This article appears in the following Annals of Oncology issue: ESMO Clinical Recommendations [View the issue table of contents]
ESMO clinical recommendations |
Non-small-cell lung cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up
1 Onkologie Schaffhausen, Schaffausen, Switzerland
2 Medical Oncology Service, Vall d'Hebron University Hospital, Barcelona, Spain
* Correspondence to: ESMO Guidelines Working Group, ESMO Head Office, Via L. Taddei 4, CH-6962 Viganello-Lugano, Switzerland; E-mail: clinicalrecommendations{at}esmo.org
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incidence |
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 Top incidence diagnosisstaging and risk assessmentsecond-line therapyresponse evaluationfollow-upnotereferences |
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The crude incidence of lung cancer in the European Union is 52.5/100 000 per year, the mortality 48.7/100 000 per year. Among men the rates are 82.5 and 77.0/100 000 per year, among women 23.9 and 22.3/100 000 per year, respectively. Non-small-cell lung cancer (NSCLC) accounts for 80% of all cases. About 90% of lung cancer mortality among men (and 80% among women) is attributable to smoking.
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diagnosis |
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Topincidencediagnosisstaging and risk assessmentsecond-line therapyresponse evaluationfollow-upnotereferences |
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Pathological diagnosis should be made according to the WHO classification. The main NSCLC tumor groups are adenocarcinoma, squamous cell carcinoma and large-cell carcinoma. Histological or cytological specimens can be obtained from the primary tumor, lymph node or distant metastases or malignant effusions. The least invasive procedure should be used.
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staging and risk assessment |
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Topincidencediagnosisstaging and risk assessmentsecond-line therapyresponse evaluationfollow-upnotereferences |
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- Complete history and physical examination, CT scan of the chest and upper abdomen.
- MRI of the brain if abnormal neurologic findings (to be substituted by CT scan if MRI not available).
- Bone scan in the presence of bone pain, elevated serum calcium, or elevated alkaline phosphatase levels.
patients with potentially curative treatment
- Whole-body FDG-PET scan if available. In case of pathological mediastinal lymph node uptake, biopsy of an abnormal node is recommended (required if positivity would affect curative treatment, i.e. N3 lymph node).
- If FDG-PET not available or result inconclusive: biopsy of mediastinal lymph nodes
1 cm in short axis.
- Biopsy of mediastinal lymph nodes can be obtained by mediastinoscopy, transbronchial needle aspiration, ultrasound-guided bronchoscopy with fine needle aspiration, and /or endoscopic esophageal ultrasound-guided fine needle aspiration.
- MRI of the brain for clinical stage III patients (to be substituted by CT scan if MRI not available) planned for definitive local treatment.
- Bone scan if FDG-PET not available for clinical stage III patients planned for definitive local treatment.
- In patients with a single metastatic lesion on imaging studies, biopsy should be attempted to prove metastatic disease if otherwise curatively treatable.
- Cytology of pleural / pericardial effusions in patients otherwise curatively treatable.
Patients with NSCLC shall be staged according to the UICC 6 system and be grouped into the risk categories shown in Table 1.
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treatment of localized disease
- Surgical resection in functionally fit patients (lobectomy/pneumonectomy plus systematic mediastinal lymph node sampling or lymphadenectomy).
- Cisplatin-based adjuvant combination chemotherapy is recommended in stage II and IIIA [I, A], and can be considered in selected stage IB patients (T > 4 cm).
- Preoperative cisplatin-based combination chemotherapy can be considered in patients with stage IIIA–N2 disease [II, B].
- Postoperative radiotherapy may be considered in patients not radically resected.
- Postoperative radiotherapy is not recommended for patients with radically resected Stage I and II disease [I, A] and can be considered for patients with resected stage IIIA disease.
- Curative conformal radiotherapy as a single modality is to be considered in patients unfit for standard surgery.
- Platinum-based chemotherapy, preferably concurrent with thoracic radiotherapy, is the standard treatment for selected patients with locally advanced, unresectable stage III NSCLC and adequate pulmonary function.
treatment of stage IV disease
- First-line treatment with a two-drug, platinum-based chemotherapy combined with a new agent (vinorelbine, gemcitabine, taxanes, or pemetrexed in patients with predominantly non-squamous cell carcinoma histology) is considered the standard treatment in patients with good performance status [I, A]. Non-platinum based combination chemotherapy of new agents can be considered alternatively.
- In the first-line treatment of selected, advanced, non-squamous NSCLC patients, one randomized trial showed that the combination of bevacizumab with paclitaxel-carboplatin achieved longer progression-free survival and overall survival than chemotherapy alone. In another, randomized trial the gemcitabine-cisplatin-bevacizumab combination obtained longer progression-free survival than gemcitabine-cisplatin, without differences in median survival.
- In a randomized trial, the addition of cetuximab to cisplatin-vinorelbine as first-line therapy has shown a modest improvement in overall survival, but not in progression-free survival, in EGFR immunohistochemistry positive NSCLC patients.
- In the first-line treatment of patients with tumors harboring EGFR mutation, EGFR tyrosine kinase inhibitors should be considered, pending results of ongoing randomized trials.
- In frail elderly patients and in patients with performance status 2, single-agent chemotherapy might be considered [II, B].
- Timing and duration of palliative first-line treatment: chemotherapy should be initiated while the patient is in good performance status. The role of chemotherapy beyond four to six cycles has to be established.
- Resection of single metastases can be considered in selected cases [III, B].
- For the palliative treatment of multiple brain metastases, whole brain radiotherapy is recommended.
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second-line therapy |
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Topincidencediagnosisstaging and risk assessmentsecond-line therapyresponse evaluationfollow-upnotereferences |
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Second-line systemic treatment (docetaxel, erlotinib, or pemetrexed in patients with predominantly non-squamous histology) should be considered in appropriately selected patients [I, A].
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response evaluation |
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Topincidencediagnosisstaging and risk assessmentsecond-line therapyresponse evaluationfollow-upnotereferences |
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Response evaluation is recommended after two or three cycles of chemotherapy by repetition of the initial radiographic tests showing tumor lesions.
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follow-up |
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Topincidencediagnosisstaging and risk assessmentsecond-line therapyresponse evaluationfollow-upnotereferences |
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The optimal approach to post-treatment management of patients with NSCLC, including the role of radiologic evaluations, is controversial. For patients receiving intent-to-cure treatment, history and physical examination should be performed every 3–6 months during the first 2 years, and every 6–12 months thereafter and radiologic evaluations should be considered at these time points.
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note |
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Topincidencediagnosisstaging and risk assessmentsecond-line therapyresponse evaluationfollow-upnotereferences |
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Levels of evidence [I–V] and grades of recommendation [A–D] as used by the American Society of Clinical Oncology are given in square brackets. Statements without grading were considered justified standard clinical practice by the expert authors and the ESMO faculty.
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footnotes |
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Approved by the ESMO Guidelines Working Group: February 2002, last update August 2008. This publication supercedes the previously published version–Ann Oncol 2008; 19 (Suppl 2): ii39–ii40.
Conflict of interest: The authors have reported no conflicts of interest
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references |
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Topincidencediagnosisstaging and risk assessmentsecond-line therapyresponse evaluationfollow-upnotereferences |
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