, this demonstrates that the concept of "immunotherapy consolidation after chemoradiotherapy", proven in NSCLC by the PACIFIC study, also worked years later in small cell disease.
Extensive-Stage SCLC — 1st Line
The standard 1st-line treatment adds an immunotherapy agent to platinum+etoposide chemotherapy: atezolizumab (IMpower133 study: overall survival 12,3 versus 10,3 months, HR 0,70; March 18, 2019 approval) or durvalumab (CASPIAN study, updated 3-year data: 3-year survival rate 17,6% versus only 5,8% — approximately 3 times as many patients are alive at 3 years).
Atezolizumab's 2019 approval is frequently described as "the first immunotherapy approval in SCLC"; in fact, nivolumab received accelerated approval for third-line SCLC on August 16, 2018 (this indication was subsequently withdrawn). Atezolizumab's true historical importance is that it was the first immunotherapy approved in the first line and was, in extensive-stage SCLC, the first new first-line regimen in approximately 20 years .
IMforte showed that, after 4 cycles of induction treatment, the lurbinectedin + atezolizumab maintenance combination prolonged overall survival to 13,2 versus 10,6 months compared with atezolizumab maintenance alone (HR 0,73). Based on these data, the combination on October 2, 2025, received FDA approval — an important change indicating that the post-induction maintenance period is now also an active treatment window in extensive-stage SCLC.
Second Line and Beyond
Long-used topotecan was approved because it provides survival similar to the conventional CAV regimen but superior symptom control. Lurbinectedin monotherapy received accelerated approval in 2020 (ORR 35%); however, its single-agent indication is reportedly undergoing withdrawal because the confirmatory phase 3 study (LAGOON) did not meet its primary overall survival endpoint — its combined maintenance use with atezolizumab (the IMforte approval above) remains valid. Consequently, current 2nd-line treatment is shifting toward tarlatamab.
Tarlatamab is an entirely new class of DLL3-targeted drug that directs immune cells (T cells) directly to cancer cells (a bispecific T-cell engager / BiTE). In previously treated extensive-stage SCLC, the single-arm DeLLphi-301 study showed a response rate of 40% and overall survival of 14,3 months. It received, on May 16, 2024, accelerated approval. The confirmatory phase 3 study, DeLLphi-304, tested tarlatamab against chemotherapy and showed significantly superior overall survival (13,6 versus 8,3 months, HR 0,60); based on these data, on November 19, 2025, the approval was converted to full approval. Tarlatamab's most characteristic side effect is cytokine release syndrome, which is common with the first doses and generally mild to moderate (see the Side Effects section).
Global Approval and Evidence Timeline
Lung cancer has been the fastest-changing field in oncology over the past twenty years: a process that began with a single targeted drug in 2003 has now become a treatment map covering dozens of different biomarkers and drug classes. The timeline below summarizes the milestones of this transformation alongside their FDA approval dates.
It received accelerated approval in third-line NSCLC — the beginning of the "smart drug" era in lung cancer. However, when the confirmatory ISEL study failed to show benefit in the overall population, its use was severely restricted on June 17, 2005; its authorization was officially revoked on April 25, 2012.
It was approved as the second EGFR-TKI and remained the representative of this class in use during the years when gefitinib was restricted.
This approval, coming only four years after ALK rearrangement was identified, firmly established the understanding that lung cancer is not a single disease but a group of molecular subtypes.
Based on CheckMate 017 data, it was approved for squamous NSCLC that progressed after platinum treatment — launching the checkpoint inhibitor era in lung cancer. Pembrolizumab followed on October 2, 2015, and nivolumab's nonsquamous indication on October 9, 2015.
With a new authorization application, gefitinib was reapproved only for patients with an EGFR mutation as 1st-line treatment — the most striking example of how biomarker selection can change a drug's fate.
It received accelerated approval for patients with a T790M mutation who had developed resistance to previous-generation EGFR-TKIs (converted to full approval on March 30, 2017).
Based on KEYNOTE-024 data, it was approved in patients with PD-L1 ≥50%, replacing chemotherapy, alone as 1st-line treatment — the first time a chemotherapy-free first line became possible in advanced lung cancer.
Durvalumab consolidation after chemoradiotherapy was approved for inoperable Stage III disease; by increasing 5-year survival from 33,4% to 42,9%, it permanently changed the standard treatment for this stage.
It became standard 1st-line treatment in patients with EGFR mutations; its superior control of brain metastases largely surpassed previous-generation drugs.
Based on IMpower133 data, it became the first immunotherapy approved in the first line for extensive-stage SCLC — the first new first-line regimen for this disease in approximately two decades.
Postoperative osimertinib was approved for resected EGFR-mutated disease; it increased 5-year overall survival from 78% to 88% — the first major step in moving targeted therapy from advanced to early-stage disease.
It received full 1st-line approval in ALK-positive disease; with a PFS HR of 0,28 compared with crizotinib, it produced the strongest result in this class.
The first drug developed against the KRAS protein, considered "undruggable" for forty years, received accelerated approval in KRAS G12C-mutated NSCLC — the moment when one of oncology's greatest longstanding unsolved problems was overcome for the first time.
Based on IMpower010 data, postoperative immunotherapy was approved in patients with resected disease and PD-L1 ≥1% (pembrolizumab followed on January 26, 2023).
Preoperative chemo-immunotherapy was approved in resectable NSCLC; with a striking difference in pathological complete response rates of 24% versus 2,2%, it began the redesign of early-stage treatment.
Based on DESTINY-Lung02 data, it received accelerated approval in HER2-mutated NSCLC with a response rate of 57,7% — the first success of antibody-drug conjugates in lung cancer.
The first perioperative immunotherapy regimen used both before and after surgery was approved; AEGEAN (durvalumab, August 15, 2024) and CheckMate 77T (nivolumab, October 3, 2024) followed.
It received accelerated approval as a DLL3-targeted bispecific T-cell engager; with the results of the confirmatory DeLLphi-304 study, on November 19, 2025, it was converted to full approval (overall survival 13,6 versus 8,3 months).
Osimertinib after chemoradiotherapy was approved for inoperable Stage III EGFR-mutated disease; PFS increased from 5,6 to 39,1 months (HR 0,16) — one of the largest effectiveness differences seen in lung cancer.
It was approved as consolidation after chemoradiotherapy; it prolonged overall survival from 33,4 to 55,9 months.
The new staging system developed by the IASLC became the standard worldwide; the N2a/N2b and M1c1/M1c2 distinctions refined prognostic estimates.
Telisotuzumab vedotin (MET overexpression, May 14), taletrectinib (ROS1, June 11), datopotamab deruxtecan (EGFR-mutated, June 23), sunvozertinib (EGFR exon20ins, July 2), zongertinib (HER2, August 8), lurbinectedin+atezolizumab maintenance (October 2), and sevabertinib (HER2, November 19) — seven new approvals in a single year.
Approval was granted for treatment-naive use in patients with HER2 mutations; it was the second approval accelerated under the FDA's "National Priority Voucher" pilot program.
It was approved for patients whose disease progressed after previous ROS1-TKI treatment — the most current FDA approval in lung cancer as of the date this guide was prepared.
Prognosis, Survival, and Prognostic Factors
Survival in lung cancer varies greatly according to the stage at diagnosis. The current 5-year overall survival rate reported in the American Cancer Society's "Cancer Statistics, 2026" report, published on January 13, 2026, and based on a cohort of patients diagnosed between 2015-2021, is approximately %28— in the cohort diagnosed in the mid 1990s, the comparison point in the same report, this rate was only 15%. Approximate survival rates by stage are:
| Stage / Extent of Spread | Approximate 5-Year Survival |
|---|---|
| Localized (confined to the lung) | ~%60-65 |
| Regional (spread to nearby lymph nodes) | %37 |
| Distant (metastatic) | %10 |
Unfortunately, more than half of patients with lung cancer are already at the distant (metastatic) stage when diagnosed — highlighting the importance of early detection and screening programs for high-risk people (low-dose CT screening). Survival rates are continuously improving with rapid treatment developments (targeted therapies, immunotherapy); this table reflects the general statistical trend, while individual prognosis depends on many factors.
Prognostic Factors Other Than Stage
Although stage is the most important factor determining prognosis, it is not sufficient on its own. Other prognostic factors well defined in the literature are:
- Overall performance status (ECOG): In patients with advanced disease treated with immunotherapy, median overall survival is 13,4 months in those with ECOG performance status 0-1, but falls to only 3,3 months in those with ECOG ≥2 — one of the largest effect sizes from a single factor.
- Weight loss at diagnosis: Unintentional weight loss of ≥5% within two months increases the risk of death by approximately 65% (HR 1,65).
- Site of metastasis: According to SEER data, liver metastases (median survival 5,5 months) and metastases in multiple organs (5,8 months) indicate a poorer prognosis than bone (7,4 months) or brain metastases (8,2 months).
- Number of metastases (oligometastatic disease): In "oligometastatic" disease with a single or small number of metastatic sites (generally ≤3-5), the overall survival hazard is approximately 35% lower than in widespread (polymetastatic) disease (HR 0,65) — local treatments directed at metastases (such as SBRT) may sometimes be considered in this patient group.
- PD-L1 expression: In patients receiving immunotherapy, high PD-L1 is a strong positive predictive factor (HR 0,62 in KEYNOTE-024); however, in patients with early-stage disease who underwent surgery but did not receive immunotherapy, PD-L1 positivity was instead found to be an unfavorable prognostic sign — demonstrating that PD-L1's "predictive" role (predicting treatment response) should not be confused with its "prognostic" role (predicting the natural course of disease).
- KRAS mutation: In KRAS-mutant patients, the overall survival hazard is approximately 56% higher than in those with wild-type disease (HR 1,56).
- Smoking status: Median survival in patients who have never smoked (79,2 months) is significantly longer than in former/current smokers (46,8 months).
- Histology: In early-stage disease, squamous cell carcinoma generally has a poorer course than adenocarcinoma.
- Age: On its own (independently of performance status and comorbidities), it is not a strong prognostic factor; the effect of age is largely indirect, through comorbidities and performance status.
Treatment Side Effects and Their Management
The side effect profile of lung cancer treatments varies greatly according to the drug class used; each class has its own "characteristic" side effects:
EGFR Inhibitors (Osimertinib and Similar Drugs)
The most common side effects are paronychia (inflammation around the nails) and an acneiform rash; preventive treatment with antibiotics such as doxycycline and nail care are recommended. Diarrhea is common (40-50%) and is managed with loperamide. Specifically with osimertinib, QTc prolongation may occur; regular ECG monitoring and attention to electrolyte balance are therefore needed. The most serious but rare (2-4%) side effect is interstitial lung disease/pneumonitis; if suspected, the drug must be stopped immediately and steroid treatment is required.
ALK Inhibitors (Particularly Lorlatinib)
Specifically with lorlatinib, elevated cholesterol and triglycerides are very common (70-80%) and are generally managed proactively with a statin/fibrate. Mood changes, cognitive slowing, and speech disturbances are central nervous system effects (20-30%) specific to lorlatinib and are managed by dose reduction/interruption; it is important to inform patients and their loved ones about these effects in advance. Edema and weight gain are also common.
Immunotherapy Drugs (Checkpoint Inhibitors)
"Immune-related adverse events" (irAEs) caused by excessive activation of the immune system can affect almost any organ: pneumonitis (particularly important in patients with lung cancer; it can be mistaken for disease progression or infection), colitis (diarrhea, abdominal pain), hepatitis (elevated liver enzymes), endocrine disorders (thyroiditis, hypophysitis, adrenal insufficiency — these latter conditions are generally permanent and require lifelong hormone replacement), and skin reactions. The general management principle is based on grading: for mild (Grade 1) side effects, treatment is continued with close monitoring; for moderate (Grade 2) side effects, the drug is withheld and corticosteroids started; for severe (Grade 3-4) side effects, the drug is permanently discontinued, high-dose corticosteroids administered, and, if there is no response, additional immunosuppressive treatment is used (for example, infliximab for colitis).
KRAS G12C Inhibitors (Sotorasib, Adagrasib)
With both drugs, liver toxicity (requiring regular liver function monitoring) may occur; this is more pronounced with sotorasib. Specifically with adagrasib, marked nausea, vomiting, and diarrhea, along with QTc prolongation , occur more frequently and require electrolyte monitoring.
Antibody-Drug Conjugates (Trastuzumab Deruxtecan, etc.)
The most important side effect of this drug class, highlighted by the FDA with a "boxed warning", is interstitial lung disease/pneumonitis(occurring in approximately 10-15%); regular imaging follow-up and immediate evaluation of new respiratory symptoms are therefore required. Nausea/vomiting (managed with preventive antiemetics) and bone marrow suppression (regular blood count monitoring) may also occur.
Tarlatamab (T-Cell Engager Drug)
The most characteristic side effect, occurring in approximately half of patients and generally with the first 1-2 doses, is cytokine release syndrome(fever, low blood pressure, low oxygen levels); the first doses are therefore administered in hospital, and treatment with tocilizumab (an IL-6 receptor blocker) is used when necessary. Less frequent (around 8%) neurotoxicity (ICANS) can cause findings ranging from confusion to encephalopathy and is managed with corticosteroids.
Standard Chemotherapy (Platinum Agents, Pemetrexed, Taxanes)
Cisplatin characteristically causes kidney toxicity (intensive hydration and magnesium supplementation are required); carboplatin primarily causes bone marrow suppression (particularly low platelet counts). Pemetrexed can have its serious side effects substantially reduced through supplementation started before the first dose with vitamin B12 and folic acid . Taxanes (paclitaxel, docetaxel) characteristically cause cumulative and sometimes permanent peripheral neuropathy; paclitaxel also requires steroid/antihistamine premedication because of the risk of hypersensitivity reactions.
For more information on side effect management, see our articles What Are the Side Effects of Immunotherapy Drugs, and How Are They Treated? and How Can Chemotherapy Side Effects Be Reduced? for further details.
Diagnosis, Authorization, and Reimbursement in Türkiye
In Türkiye, lung cancer diagnosis and treatment are carried out in oncology centers at university hospitals and training and research hospitals in line with international guidelines. For drugs to be used in Türkiye, authorization from TİTCK (the Turkish Medicines and Medical Devices Agency) is first required; for coverage by SGK (the Social Security Institution), a separate reimbursement decision under SUT (the Healthcare Implementation Communiqué) is also necessary.
The SUT amendment dated July 10, 2025 substantially expanded reimbursement coverage for checkpoint inhibitor (immunotherapy) drugs in lung cancer. Under the current provisions, SGK covers pembrolizumab, nivolumab, atezolizumab, and durvalumab under certain criteria (such as PD-L1 level, stage, and absence of mutations). Ipilimumab is reimbursed only in a three-part combination with nivolumab and chemotherapy, with a limited number of doses (a maximum of 4). As a common restriction, switching to a second immunotherapy after disease progression on a checkpoint inhibitor is not covered by SGK.
Osimertinib is authorized in Türkiye and covered by SGK; however, the use clearly confirmed by our sources is limited to patients positive for the EGFR T790M mutation who have progressed after previous EGFR-targeted treatment (second line). Whether the current global standard, 1st-line use (in patients positive for exon 19 deletion/L858R), is covered by SGK could not be clearly confirmed from our sources; for current and definitive information, we recommend consulting the oncology specialist managing your treatment. Sotorasib and trastuzumab deruxtecan (Enhertu) are authorized in Türkiye but, according to our sources, are not covered by SGK. Adagrasib and serplulimab have no record of authorization in Türkiye that we could find.
Drug authorization and reimbursement status can change frequently with SUT updates. The information in this section is a general summary compiled as of the article's update date (August 2026); always confirm definitive and current information about your individual treatment and reimbursement situation with your treating physician and SGK's current SUT text.
Frequently Asked Questions
- Can lung cancer be cured if detected at an early stage?
- Yes. Patients diagnosed at an early stage (Stage I-II) who can be treated surgically have a substantially higher long-term cure rate than those with advanced disease. Early diagnosis is therefore very important for people in risk groups.
- Can someone who has never smoked develop lung cancer?
- Yes, it is possible. Factors such as radon gas, air pollution, genetic predisposition, and certain occupational exposures can cause lung cancer even in people who have never smoked; adenocarcinoma histology and certain targetable mutations (particularly EGFR) are detected more frequently in cancers in this group.
- Is mutation testing performed for every patient?
- Guidelines recommend mutation testing in patients diagnosed with advanced (metastatic) NSCLC because it directly affects treatment selection. Testing is also becoming increasingly common in patients with operable early-stage disease because it can affect the adjuvant treatment decision.
- Can immunotherapy be given to everyone?
- No. The effectiveness of immunotherapy depends on factors such as PD-L1 expression level, the presence of certain mutations in the tumor, such as EGFR/ALK (effectiveness is generally lower with these mutations), and disease stage. Your doctor evaluates eligibility.
- Why might the stage in my old report differ from the new stage?
- Because the TNM 9th edition took effect on January 1, 2025, the same tumor can have different stage names under the old (8th edition) and new systems. The most common situation is a shift in disease involving multiple mediastinal lymph node stations (N2b) from Stage IIIA to IIIB. This does not mean the disease has worsened — it only indicates that the classification has become more detailed. It is therefore important for reports to specify which edition was used.
- Will my entire lung be removed during surgery?
- Not in most patients. The standard operation removes only the lobe containing the tumor (lobectomy); in small, peripherally located tumors, an even more limited operation (segmentectomy or wedge resection) may be sufficient — the JCOG0802 and CALGB 140503 studies showed outcomes equivalent to lobectomy in selected patients with this approach. Removal of the entire lung (pneumonectomy) may be necessary only for large, centrally located tumors and is avoided whenever possible.
- Sung H, et al. "Global cancer statistics 2024." CA: A Cancer Journal for Clinicians, 2026. DOI: 10.3322/caac.70090
- IARC Global Cancer Observatory (GLOBOCAN 2024) — Türkiye Country Fact Sheet. gco.iarc.who.int
- Siegel RL, et al. "Cancer Statistics, 2026." CA: A Cancer Journal for Clinicians, 2026.
- American Cancer Society. "Key Statistics for Lung Cancer" and "Survival Rates for Lung Cancer" (January 2026 update). cancer.org
- US Preventive Services Task Force. "Lung Cancer: Screening" (current 2021 guideline). uspreventiveservicestaskforce.org
- National Lung Screening Trial Research Team. NEJM 2011;365:395-409 (NLST). de Koning HJ, et al. NEJM 2020;382:503-513 (NELSON).
- IASLC Staging Project. "The New 9th Edition TNM Classification for Lung Cancer is Now in Use" (effective: January 1, 2025).
- Soria JC, et al. "Osimertinib in Untreated EGFR-Mutated Advanced NSCLC" (FLAURA). NEJM 2018. Planchard D, et al. (FLAURA2), NEJM 2023-2024.
- Wu YL, et al. "Osimertinib in Resected EGFR-Mutated NSCLC" (ADAURA), overall survival data. NEJM, 2023.
- Lu S, et al. "Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC" (LAURA). NEJM 2024.
- Cho BC, et al. "Amivantamab plus Lazertinib in NSCLC" (MARIPOSA). NEJM 2024. Zhou C, et al. (PAPILLON), NEJM 2024.
- Solomon BJ, et al. "Lorlatinib in ALK-Positive NSCLC" (CROWN). NEJM 2020, updates 2024-2025.
- Skoulidis F, et al. (CodeBreaK 200); Jänne PA, Yu HA, et al. (KRYSTAL-12) — phase 3 data for KRAS G12C inhibitors.
- Forde PM, et al. "Neoadjuvant Nivolumab plus Chemotherapy" (CheckMate 816), 5-year follow-up data, ASCO/WCLC 2025.
- Antonia SJ, et al. "Durvalumab after Chemoradiotherapy in Stage III NSCLC" (PACIFIC), 5-year update. NEJM 2017, 2022.
- Reck M, et al. (KEYNOTE-024, 5-year follow-up); Gandhi L, et al. (KEYNOTE-189); Paz-Ares L, et al. (KEYNOTE-407).
- Cheng Y, et al. "Durvalumab after Chemoradiotherapy in Limited-Stage SCLC" (ADRIATIC). NEJM 2024. Paz-Ares L, et al. (CASPIAN, 3-year update).
- Ahn MJ, et al. "Tarlatamab for Small-Cell Lung Cancer" (DeLLphi-301). NEJM 2023; DeLLphi-304 phase 3 data, ASCO 2025.
- Detterbeck FC, Rami-Porta R, et al. IASLC Staging Project: 9th edition recommendations for T, N, and M categories. J Thorac Oncol / CHEST, 2024.
- Travis WD, et al. Staging and solid component measurement rules for subsolid (ground-glass/part-solid) lesions; IASLC lymph node map.
- Saji H, et al. JCOG0802 (segmentectomy vs lobectomy). Lancet 2022. Altorki N, et al. CALGB 140503. NEJM 2023.
- FDA approval announcements (2003-2026): gefitinib (May 5, 2003, reapproval July 13, 2015), erlotinib (November 18, 2004), crizotinib (August 26, 2011), nivolumab (March 4, 2015), pembrolizumab (October 2, 2015; KEYNOTE-024, October 24, 2016), osimertinib (November 13, 2015; FLAURA April 18, 2018; ADAURA December 18, 2020; FLAURA2 February 16, 2024; LAURA September 25, 2024), durvalumab (PACIFIC February 16, 2018; AEGEAN August 15, 2024; ADRIATIC December 4, 2024), atezolizumab (IMpower133 March 18, 2019; IMpower010 October 15, 2021), lorlatinib (March 3, 2021), sotorasib (May 28, 2021), neoadjuvant nivolumab (March 4, 2022), trastuzumab deruxtecan (August 11, 2022), adagrasib (December 12, 2022), adjuvant pembrolizumab (January 26, 2023), perioperative pembrolizumab (October 16, 2023), repotrectinib (November 15, 2023), amivantamab+chemotherapy (March 1, 2024), tarlatamab (May 16, 2024; full approval November 19, 2025), amivantamab+lazertinib (August 19, 2024), perioperative nivolumab (October 3, 2024), telisotuzumab vedotin (May 14, 2025), taletrectinib (June 11, 2025), datopotamab deruxtecan (June 23, 2025), sunvozertinib (July 2, 2025), zongertinib (August 8, 2025; 1st-line expansion February 26, 2026), lurbinectedin+atezolizumab (October 2, 2025), sevabertinib (November 19, 2025), zidesamtinib (July 22, 2026); mobosertinib withdrawal (announcement October 2, 2023, authorization revocation July 15, 2024). fda.gov
- Communiqué Amending the Healthcare Implementation Communiqué, July 10, 2025 (SGK SUT update, checkpoint inhibitors).
- Republic of Türkiye Ministry of Health, General Directorate of Public Health. Türkiye Cancer Statistics Report.
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