Copyright ©The Author(s) 2021.
World J Clin Oncol. Mar 24, 2021; 12(3): 115-143
Published online Mar 24, 2021. doi: 10.5306/wjco.v12.i3.115
Table 1 Chronological changes in the combined treatment of small cell lung cancer
Chronological changes in SCLC treatment
Stage (LS or ES)
Median survival
5-yr survival
P value
Level of evidence
Miller et al[4] 1969LSIIIRT28.5 wk; 43 wk1%; 5%0.04A I
Bergsagel et al[8] 1972LSIIIRT; RT + Ch21 wk; 42 wkNR< 0.05A I
Einhorn et al[13] 1976LSIIRT + PCT12 mo10%C III
Bunn et al[18] 1987LSIIIPCT; PCT + RT12 mo; 15 mo10%; 15%< 0.05A I
Turrisi et al[27] 1988LSIIEarly AHF-RT + CE23 mo30% at 3 yrC III
Murray et al[26] 1993LSIIIEarly RT + CE; late RT + CE21 mo; 19 mo20%; 13%< 0.05A I
Pignon et al[21] 1992LSMeta-analysisPCT (no CE); PCT (no CE) + TRT< 14% mortality> 5% at 3 yr0.001A I
Jeremic et al[29] 1997LSIIIEarly AHF-RT + CE; late AHF-RT + CE36 mo; 34 mo30%; 15%0.0027A I
Turrisi et al[31] 1999LSIIIEarly AHF-RT + CE; early NFRT + CE23 mo; 19 mo26%; 16%0.04A I
Jeremic et al[41] 1999ESIIIPCT + RT + PCI; PCT + PCI17 mo; 11 mo9.1%; 3.7%0.0041A I
Aupérin et al[33] 1999LSMeta-analysisPCI; no PCI> 6% at 3 yrA I
Takada et al[30] 2002LSIIIEarly AHF-RT + CE; late AHF-RT + CE31.3 mo; 20.8 mo24%; 18%< 0.05A I
Slotman et al[38] 2007ESIIICE + PCI; CE27% at 1 yr; 13% at 1 yr< 0.001A I
Slotman et al[42] 2015ESIIICE + PCI; CE + TRT + PCI3% at 3 yr; 13% at 3 yr< 0.03A I
Faivre-Finn et al[43] 2017LSIIICE + AHF-RT 45 Gy; CE + NFRT 66 Gy29 mo; 19 mo34%; 31%NSA I
Table 2 Diagnostic staging recommendations for small cell lung cancer
Diagnosis of small cell lung carcinoma
Staging with combined VALSG and TNM AJCC 8th edition (I, A)
Baseline study
Age, tobacco use, comorbidities, complete physical examination, and ECOG PS
Complete blood analysis: Blood count, biochemistry, liver and kidney function, alkaline phosphatase, LDH
Cardiology study: Electrocardiogram +/- echocardiogram
Respiratory function testing in patients expected to receive locoregional treatment
CT with intravenous contrast (unless medically contraindicated)
Upper thoracoabdominal CT with intravenous contrast; include pelvis in advanced stages
Intravenous contrast improves the definition of central tumours and lymph node involvement (III, A)
18F-FDG PET/CT recommended in patients expected to undergo locoregional treatment (III, A)
Images are acquired with the patient in the radiotherapy treatment position according to consensus protocol between Nuclear Medicine and Radiation Oncology departments (IV, A)
Not recommended for restaging after chemotherapy in sequential treatment
Brain staging
Brain MRI is preferable
Brain CT with IV contrast (without contrast is inadequate)
Bone scintigraphy
Only indicated if PET/CT is not available
Abdominal MRI
Only indicated to assess uncertain liver or adrenal lesions (V, C)
Histological confirmation
Invasive tests used as appropriate according to tumour location
Follow WHO criteria for cell typing. Immunohistochemistry for differential diagnosis
Table 3 Tumor-node-metastasis American Joint Committee on Cancer 8th edition lung cancer
TNM AJCC 8th edition lung cancer
T: Primary tumour
TxNot evaluable by imaging or malignant cells in sputum or bronchial lavage
T0No evidence of primary tumour
TisCarcinoma in situ
T1≤ 3 cm surrounded by lung or visceral pleura, or lobar bronchus
T1a (mi)Minimally invasive
T1a≤ 1 cm
T1b> 1 cm to ≤ 2 cm
T1c> 2 cm to ≤ 3 cm
T2> 3 cm to ≤ 5 cm, or involving main bronchus without affecting the carina, visceral pleura, or atelectasis or obstructive pneumonitis extending to the hilar region, affecting part or all of the lung
T2a> 3 cm to ≤ 4 cm
T2b> 4 cm to ≤ 5 cm
T3> 5 cm to ≤ 7 cm, or tumour nodules in the same lobe, or invasion of the chest wall (parietal pleura), phrenic nerve, parietal pericardium
T4> 7 cm, or nodules in a different ipsilateral lobe or invasion of the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, and carina
N: Regional lymph node involvement
NxNot evaluable
N0No node involvement
N1Ipsilateral peribronchial and/or hilar and intrapulmonary nodes
N2Ipsilateral mediastinal nodes and/or subcarinal
N3Contralateral mediastinal or contralateral hilar nodes, or any scalene or supraclavicular nodes
M: Distant metastasis
M0No metastasis
M1Distant metastasis
M1aNodules in contralateral lobe; pleural or pericardial or pleural or pericardial effusion
M1bSingle extrathoracic metastasis (including non-regional lymph node)
M1cMultiple extrathoracic metastases
Table 4 Grouping by tumor-node-metastasis stage: American Joint Committee on Cancer 8th edition lung cancer
TNM AJCC 8th edition lung cancer grouping by stage
Occult carcinomaTxN0M0
Stage 0TisN0M0
Stage IA1T1a (mi)-T1aN0M0
Stage IA2T1bN0M0
Stage IA3T1cN0M0
Stage IBT2aN0M0
Stage IIAT2bN0M0
Stage IIBT1-2N1M0
Stage IIIAT1-2N2M0
Stage IIIBT1-2N3M0
Stage IIICT3-4N3M0
Stage IVAAny TAny NM1a-b
Stage IVBAny TAny NM1c
Table 5 Planning volumes in the principal studies of concurrent chemoradiotherapy in small cell lung cancer
Jeremic et al[41] 1999Prospective, randomisedGTV + hilum + 2 cm; entire mediastinum + both supraclavicular fossae + 1 cm
Zhu et al[116] 2011RetrospectivePrimary GTV + GTVn > 1 cm short axis
Yee et al[117] 2012Prospective, phase IIGTVp + GTVn visible on planning CT
Slotman et al[44] 2015Phase III, randomisedGTVp post-CT + 15 mm + ipsilateral hilum + nodes involved pre-CT
Luan et al[119] 2015RetrospectiveCR post-CT: Primary GTV bed and GTVn involved pre-CT; SD post-CT: GTVp + GTVn; PD post-CT: New GTVp + GTVn + GTV
Qin et al[118] 2016RetrospectiveGTV: Thoracic, mediastinal, and supraclavicular fossae
Gore et al[47] 2017Phase II, randomisedPost-CT volume including the primary tumour and nodal areas involved at diagnosis
Luo et al[120] 2017RetrospectivePost-CT GTVp + pre-CT primary tumour bed + GTVn of nodes involved pre-CT
Zhang et al[121] 2017Literature reviewCR: Mediastinum initially involved; PR: Residual pulmonary lesions + initially involved lymph nodes
Table 6 Summary of the main studies of prophylactic cranial irradiation in small cell lung cancer

Stage (LS or ES)
P value
Incidence of BM
P value
Level of evidence
Arriagada et al[144] 2002LSIIIPCI; no PCI18% at 5 yr; 15% at 5 yr0.0620% at 5 yr; 37% at 5 yr< 0.001A I
Aupérin et al[33] 1999LSMeta-analysisPCI; no PCI20.7%; 15.3%0.010.38; 0.570.001A I
Warde et al[20] 1992LSMeta-analysisPCI; no PCIHR 0.82HR 0.48A I
Takahashi et al[122] 2017ESIIIPCI; MRI + no PCI13.6 mo; 11.6 mo48%; 69%A I
Rusthoven et al[81] 2020IIIWBRT; SRS5.2 mo; 6.5 mo0.003A I
Yin et al[145] 2019Meta-analysisPCI; observationHR 0.81< 0.001HR 0.45< 0.001A II
De Ruysscher et al[146] 2018IIIPCI; observation24.2 mo; 21.9 mo0.567%; 27.2%0.001A I
Slotman et al[38] 2007ESIIIPCI; no PCI6.7 mo; 5.4 mo15% at 1 yr; 40% at 1 yr< 0.001A I
Le Péchoux et al[154] 2009LSIIIStandard dose PCI; high dose PCI42%; 37%0.0529% at 2 yr; 23% at 2 yr0.18A I
Ref.Stage (LS or ES)PhaseTreatmentMedian SurvivalP valueIncidence of neurological deficitP valueLevel of evidence
Yang et al[157] 2018LSMeta-analysisPCI; no PCIHR 0.52RR 0.5A I
Viani et al[148] 2012LS-ESMeta-analysisPCI; no PCIOR 0.730.01
Ge et al[149] 2018ESMeta-analysisPCI; no PCIHR 0.57< 0.001RR 0.47< 0.01A I
Brown et al[164] 2020IIIHA + WBRT + Memantine; WBRT + MemantineLearning 11.5%, memory 16.4%; learning 24.7%, memory 33.3%0.049; 0.02AI
van Meerbeeck et al[165] 2019IIIPCI; PCI + HAHVLT-R 28%; 29%> 0.05A I
De Dios et al[167] 2019LS-ESIIIPCI; PCI + HAFCSRT 21.7%, 32.6%, and 18.5% at 3, 6 and 12 mo; FCSRT 5.1%, 7.3% and 3.8% at 3, 6 and 12 mo< 0.05AI