Non–Small Cell Lung Cancer Clinical Practice Guidelines (2018)

Spanish Society of Medical Oncology

Reviewed and summarized by Medscape editors

December 06, 2018

The guidelines on non–small cell lung cancer (NSCLC) were released on November 17, 2018, by the Spanish Society of Medical Oncology.[1]


Adequate tissue material for histologic diagnosis and molecular testing should be obtained, to allow for individual treatment decisions.

The World Health Organization (WHO) classification for pathologic diagnosis is required, as well as International Association for the Study of Lung Cancer (IASLC) classification of adenocarcinoma.

For therapeutic implications, specific subtyping of NSCLC is strongly recommended.

Molecular testing in stage IV non–squamous cell carcinoma (SCC) NSCLC should include EGFR mutations, ALK rearrangments, and ROS-1 translocations by a validated technique.

In patients progressing on first- or second-generation EGFR tyrosine kinase inhibitor (TKI) therapy, determination of EGFR T790M in plasma or tissue should be performed.

Programmed death–ligand 1 (PD-L1) expression should be tested in all patients with advanced NSCLC at baseline.


Stage I-II

Patients medically fit for surgery should undergo lobectomy or anatomic pulmonary resection plus systematic mediastinal lymph node dissection.

Medically inoperable patients with node-negative NSCLC and tumors ≤5 cm should receive stereotactic ablative radiotherapy (SART).

Adjuvant chemotherapy (four cycles of cisplatin-based chemotherapy) is recommended in stage II; it is not recommended in stage I unless the tumor is > 4 cm.

Postoperative radiotherapy (PORT) is not indicated in completely resected stage I–II disease.

Stage III

Patients with completely resected disease should receive adjuvant chemotherapy (four cycles of cisplatin-based combination regimen) ± PORT.

Potentially resectable disease should be treated with resection followed by adjuvant chemotherapy, or by induction chemotherapy or chemoradiotherapy followed by surgery.

Unresectable stage III disease in medically fit patients should be treated with concurrent chemoradiotherapy (cisplatin-based combination), or with sequential chemoradiotherapy if concurrent treatment is not feasible; prophylactic cranial irradiation is not indicated. Treat with durvalumab if no progressive disease occurs after concurrent chemoradiotherapy.

Stage IV without driver mutations—first-line therapy

PD-L1 ≥ 50% - Pembrolizumab

PD-L1 < 50% or unknown – Platinum-based chemotherapy based on tumor histology

SCC - Platinum-based doublets (four to six cycles); immunotherapy (atezolizumab or pembrolizumab) and carboplatin plus paclitaxel or nab-paclitaxel)

Non-SCC - Platinum-based doublet: cisplatin/pemetrexed has more efficacy and less toxicity than cisplatin/gemcitabine; bevacizumab can be added to a platinum doublet if there are no contraindications. Pemetrexed is recommended for maintenance therapy. Alternatively, immunotherapy (atezolizumab or pembrolizumab) plus standard chemotherapy may be used.

Performance status (PS) 2 – Combination therapy, single-agent therapy, or best supportive care

PS 3-4 – Best supportive care

Stage IV without driver mutations—second-line therapy

PS 0–2, no prior immunotherapy - Pembrolizumab (if PD-L1 ≥1%), nivolumab, or atezolizumab

PS 0–2, prior immunotherapy - Platinum doublets

PS 0–2, contraindication for immunotherapy, or prior immunotherapy + chemotherapy - Docetaxel–nintedanib (non-SCC), docetaxel (SCC, non-SCC), pemetrexed (non-SCC)

PS 0–2, prior immunotherapy alone - Platinum doublets

PS 3–4 - Best supportive care

Stage IV with driver mutations

EGFR mutation – EGFR TKI: Erlotinib, gefitinib, afatinib, dacomitinib, osimertinib (also indicated for brain metastasis)

Progression on EGFR TKI: In T790 M–positive disease, osimertinib (if not previously given); in T790 M–negative disease, platinum-based chemotherapy

ALK mutation – First-line ALK TKI: alectinib, brigatinib, crizotinib or ceritinib

Progression on crizotinib: Ceritinib, alectinib, or brigatinib

Brain metastasis: Alectinib, brigatinib, or lorlatinib

ROS-1 mutation: Crizotinib

B-RAF V600 mutation: Dabrafenib plus trametinib

Oligometastatic disease: Local ablative strategies and TKI continuation if clinical benefit is still retained (if actionable mutation)


After curative-intent surgery: Medical history, physical examination, and spiral chest CT scan every 6–12 months for 2 years and annually thereafter

After SART: Medical history, physical examination, and spiral chest CT scan every 6 months for 3 years and annually thereafter; PET–CT ± biopsy if recurrence is suspected

Advanced disease: Early palliative care, with evaluation of response every 6–12 weeks

For more information, see Non-Small Cell Lung Cancer.

For more Clinical Practice Guidelines, please go to Guidelines.


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