Introduction
Methodology
Pathological diagnosis
Initial evaluation and staging
T | N | M | AJCC stage |
---|---|---|---|
TX | N0 | M0 | Occult |
Tis | N0 | M0 | 0 |
T1a | N0 | M0 | IA1 |
T1b | N0 | M0 | IA2 |
T1c | N0 | M0 | IA3 |
T2a | N0 | M0 | IB |
T2b | N0 | M0 | IIA |
T1a–T2b | N1 | M0 | IIB |
T3 | N0 | M0 | |
T1a–T2b | N2 | M0 | IIIA |
T3 | N1 | M0 | |
T4 | N0/N1 | M0 | |
T1a–T2b | N3 | M0 | IIIB |
T3–T4 | N2 | M0 | |
T3–T4 | N3 | M0 | IIIC |
Any T | Any N | M1a/M1b | IVA |
Any T | Any N | M1c | IVB |
Limited stage
Stage I–IIA (T1–T2, N0, M0)
Stage IIB–IIIC (T3–4, N0, M0; T 1–4, N1–3, M0)
Extensive stage
First-line treatment
Combined chemotherapy and immunotherapy
Chemotherapy
Carboplatin or cisplatin plus etoposide
Alternative regimens to platinum–etoposide
Camptothecin-based regimens
Epirubicin plus cisplatin
Duration of treatment
Radiotherapy in ES-SCLC
Prophylactic cranial irradiation (PCI) in ES-SCLC
Treatment of brain metastases
Consolidative thoracic radiation therapy
Second and successive lines in ES-SCLC
Treatment of fragile and elderly patients
Follow-up
Systemic regimens for LS-SCLC Chemotherapy should be administered up to a maximum of 4–6 cycles | |
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Preferred regimen Cisplatin 75 mg/m2 day 1 and etoposide 100 mg/m2 days 1–3, every 21 days Alternative regimens Cisplatin 25 mg/m2 day 1–3 and etoposide 100 mg/m2 days 1–3, every 21 days Carboplatin AUC 5–6 day 1 and etoposide 100 mg/m2 days 1–3, every 21 days. |
Systemic regimens for ES-SCLC first line | |
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Preferred regimens: combination of chemotherapy + immunotherapy Carboplatin AUC 5 day 1 and etoposide 100 mg/m2 days 1, 2, 3 and atezolizumab 1200 mg day 1 every 21 days × 4 cycles followed by maintenance atezolizumab 1200 mg day 1, every 21 days (IA) Carboplatin AUC 5–6 day 1 and etoposide 80–100 mg/m2 days 1, 2, 3 and durvalumab 1500 mg day 1 every 21 days × 4 cycles followed by maintenance durvalumab 1500 mg day 1 every 28 days (IA) Cisplatin 75–80 mg/m2 day 1 and etoposide 80–100 mg/m2 days 1, 2, 3 and durvalumab 1500 mg day 1 every 21 days × 4 cycles followed by maintenance durvalumab 1500 mg day 1 every 28 days (IA) Recommended regimens of chemotherapy (4–6 cycles) Preferred regimen Cisplatin 75 mg/m2 day 1 and etoposide 100 mg/m2 days 1–3, every 21 days (IA) Alternative regimens Carboplatin AUC 5–6 day 1 and etoposide 100 mg/m2 days 1–3, every 21 days (IA) Optional chemotherapy regimens (IIB) Carboplatin AUC 5 day 1 and irinotecan 50 mg/m 2 days 1, 8, 15 every 28 days Cisplatin 60 mg/m2 day 1 and irinotecan 60 mg/m2 days 1, 8, 15 every 28 days Cisplatin 30 mg/m2 days 1, 8 and irinotecan 65 mg/m2 days 1, 8 every 21 days Epirubicin 100 mg/m2 and cisplatin 100 mg/m2 on day 1 every 21 days |
Systemic regimens for second and successive lines | |
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Relapse ≤ 3 months Preferred regimen Clinical trial Topotecan oral or IV (I, B) Cyclophosphamide/doxorubicin/vincristine (CAV) (II, B) Other options (II, C) Nivolumab ± ipilimumab Pembrolizumab Paclitaxel Lurbinectedin Docetaxel Irinotecan Temozolomide Vinorelbine Gemcitabine Bendamustine Relapse > 3 months Reinduction with platinum–etoposide (II, B) |
Diagnosis, initial assessment and staging | Pathological diagnosis of SCLC should be made using the World Health Organization (WHO) classification Initial assessment must include medical/smoking histories, physical examination, complete blood count and biochemistry including liver enzymes, sodium, potassium, calcium, glucose, lactate dehydrogenase levels, and renal function test Lung function tests if thoracic radiation is indicated A computed tomography (CT) scan with intravenous contrast of the chest/abdomen is recommended Magnetic resonance imaging (MRI) (preferred) or CT scan (with intravenous contrast) for brain imaging 2-Fluor-2-desoxy-d-glucose positron-emission-tomography (FDG-PET CT) scan is recommended in localised disease. In patients with a solitary metastasis, its pathological confirmation is recommended (III, C) 8th edition of the TNM staging system according to the AJCC should be used (I, A). Combined use of TNM and VALSG classification is appropriate |
Treatment of limited stage I–IIA (T1–T2, N0, M0) | Lobectomy with a systematic lymph-node dissection is the preferred surgical procedure after mediastinal staging (II, A) Patients with N0 disease should be recommended adjuvant chemotherapy (II, A) Patients with pN1 or pN2 disease should be recommended adjuvant chemotherapy and thoracic radiotherapy (II, A) SBRT represents an alternative for patients with stage I–IIA SCLC with surgical contraindication or refusing surgery (III, B). After completion of SBRT patients should be receive 4 cycles of adjuvant chemotherapy (II, A) PCI is not recommended in T1–T2, N0, M0 patients |
Treatment of limited stage IIB–IIIC (T3–4 N0 M0; T1–4 N1–3, M0) | Patients should be treated with concurrent chemotherapy and thoracic radiotherapy (I, A) The recommended chemotherapy is the combination of 4 -6 cycles of cisplatin-etoposide (I, A). Carboplatin could replace cisplatin when contraindication (IA) 45 Gy with twice-daily fraction or 60–70 Gy with once-daily fraction are accepted treatments. Either of them should be administered concomitantly to systemic therapy (I, A) Radiotherapy should be started as early as with the 1st or 2nd course of chemotherapy (I, A) PCI (25 Gy) should be administered after CTRT in patients without progression (I, A) |
First-line treatment of extensive stage IV (T1–4 N1–3, M1 a,b,c) | The recommended first-line treatment is the use of platinum–etoposide + immunotherapy (I, A) Carboplatin–etoposide–atezolizumab 4 cycles followed by maintenance atezolizumab until progression Durvalumab–carboplatin or cisplatin + etoposide 4 cycles followed by maintenance with durvalumab until progression If no candidate to receive immunotherapy the recommended treatment is chemotherapy 4–6 cycles of cisplatin-etoposide. Carboplatin could replace cisplatin when contraindication (I, A) Alternative regimens are Cisplatin–irinotecan, carboplatin–irinotecan, cisplatin, and epirubicin (II, B) |
Radiotherapy in ES-SCLC | PCI (25 Gy) should be evaluated in patients with good PS who achieve a response (I, B). Depending of individual patient factors, close MRI surveillance should be appropriate in patients whose achieve a response to initial systemic therapy Consolidative thoracic radiation therapy should be considered in selected patients who have completed chemotherapy and achieved completed or near complete response (I, B) |
Second and successive lines treatment in SCLC | Patients who progress during treatment or less < 3 months, inclusion in clinical trial is highly recommended (II, C) Topotecan is recommended in resistant or sensitive relapse (I, B). Other alternative are VAC (II, B) Patients with sensitive relapse (3 months) reinduction treatment with platinum–etoposide is recommended (II, B) |
Fragile and elderly patients | Use same chemotherapy protocol than patients with PS 0–1 No immunotherapy in patients with PS 2–3 Consider dose attenuation or carboplatin-based regimens Consider the use of colony-stimulating factors (G-CSF) in PS 2–3 or age greater than or equal to 70 years In LS concurrent CTRT with modern technics could be a treatment option for fit and elderly patients In ES dose attenuation of cisplatin–etoposide or carboplatin–etoposide are adequate. Use of G-CSF recommended PCI (25 Gy) should be use with caution in elderly patients |
Follow-up | LS: CT scan every 3 months the first year, every 6 months year 2–3 and then annually (V, C) Extensive Stage every 2 months the first year, every 3 months years 2 and 3, every 6 months years 4–5 and then annually (V, C) |