Treatment

Curative treatment for localised non-small cell carcinoma (NSCLC) i.e. squamous, adenocarcinoma or large cell carcinoma, is surgical excision - lobectomy or pneumonectomy.

NICE recommend (1):

Non-small cell lung cancer:

Treatments with curative intent

Surgery:

• surgery with curative intent for non-small-cell lung cancer
  • open or thoracoscopic lobectomy as the treatment of first choice
  • hilar and mediastinal lymph node sampling or en bloc resection must be performed for all people having surgery with curative intent
    • if patient with T3 NSCLC with chest wall involvement who are having surgery, aim for complete resection of the tumour using either extrapleural or en bloc chest wall resection
  • lobectomy
    • for people with NSCLC who are well enough and for whom treatment with curative intent is suitable, offer lobectomy (either open or thoracoscopic)
  • bronchoangioplastic surgery, bilobectomy or pneumonectomy
    • more extensive surgery (bronchoangioplastic surgery, bilobectomy, pneumonectomy) is indicated only when needed to obtain clear margins
  • radiotherapy or sublobar resection
    • if stage I-IIa (T1a-T2b, N0, M0) NSCLC and decline lobectomy/contraindicated, offer radical radiotherapy with SABR or sublobar resection

Chemotherapy after surgery

• postoperative chemotherapy should be considered for people with good performance status (WHO 0 or 1) and T1a-4 N1-2 M0 NSCLC
• postoperative chemotherapy should be considered for people with good performance status (WHO 0 or 1) and T2b-4 N0, M0 NSCLC with tumours greater than 4 cm in diameter
• cisplatin-based combination chemotherapy regimen for adjuvant chemotherapy

Radiotherapy:

• if stage I-IIa (T1a-T2b, N0, M0) NSCLC who decline lobectomy or in whom it is contraindicated, offer radical radiotherapy with SABR or sublobar resection
• if stage I-IIa (T1a-T2b N0, M0) NSCLC who decline surgery or in whom any surgery is contraindicated, offer SABR. If SABR is contraindicated, offer either conventional or hyperfractionated radiotherapy
• for eligible people with stage IIIa NSCLC who cannot tolerate or who decline chemoradiotherapy (with or without surgery), consider radical radiotherapy (either conventional or hyperfractionated)
• for eligible people with stage IIIb NSCLC who cannot tolerate or who decline chemoradiotherapy, consider radical radiotherapy (either conventional or hyperfractionated).

If using SABR, follow the SABR Consortium guidance on fractionation. If conventionally fractionated radical radiotherapy is used, offer either:

• 55 Gy in 20 fractions over 4 weeks or
• 60-66 Gy in 30-33 fractions over 6-6 1/2 weeks. All people should have pulmonary function tests (including lung volumes and transfer factor) before radical radiotherapy for NSCLC.

Chemoradiotherapy

• chemoradiotherapy should be considered for people with stage II or III NSCLC that are not suitable for or decline surgery. Balance potential benefit in survival with the risk of additional toxicities.

Chemoradiotherapy and surgery

• if operable stage IIIa-N2 NSCLC and can have surgery and are well enough for multimodality therapy, consider chemoradiotherapy with surgery
• chemoradiotherapy with surgery improves progression-free survival
• chemoradiotherapy with surgery may improve overall survival.
• For people with stage IIIa-N2 NSCLC who are having chemoradiotherapy and surgery, ensure that their surgery is scheduled for 3 to 5 weeks after the chemoradiotherapy.

Pancoast tumours

• treat in the same way as other types of NSCLC. Offer multimodality therapy according to resectability, stage of the tumour and performance status of the person

Small cell lung cancer:

Early-stage

• surgery should be considered in people with early-stage SCLC (T1-2a, N0, M0).

Limited disease

• limited-stage disease SCLC (broadly corresponding to T1-4, N0-3, M0)
  • offer 4 to 6 cycles of cisplatin-based combination chemotherapy
  • consider substituting carboplatin in people with impaired renal function, poor performance status (WHO 2 or more) or significant comorbidity

First-line treatment for extensive-stage disease

• platinum-based combination chemotherapy should be offered to people with extensive-stage disease SCLC (broadly corresponding to T1-4, N0-3, M1a/b -including cerebral metastases) if they are fit enough
• consider thoracic radiotherapy with prophylactic cranial irradiation for people with extensive-stage disease SCLC who have had a partial or complete response to chemotherapy within the thorax and at distant sites

Systemic anti-cancer therapy (SACT) for advanced non-small-cell lung cancer

Squamous non-small-cell lung cancer

• no targetable mutations, PD-L1 less than 50%
• no targetable mutations, PD-L1 50% or more
• RET fusion positive, PD-L1 less than 50%
• RET fusion positive, PD-L1 50% or more
• NTRK fusion positive, PD-L1 less than 50%
• NTRK fusion positive, PD-L1 50% or more
• KRAS G12C positive, PD-L1 less than 50%
• KRAS G12C positive, PD-L1 50% or more
• METex14 skipping alteration, PD-L1 less than 50%
• METex14 skipping alteration, PD-L1 50% or more

Non-squamous non-small-cell lung cancer

• no targetable mutations, PD-L1 less than 50%
• no targetable mutations, PD-L1 50% or more
• EGFR-TK pos
• ALK positive
• ROS-1 positive
• RET fusion positive, PD-L1 less than 50%
• RET fusion positive, PD-L1 50% or more
• NTRK fusion positive, PD-L1 50% or more
• KRAS G12C positive, PD-L1 less than 50%
• KRAS G12C positive, PD-L1 50% or more
• METex14 skipping alteration, PD-L1 less than 50%
• METex14 skipping alteration, PD-L1 50% or more

For detailed guidance then see NICE (March 2024). Lung cancer: diagnosis and management

Notes:

• spirometry and transfer factor (TLCO) must be undertaken in all people being considered for treatment with curative intent.

Reference:

• NICE (March 2024). Lung cancer: diagnosis and management
• NICE (July 2019). Pembrolizumab for untreated PD-L1-positive metastatic non-small-cell lung cancer
• NICE (June 2021). Atezolizumab monotherapy for untreated advanced non-small-cell lung cancer