Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†

M. Frh 2 3 D. De Ruysscher 1 2 S. Popat 0 2 L. Crin 2 6 S. Peters 2 5 E. Felip 2 4 on behalf of the ESMO Guidelines Working Group 2 0 Royal Marsden Hospital , London, UK 1 Radiation Oncology, University Hospitals Leuven/KU Leuven , Belgium 2 L. Taddei 4, CH-6962 Viganello-Lugano, Switzerland 3 Department of Medical Oncology and Hematology , Kantonsspital St Gallen, Switzerland 4 Medical Oncology Service, Vall d'Hebron University Hospital , Barcelona, Spain 5 Dpartement d'Oncologie, Centre Hospitalier Universitaire Vaudois , Lausanne, Switzerland 6 Department of Oncology, Hospital Santa Maria della Misericordia , Sant Andrea delle Fratte, Perugia, Italy These Clinical Practice Guidelines are endorsed by the Japanese Society of Medical Oncology (JSMO) incidence and epidemiology - An estimated 1.6 million new lung cancers are diagnosed worldwide each year. The highest incidence rates in males are observed in Central/Eastern and Southern Europe (57 and 49 per 100 000, respectively), whereas in women the highest rates are found in Northern Europe (36 per 100 000) [1]. Five-year survival rates of lung cancer patients have only slightly improved during the past decade but remain low at 10% [2]. Small-cell lung cancer (SCLC) originates from neuroendocrine-cell precursors and is characterised by its rapid growth, its high response rates to both chemotherapy and radiotherapy and development of treatment resistance in patients with metastatic disease. In the Western world, the proportion of patients with SCLC has decreased to 13% [3]. Virtually all patients have a history of tobacco use. Therefore, smoking habits are closely linked to incidence, which varies across different populations. In addition, the new description of large-cell neuroendocrine tumours in the 1990s, which may have been summarised previously as SCLC, possibly has contributed to the decline. Smoking cessation not only reduces the risk of developing SCLC but also has been shown to decrease the risk of death of patients with localised SCLC by almost 50% [4]. Only one-third of the patients are diagnosed with localised disease, where cure is the treatment goal. Due to the aggressive natural course, screening by radiological imaging is unlikely to lead to a reduction of mortality, and smoking prevention will undoubtedly remain the primary and most important intervention to further decrease mortality [5]. Approved by the ESMO Guidelines Working Group: February 2002, last update May 2013. This publication supersedes the previously published versionAnn Oncol 2010; 21 (Suppl. 5): v120v125. diagnosis and pathology/molecular biology Pathological diagnosis should be made according to the World Health Organisation (WHO) classification using morphology (uniform round to spindled-shaped small cells, sparse cytoplasm, high mitotic index, necrotic areas). Immunohistochemistry to confirm the diagnosis of SCLC (synaptophysin, chromogranin A, CD56, thyroid transcription factor 1 and MIB-1) is not mandatory, but should be used in case of any doubt (e.g. in case of pronounced crush artefacts). Due to its frequent central localisation within the chest, biopsies may best be obtained by bronchoscopy. Other methods include mediastinoscopy, endobronchial ultrasound (EBUS), endoscopic ultrasound, transthoracic needle aspiration or even thoracoscopy if necessary. A biopsy from a metastatic lesion may be the preferred option if the location of the metastasis is easily and safely accessible to biopsy, as this will also pathologically stage the patient (e.g. liver, skin). staging and risk assessment The prognosis of SCLC strongly depends on the tumour stage. The new tumour-node-metastasis (TNM) version 7 staging system according to the Union for International Cancer Control (UICC) as adopted for non-small-cell lung cancer should also be used for SCLC [I, A] [6,7] (See Tables 1 and 2). This classification should replace the former 1989 International Association for the Study of Lung Cancer (IASLC) staging system, which defined limited stage as tumour being confined to one hemithorax with regional lymph node metastasis including both ipsilateral and contralateral hilar, supraclavicular and mediastinal nodes, as well as ipsilateral pleural effusion. The current TNM staging system is based on 8088 SCLC patients and provides better prognostic information and more precise nodal staging, which is required for conformal radiation techniques and intensity-modulated radiation therapy. The The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: . Positive cytology only 3 cm 2 cm >2 to 3 cm Main bronchus 2 cm from carina invades visceral pleura, partial atelectasis >35 cm >57 cm >7 cm; chest wall, diaphragm, pericardium, mediastinal pleura, main bronchus <2 cm from carina, total atelectasis, separate nodule(s) in the same lobe Mediastinum, heart, great vessels, carina, trachea, esophagus, vertebra; separate tumour nodule(s) in a different ipsilateral lobe Ipsilateral peribronchial, ipsilateral hilar Subcarinal, ipsilateral mediastinal Contralateral mediastinal or hilar, scalene or supraclavicular Distant metastasis Separate tumour nodule(s) in a contralateral lobe; pleural nodules or malignant pleural, or pericardial effusion Distant metastasis Lababede O, Meziane M, Rice T. Seventh Edition of the Cancer Staging Manual and Stage Grouping of Lung Cancer. Chest 2011; 139: 183189. Reproduced with permission from the American College of Chest Physicians. Lababede O, Meziane M, Rice T. Seventh Edition of the Cancer Staging Manual and Stage Grouping of Lung Cancer. Chest 2011; 139: 183189. Reproduced with permission from the American College of Chest Physicians. former term limited stage would now include T1-4, N0-3 M0 tumours, whereas metastatic tumours encompass former extensive stage patients. In addition, T1 or T2 N0 or N1 M0 tumours ( previously described as very limited stage) were identified as a group with a more favourable outcome compared with patients with N2 or N3 disease. Initial assessment should encompass medical history including smoking history, physical examination, complete blood count including differential count, liver enzymes, sodium, potassium, calcium, glucose, lactate dehydrogenase levels and renal function tests, and in the case of localised disease, lung function tests. An initial computed tomography (CT) scan with contrast of the chest and abdomen is recommended. If the metastatic stage is not obvious on the CT scan or clinical findings suggest bone or brain involvement, further imaging with bone scintigraphy and CT or magnetic resonance imaging (MRI) of the brain are recommended. In case of abnormal blood count or signs of bloodbone marrow barrier rupture (e.g. peripheral blood erythroblasts), a bone marrow aspiration and biopsy may be indicated, particularly in patients with otherwise absent metastases [V, C (...truncated)