II. Epidemiology

  1. Lung Cancer mortality dwarfs other causes of cancer death for the last 50 years

III. Types Non-Small Cell Lung Cancer (75% of Lung Cancers)

  1. Squamous Cell Carcinoma (25%)
    1. Late metastases
    2. Central endobronchial lesions
    3. Presents with Hemoptysis, Pneumonia, Atelectasis
  2. Adenocarcinoma (40%)
    1. Peripheral lesions
    2. Early metastases
    3. Associated with underlying lung disease
    4. Types
      1. Acinar
      2. Bronchioalveolar
      3. Papillary
      4. Solid carcinoma with mucus formation
  3. Large cell carcinoma (10%)
    1. Poorly differentiated tumors
    2. Large peripheral lesions
    3. Types
      1. Neuroendocrine type
      2. Basaloid type
      3. Lymphoepithelial-like
      4. Rhabdoid Phenotype
  4. Other uncommon Lung Cancers (<5 of Lung Cancers)
    1. Adenosquamous carcinoma
    2. Carcinoid
    3. Bronchial gland carcinoma

IV. Evaluation: Resectable Disease

  1. Surgical Lymph Node evaluation is critical
  2. Step 1: General testing
    1. Complete History and Physical
    2. Pathology review
    3. CT chest and Abdomen
    4. Complete Blood Count
    5. Chemistry panel
    6. Tobacco Cessation
  3. Step 2: Stage Peripheral T1-2NO or Central T1-2N0
    1. Step 1 testing and
    2. Pulmonary Function Tests
    3. Bronchoscopy
    4. Mediastinoscopy
    5. PET Scan
  4. Step 3: Stage T1-2N1 or T1-3N2
    1. Step 2 testing and
    2. Brain MRI (for stage 2B, MRI only if non-squamous cell cancer)
  5. Step 4: Stage T1-2N1 or T1-3N2
    1. Step 3 testing and
    2. Spine MRI and thoracic inlet MRI

V. Staging

  1. Resources
    1. Staging Calculator
      1. http://staginglungcancer.org/calculator
  2. Stage IA: Local (T1N0M0)
    1. Characteristics
      1. Primary tumor <3 cm
      2. No nodal involvement
      3. No distant metastases
    2. Prognosis
      1. Surgical cure rate: 80%
  3. Stage IB: Local (T2N0M0)
    1. Characteristics
      1. Primary tumor >3 cm
      2. No nodal involvement
      3. No distant metastases
    2. Prognosis
      1. Surgical cure rate: 60%
  4. Stage II: Locally advanced (T2N1M0, T3N0M0)
    1. Characteristics
      1. Primary tumor any size and confined to the lung
      2. Ipsilateral Bronchial or hilar node involvement
      3. No distant metastases
    2. Prognosis
      1. Surgical cure rate: 30 to 40%
  5. Stage IIIA: Locally advanced (T1N2M0, T2N2M0, T3N1-2M0)
    1. Characteristics
      1. Ipsilateral mediastinal Lymph Node involvement or
      2. Primary tumor with local extension
        1. Extension to pleura or chest wall or
        2. Extension to Pericardium or
        3. Extension to diaphragm or
        4. Extension to within 2 cm of carina
    2. Prognosis
      1. Surgical cure rate: 10 to 20%
  6. Stage IIIB: Advanced (T4N1-3M0)
    1. Characteristics
      1. Contralateral Lymph Node involvement or
      2. Primary tumor with local invasion
        1. Tumor invasion of mediastinum
        2. Malignant Pleural Effusion
    2. Prognosis
      1. Surgical cure rate: <5%
  7. Stage IV: Advanced (T1-4N1-3M1)
    1. Characteristics: Distant Metastases
    2. Prognosis
      1. Surgical cure rate: <5%

VI. Management: Approach by Stage

  1. Stage I
    1. Surgical resection
  2. Stage II
    1. Surgical resection and Adjuvant Chemotherapy
  3. Stage III
    1. Eradicate intrathoracic cancer
    2. Limit subsequent metastases with Chemotherapy and radiation
  4. Stage IV or low functional status
    1. Multidisciplinary management tailored to pathology and patient functional status
    2. Palliative Care (initiate early for optimal effects on quality of life)

VII. Management: Approach for Metastases

  1. Brain Metastases
    1. Brain metastases <3 lesions
      1. Stereotactic Radiotherapy with or without surgical resection
    2. Brain metastases >=3 lesions
      1. Whole brain radiation
  2. Bone Metastases
    1. Radiotherapy and Bisphosphonates to reduce pain and Fracture risk

VIII. Management: Surgical Resection

  1. Most effective Non-Small Cell Lung Cancer management
  2. Long-term Cancer Survivorship associated with resection
  3. Recurrence rate following resection: 50%
  4. Indicated in only 30% of patients (I, II, IIIA)
    1. See evaluation above
    2. No significant distant metastases
    3. Locally resectable disease within the chest

IX. Management: Adjuvant Chemotherapy

  1. Standard of care for resected stage II-IIIA Non-Small Cell Lung Cancer if medically stable
  2. Cisplatin-based regimen for 12 weeks

X. Management: Post-operative radiation (PORT)

  1. Indicated for residual disease following resection
  2. Post-operative radiation follows adjuvant Chemotherapy

XI. Management: Immunotherapy

  1. Indications for genetic and Immunotherapy testing
    1. Nonsquamous NSCLC or mixed histology
    2. Small volume biopsy
  2. Markers
    1. PD-L1 (Programmed Death Ligand 1)
      1. Most important Tumor Marker in NSCLC
      2. Expression percentage (0 to 50) directs Immunotherapy strategy
    2. Genetic Mutations
      1. Anaplastic Lymphoma kinase
      2. BRAF V600E
      3. Epidermal Growth Factor Receptor
      4. MET ex 14 Skipping
      5. NTRK gene fusion
      6. RET
      7. ROS1
  3. Immunotherapy Agents used in NSCLC (Partial List as of 2022, many others are used for genetic mutations)
    1. Pembrolizumab (Keytruda)
    2. Pemetrexed (Alimta)
    3. Atezolizumab (Tecentriq)
    4. Bevacizumab (Avastin)
    5. Cemiplimab (Libtayo)
    6. Nivolumab (Opdivo)
    7. Ipilimumab (Yervoy)
    8. Topotecan (Hycamtin)
    9. Lurbinectedin (Zepzelca)

XII. Management: Follow-up surveillance

  1. Routine physical examination every 4-6 months for 2 years and then annually
  2. Chest CT
    1. Spiral contrast- enhanced CT every 4-6 months for 2 years, then
    2. Noncontrast-enhanced CT annually thereafter (controversial)

XIII. Prognosis

  1. Five Year Survival (2017)
    1. Localized NSCLC: 59%
    2. Distant Metastases: 5.8%

XIV. Prevention

  1. See Lung Cancer
  2. Tobacco Cessation is critical

Images: Related links to external sites (from Bing)

Related Studies

Ontology: Non-Small Cell Lung Carcinoma (C0007131)

Definition (MSH) A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.
Definition (NCI_NCI-GLOSS) A group of lung cancers that are named for the kinds of cells found in the cancer and how the cells look under a microscope. The three main types of non-small cell lung cancer are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Non-small cell lung cancer is the most common kind of lung cancer.
Definition (NCI) A group of at least three distinct histological types of lung cancer, including squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Non-small cell lung carcinomas have a poor response to conventional chemotherapy.
Definition (CSP) heterogeneous group of lung cancers which include epidermoid or squamous carcinomas, adenocarcinomas, and large cell carcinomas.
Concepts Neoplastic Process (T191)
MSH D002289
SnomedCT 254637007
English Carcinoma, Non Small Cell Lung, Non Small Cell Lung Carcinoma, Non-Small-Cell Lung Carcinoma, Carcinoma, Non-Small-Cell Lung, Carcinomas, Non-Small-Cell Lung, Lung Carcinoma, Non-Small-Cell, Lung Carcinomas, Non-Small-Cell, Non-Small-Cell Lung Carcinomas, NSCLC - Non-small cell lng can, NONSMALL CELL LUNG CANCER, NONSMALL CELL LUNG CARCINOMA, non-small cell carcinoma of lung (diagnosis), non-small cell carcinoma of lung, Carcinoma, Non-Small-Cell Lung [Disease/Finding], Non-Small Cell Lung Cancer, Carcinoma, Non-Small Cell Lung, carcinoma cell lung non-small, lung carcinoma non small cell, lung cancer non-small cell, non small cell lung carcinoma, cancer cell lung non-small, cancer cells lung non small, carcinoma cell lung non small, nsclc, cancer cell lung non small, lung cancer non small cell, small non cell lung cancer, non small cell lung cancer, Non-Small Cell Lung Carcinoma, Nonsmall Cell Lung Cancer, Non-small cell lung cancer NOS, Non-small cell lung cancer, NOS, NSCLC - Non-small cell lung cancer, Non-small cell lung cancer, Non-small cell lung cancer (disorder), nonsmall cell lung cancer, lung cancer, nonsmall cell, non-oat cell lung cancer, non-small cell lung cancer, Lung cancer, non-small cell, NSCLC, NSCLC - Non-Small Cell Lung Cancer, Non Small Cell Lung Cancer NOS, Non-Small Cell Cancer of Lung, Non-Small Cell Cancer of the Lung, Non-Small Cell Carcinoma of Lung, Non-Small Cell Carcinoma of the Lung
Italian Cancro del polmone non a piccole cellule, Cancro del polmone non a piccole cellule NAS, Carcinoma del polmone non a piccole cellule
Dutch niet-kleincellige longkanker NAO, niet-kleincellige longkanker, Carcinoom, niet-kleincellig long-, Longcarcinoom, niet-kleincellig, Niet-kleincellig longcarcinoom
French Cancer bronchopulmonaire « non à petites cellules » SAI, Cancer du poumon non à petites cellules, CPNPC, Carcinome du poumon non à petites cellules, CBNPC, Cancer bronchopulmonaire « non à petites cellules », Carcinome bronchique non à petites cellules, Carcinome pulmonaire non à petites cellules, Cancer bronchique non à petites cellules, Cancer broncho-pulmonaire non à petites cellules, Cancer bronchopulmonaire non à petites cellules, Cancer pulmonaire non à petites cellules
German nichtkleinzelliges Lungenkarzinom NNB, nicht-kleinzelliges Lungenkarzinom, Karzinom, nichtkleinzelliges Lungen-, Nichtkleinzelliges Lungenkarzinom
Portuguese Cancro pulmonar de células não-pequenas NE, Câncer Pulmonar de Células não Pequenas, Carcinoma de Pulmão de não Pequenas Células, Carcinoma de Pulmão de Células não Pequenas, Cancro pulmonar de células não-pequenas, Carcinoma Pulmonar de Células não Pequenas, Carcinoma Pulmonar de não Pequenas Células
Spanish Cáncer de pulmón de células no pequeñas NEOM, cáncer pulmonar de células no pequeñas (trastorno), cáncer pulmonar de células no microcíticas, cáncer pulmonar de células no microcíticas (trastorno), cáncer pulmonar de células no pequeñas, Cáncer Pulmonar de Células no Pequeñas, Carcinoma Pulmonar no Microcítico, Cáncer de pulmón de células no pequeñas, Carcinoma Pulmonar de Células no Pequeñas, Carcinoma de Pulmón de Células no Pequeñas
Swedish Lungkarcinom, icke-småcelligt
Czech karcinom plic nemalobuněčný, Nemalobuněčné maligní nádorové onemocnění plic NOS, Nemalobuněčné maligní nádorové onemocnění plic
Finnish Keuhkon ei-pienisoluinen karsinooma
Russian NEMELKOKLETOCHNAIA KARTSINOMA LEGKOGO, KARTSINOMA NEMELKOKLETOCHNAIA LEGKOGO, LEGKIKH KARTSINOMA NEMELKOKLETOCHNAIA, КАРЦИНОМА НЕМЕЛКОКЛЕТОЧНАЯ ЛЕГКОГО, ЛЕГКИХ КАРЦИНОМА НЕМЕЛКОКЛЕТОЧНАЯ, НЕМЕЛКОКЛЕТОЧНАЯ КАРЦИНОМА ЛЕГКОГО
Japanese ヒショウサイボウハイガンNOS, ヒショウサイボウハイガン, 非小細胞肺癌NOS, 肺癌-非小細胞, 癌-非小細胞肺, 非小細胞肺癌, 肺非小細胞癌, 非小細胞性肺癌
Croatian KARCINOM NEMALIH STANICA PLUĆA
Polish Rak płuc nieowsianokomórkowy, Rak płuc niedrobnokomórkowy
Hungarian Nem-kis sejtes tüdőrák, Nem-kis sejtes tüdőrák k.m.n.
Norwegian Ikke-småcellet lungekarsinom, Ikke-småcellet lungekreft, Lungekarsinom, ikke-småcellet

Ontology: Squamous cell carcinoma of lung (C0149782)

Definition (NCI) A carcinoma arising from malignant squamous bronchial epithelial cells and characterized by the presence of keratinization and/or intercellular bridges. Cigarette smoking and arsenic exposure are strongly associated with squamous cell lung carcinoma.
Concepts Neoplastic Process (T191)
SnomedCT 254634000
English Squamous cell carcinoma lung, SCC-Squam cell carcinoma lung, squamous cell carcinoma of lung (diagnosis), squamous cell carcinoma of lung, cancer cell lung squamous, carcinoma cell lungs squamous, squamous cell carcinoma lung, cancer cells lung squamous, lung cancer squamous cell, cancers cell lung squamous, carcinoma cell lung squamous, lung squamous cell carcinoma, squamous cell cancer lung, cancer cell lungs squamous, squamous cell lung carcinoma, Squamous cell carcinoma of lung stage unspecified, Lung squamous cell carcinoma stage unspecified, Squamous cell lung carcinoma, Epidermoid carcinoma of lung, Squamous cell carcinoma of lung, SCC - Squamous cell carcinoma of lung, Squamous cell carcinoma of lung (disorder), squamous cell lung cancer, epidermoid lung cancer, lung cancer, epidermoid, lung cancer, squamous cell, non-oat cell lung cancer, squamous cell, Epidermoid Cell Carcinoma of Lung, Epidermoid Cell Carcinoma of the Lung, Epidermoid Cell Lung Carcinoma, Squamous Cell Carcinoma of Lung, Squamous Cell Carcinoma of the Lung, Squamous Cell Lung Carcinoma
Czech Dlaždicobuněčný karcinom plic blíže neurčeného stadia, Dlaždicobuněčný karcinom plic
Dutch squameuscelcarcinoom van de long stadium niet-gespecificeerd, squameuscelcarcinoom van de long, longsquameuscelcarcinoom niet-gespecificeerd stadium
French Carcinome épidermoïde pulmonaire stade non précisé, Carcinome épidermoïde du poumon stade non précisé, Carcinome épidermoïde du poumon
German Plattenepithelkarzinom der Lunge, Plattenepithelkarzinom der Lunge Stadium unbekannt, Plattenepithelkarzinom der Lunge Stadium unspezifisch
Hungarian Tüdő squamosus-sejtes carcinomája, Tüdő squamosus sejtes nem meghatározott stádiumú carcinoma, Tüdő squamosus-sejtes carcinomája, stádium nem meghatározott
Italian Carcinoma a cellule squamose del polmone stadio non specificato, Carcinoma a cellule squamose del polmone
Japanese 肺扁平上皮癌, ハイヘンペイジョウヒガン, 肺扁平上皮癌、病期不明, ハイヘンペイジョウヒガンビョウキフメイ
Portuguese Carcinoma pavimentocelular do pulmão, Carcinoma pavimentocelular do pulmão estádio NE, Carcinoma pulmonar pavimentocelular estádio não especificado
Spanish Carcinoma de pulmón de células escamosas, estadio no especificado, Carcinoma de células escamosas de pulmón, Carcinoma de células escamosas de pulmón, estadio no especificado, carcinoma de células escamosas de pulmón (trastorno), carcinoma de células escamosas de pulmón, carcinoma epidermoide de pulmón, carcinoma escamoso de pulmón

Ontology: Adenocarcinoma of lung (disorder) (C0152013)

Definition (NCI) A carcinoma that arises from the lung and is characterized by the presence of malignant glandular epithelial cells. There is a male predilection with a male to female ratio of 2:1. Usually lung adenocarcinoma is asymptomatic and is identified through screening studies or as an incidental radiologic finding. If clinical symptoms are present they include shortness of breath, cough, hemoptysis, chest pain, and fever. Tobacco smoke is a known risk factor.
Concepts Neoplastic Process (T191)
MSH C538231
SnomedCT 254626006
Italian Adenocarcinoma del polmone, Adenocarcinoma del polmone NAS
Dutch longadenocarcinoom NAO, adenocarcinoom long, adenocarcinoom van de long, longadenocarcinoom
French Adénocarcinome pulmonaire, Adénocarcinome pulmonaire SAI, Adénocarcinome du poumon
German Adenokarzinom Lunge, Adenokarzinom der Lunge NNB, Adenokarzinom der Lunge
Portuguese Adenocarcinoma pulmonar NE, Adenocarcinoma do pulmão
Spanish Adenocarcinoma de pulmón NEOM, adenocarcinoma del pulmón (trastorno), adenocarcinoma del pulmón, Adenocarcinoma de pulmón
Japanese 肺腺癌, 肺腺癌NOS, ハイセンガンNOS, ハイセンガン
English ADENOCARCINOMA OF LUNG, adenocarcinoma of lung, adenocarcinoma of lung (diagnosis), Adenocarcinoma lung, Lung adenocarcinoma NOS, Adenocarcinoma of lung (disorder), lung adenocarcinoma, Adenocarcinoma of lung, adenocarcinoma cancer lungs, adenocarcinoma lung, adenocarcinomas lung, of lung adenocarcinoma, adenocarcinoma lung cancer, adenocarcinoma cancer lung, adenocarcinoma lungs, lung cancer adenocarcinoma, Lung adenocarcinoma, Pulmonary adenocarcinoma, adenocarcinoma of the lung, lung cancer, adenocarcinoma, lung, adenocarcinoma of the, non-oat cell adenocarcinoma of the lung, Adenocarcinoma of Lung, Adenocarcinoma of the Lung, Lung Adenocarcinoma
Czech Adenokarcinom plic, Plicní adenokarcinom NOS, Plicní adenokarcinom
Hungarian Tüdő adenocarcinoma k.m.n., Tüdő-adenocarcinoma, Tüdő adenocarcinoma

Ontology: Large cell carcinoma of lung (C0345958)

Definition (NCI) A poorly differentiated non-small cell lung carcinoma composed of large polygonal cells without evidence of glandular or squamous differentiation. There is a male predilection.
Concepts Neoplastic Process (T191)
SnomedCT 254629004
English Anaplastic Lung Carcinoma, Large Cell Undifferentiated Lung Carcinoma, anaplastic carcinoma of lung (diagnosis), large cell carcinoma of lung, anaplastic carcinoma of lung, large cell carcinoma of lung (diagnosis), cancer cells large lung, large cell cancer lung, large cell lung carcinoma, carcinoma cell large lungs, large cell carcinoma lung, lung cancer large cell, carcinoma cell large lung, Large cell lung cancer, Large cell carcinoma of lung, Large cell carcinoma of lung (disorder), large cell lung cancer, anaplastic large cell lung cancer, lung cancer, anaplastic large cell, lung cancer, large cell, lung cancer, undifferentiated large cell, undifferentiated large cell lung cancer, Large Cell Carcinoma of Lung, Large Cell Carcinoma of the Lung, Large Cell Lung Carcinoma
Czech Velkobuněčné maligní nádorové onemocnění plic
Dutch grootcellig longkanker
French Cancer du poumon à grandes cellules
German grosszelliges Lungenkarzinom
Hungarian Nagysejtes tüdőrák
Italian Cancro del polmone a grandi cellule
Japanese 肺大細胞癌, ハイダイサイボウガン
Portuguese Cancro pulmonar de grandes células
Spanish Cáncer de pulmón de células grandes, carcinoma de células grandes de pulmón (trastorno), carcinoma de células grandes de pulmón

Ontology: Non-Small Cell Adenocarcinoma (C1335060)

Concepts Neoplastic Process (T191)
English Non-Small Cell Adenocarcinoma, Nonsmall Cell Adenocarcinoma