{"entity":{"id":"limited-stage-sclc","kind":"cancer","name":"Limited-stage small-cell lung cancer","aka":["LS-SCLC","Limited-disease small-cell lung cancer","Stage I to III small-cell lung cancer"],"tldr":"Small-cell lung cancer that is still confined to one side of the chest is treated to cure with chemotherapy and radiotherapy given together. Adding two years of the immunotherapy antibody durvalumab afterwards lengthened median survival from under three years to over four and a half, the first improvement in this disease in decades.","summary":"Small-cell lung cancer grows fast, spreads early and responds dramatically but briefly to chemotherapy. Limited-stage disease, defined since the 1950s as disease encompassable in one radiation field, is treated with four cycles of cisplatin or carboplatin plus etoposide and concurrent thoracic radiotherapy started with the first or second cycle. Turrisi's trial (1999) showed that 45 Gy in twice-daily fractions over three weeks improved five-year survival from 16 to 26 percent compared with the same dose once daily, and CONVERT (2017) found that 66 Gy once daily was not better than the twice-daily schedule, so both are accepted. Prophylactic cranial irradiation for patients in response cut brain relapse and improved three-year survival from 15 to 21 percent in the 1999 Aupérin meta-analysis, though MRI surveillance is being tested as an alternative because of its effect on memory.\n\nFor twenty-five years nothing improved on this until ADRIATIC (2024): 730 patients without progression after chemoradiation were randomised to durvalumab for up to two years, placebo, or durvalumab plus tremelimumab. Durvalumab alone lengthened median overall survival from 33.4 to 55.9 months (hazard ratio 0.73) and progression-free survival from 9.2 to 16.6 months, with pneumonitis of any grade in about a third of patients in both arms. The FDA approved durvalumab consolidation in December 2024 and it has become the standard.\n\nThe next steps are testing the DLL3 T-cell engager tarlatamab after chemoradiation (DeLLphi-306) and checkpoint inhibitors given during rather than after chemoradiation; surgery is limited to the rare stage I tumour found incidentally. Open questions are whether prophylactic cranial irradiation is still needed with modern MRI surveillance, the best radiotherapy dose and schedule with immunotherapy, and how to treat the majority who still relapse.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Small-cell_carcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Small-cell_carcinoma"},{"label":"NCCN Guidelines: Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1462"}],"tags":["subtype-page","lung"],"related":[],"cancers":[],"sections":[],"technologies":["imrt-igrt","checkpoint-inhibitor","prophylactic-cranial-irradiation","cytotoxic-chemotherapy","platinum","pet-ct","mri","t-cell-engager"],"targets":["pdl1","dll3","tp53"],"drugs":["durvalumab","platinum-etoposide","cisplatin","carboplatin","etoposide","tremelimumab","tarlatamab","lurbinectedin","topotecan"],"companies":["astrazeneca","amgen"],"institutions":[],"pathways":["sclc-signalling","p53-cell-cycle","pd1-checkpoint"],"terms":["limited-extensive-stage","chemoradiation","pci-term","consolidation-therapy","radiation-pneumonitis","histologic-transformation"],"trials":["adriatic","convert","nct06117774","dellphi-304"],"people":["cheng-ying","fiona-blackhall","charles-rudin","luis-paz-ares"],"bottlenecks":[],"keyPapers":["paper-adriatic-nejm-2024"],"journals":[],"dependsOn":[],"notes":[],"group":"lung","burden":"About 30 percent of small-cell lung cancers are limited stage, confined to one side of the chest and its regional nodes so that they fit in a single radiotherapy field; almost all patients are current or former heavy smokers. Median survival was 25 to 30 months with chemoradiation and about a fifth to a quarter were cured.","subtypes":["Limited-stage small-cell lung cancer, stage I to III, fit for concurrent chemoradiation (durvalumab consolidation)","Very limited stage I small-cell lung cancer (surgery then chemotherapy)","Limited-stage small-cell disease unfit for concurrent treatment (sequential chemoradiation)","Small-cell lung cancer transformed from EGFR-mutated adenocarcinoma"],"biomarkers":["Stage by PET-CT and brain MRI (limited versus extensive is the main decision)","Response after chemoradiation (eligibility for durvalumab)","Pulmonary function and radiation dose constraints","Neuroendocrine markers on pathology (synaptophysin, chromogranin, INSM1)","Transcription factor subtype (ASCL1, NEUROD1, POU2F3; research)"],"standardOfCare":[{"setting":"Limited stage, fit","approach":"Four cycles of cisplatin or carboplatin plus etoposide with concurrent thoracic radiotherapy (45 Gy twice daily or 60 to 66 Gy once daily) started by cycle two, then durvalumab for up to two years in patients without progression (ADRIATIC).","refs":["platinum-etoposide","cisplatin","carboplatin","etoposide","imrt-igrt","chemoradiation","convert","durvalumab","adriatic","consolidation-therapy"],"guideline":{"version":"NCCN Guidelines: Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1462"}},{"setting":"After response: brain","approach":"Prophylactic cranial irradiation (25 Gy in 10 fractions) or MRI surveillance every three months in patients who decline it or are older; hippocampal avoidance where available.","refs":["prophylactic-cranial-irradiation","pci-term","mri","idea-mri-surveillance-replaces-pci"],"guideline":{"version":"NCCN Guidelines: Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1462"}},{"setting":"Stage I, node-negative, found incidentally","approach":"Lobectomy with node dissection then four cycles of platinum-etoposide; radiotherapy if nodes are positive.","refs":["lobectomy","platinum-etoposide"],"guideline":{"version":"NCCN Guidelines: Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1462"}},{"setting":"Relapse","approach":"As for extensive-stage disease: tarlatamab, lurbinectedin or topotecan, or rechallenge with platinum-etoposide if relapse is late.","refs":["tarlatamab","dellphi-304","lurbinectedin","topotecan","platinum-etoposide"],"guideline":{"version":"NCCN Guidelines: Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1462"}}],"stateOfArt":["Durvalumab consolidation after chemoradiation (ADRIATIC): median survival 55.9 versus 33.4 months.","Twice-daily 45 Gy or once-daily 60 to 66 Gy thoracic radiotherapy, both accepted (CONVERT).","MRI surveillance under test as an alternative to prophylactic cranial irradiation.","Tarlatamab after chemoradiation in phase 3 (DeLLphi-306)."],"history":[{"year":1957,"title":"Veterans Administration Lung Study Group defines limited and extensive stage","refs":["limited-extensive-stage"]},{"year":1992,"title":"Meta-analysis: adding thoracic radiotherapy to chemotherapy improves survival in limited stage","refs":["chemoradiation","imrt-igrt"]},{"year":1999,"title":"Turrisi: twice-daily 45 Gy improves five-year survival to 26 percent; Aupérin meta-analysis: prophylactic cranial irradiation improves survival","refs":["prophylactic-cranial-irradiation","platinum-etoposide"]},{"year":2017,"title":"CONVERT: 66 Gy once daily not superior to 45 Gy twice daily","refs":["convert","fiona-blackhall"]},{"year":2024,"title":"ADRIATIC: durvalumab after chemoradiation lengthens survival by almost two years; FDA approval","refs":["adriatic","durvalumab","cheng-ying","paper-adriatic-nejm-2024"]}],"pipeline":["nct06117774","tarlatamab","idea-mri-surveillance-replaces-pci","idea-sclc-subtype-directed","t-cell-engager"],"openProblems":["Whether prophylactic cranial irradiation still helps when MRI surveillance is available is being tested in randomised trials.","The best radiotherapy dose and schedule to combine with immunotherapy is unknown.","Most patients still relapse after chemoradiation and durvalumab, and there is no biomarker for who will be cured.","Transformed small-cell disease arising from EGFR-mutated adenocarcinoma is treated as limited or extensive stage without evidence specific to it."],"parent":"sclc"},"route":"/cancers/limited-stage-sclc/","neighbours":{"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"},{"id":"prophylactic-cranial-irradiation","kind":"technology","name":"Prophylactic cranial irradiation vs MRI surveillance","route":"/technologies/prophylactic-cranial-irradiation/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"target":[{"id":"dll3","kind":"target","name":"DLL3","route":"/targets/dll3/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"lurbinectedin","kind":"drug","name":"Lurbinectedin","route":"/drugs/lurbinectedin/"},{"id":"platinum-etoposide","kind":"drug","name":"Platinum + etoposide (EP / CE)","route":"/drugs/platinum-etoposide/"},{"id":"tarlatamab","kind":"drug","name":"Tarlatamab","route":"/drugs/tarlatamab/"},{"id":"topotecan","kind":"drug","name":"Topotecan","route":"/drugs/topotecan/"},{"id":"tremelimumab","kind":"drug","name":"Tremelimumab","route":"/drugs/tremelimumab/"}],"company":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"},{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"pathway":[{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"},{"id":"sclc-signalling","kind":"pathway","name":"Small cell lung cancer (KEGG map)","route":"/pathways/sclc-signalling/"}],"term":[{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"},{"id":"consolidation-therapy","kind":"term","name":"Consolidation therapy","route":"/terms/consolidation-therapy/"},{"id":"histologic-transformation","kind":"term","name":"Histologic transformation","route":"/terms/histologic-transformation/"},{"id":"limited-extensive-stage","kind":"term","name":"Limited-stage vs extensive-stage (small-cell lung cancer)","route":"/terms/limited-extensive-stage/"},{"id":"lobectomy","kind":"term","name":"Lobectomy","route":"/terms/lobectomy/"},{"id":"pci-term","kind":"term","name":"Prophylactic cranial irradiation (PCI)","route":"/terms/pci-term/"},{"id":"radiation-pneumonitis","kind":"term","name":"Radiation pneumonitis and lung fibrosis","route":"/terms/radiation-pneumonitis/"}],"trial":[{"id":"adriatic","kind":"trial","name":"ADRIATIC","route":"/trials/adriatic/"},{"id":"convert","kind":"trial","name":"CONVERT","route":"/trials/convert/"},{"id":"dellphi-304","kind":"trial","name":"DeLLphi-304","route":"/trials/dellphi-304/"},{"id":"nct06117774","kind":"trial","name":"Study Evaluating Tarlatamab After Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer (LS-SCLC)","route":"/trials/nct06117774/"}],"person":[{"id":"charles-rudin","kind":"person","name":"Charles M. Rudin","route":"/people/charles-rudin/"},{"id":"fiona-blackhall","kind":"person","name":"Fiona Blackhall","route":"/people/fiona-blackhall/"},{"id":"luis-paz-ares","kind":"person","name":"Luis Paz-Ares","route":"/people/luis-paz-ares/"},{"id":"cheng-ying","kind":"person","name":"Ying Cheng","route":"/people/cheng-ying/"}],"paper":[{"id":"paper-adriatic-nejm-2024","kind":"paper","name":"ADRIATIC: durvalumab after chemoradiotherapy for limited-stage small-cell lung cancer","route":"/key-papers/paper-adriatic-nejm-2024/"}],"idea":[{"id":"idea-mri-surveillance-replaces-pci","kind":"idea","name":"MRI surveillance replaces prophylactic cranial irradiation in SCLC","route":"/ideas/idea-mri-surveillance-replaces-pci/"},{"id":"idea-sclc-subtype-directed","kind":"idea","name":"Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)","route":"/ideas/idea-sclc-subtype-directed/"}],"cancer":[{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}]}}