The Journal of Practical Medicine >
Treatment strategies for limited⁃stage primary small cell carcinoma of esophagus
Received date: 2025-01-14
Online published: 2025-06-19
Primary small cell carcinoma of esophagus （PSCCE） is a rare and highly aggressive neuroendocrine tumor， accounting for 0.05% to 3.1% of all esophageal malignancies. Its biological characteristics are similar to those of small cell lung cancer， with highly aggressive behavior and early dissemination tendency. It often metastasizes rapidly through lymphatic and hematogenous pathways.The prognosis is extremely poor， with a 5-year overall survival rate of less than 15%. There are no large-scale randomized controlled trials， and no standard treatment strategies have been established. In recent years， the treatment of limited-stage PSCCE has become a focal point of research. In traditional treatment paradigms， endoscopic therapy is feasible for very early-stage cases， while radical surgery serves as the primary approach for relatively early-stage patients. For locally advanced cases， two predominant treatment modalities are commonly employed in clinical practice： a surgery-based comprehensive treatment regimen and a radical chemoradiotherapy-centered therapeutic protocol， with no definitive conclusion yet reached regarding the optimal treatment strategy. Concurrently， emerging therapeutic strategies such as immunotherapy and molecularly targeted therapy have demonstrated remarkable clinical efficacy， thereby providing novel therapeutic opportunities for limited-stage PSCCE. This article aims to review the recent advances in the treatment of limited-stage PSCCE， summarize the current diagnostic and therapeutic landscape， and outline future directions in this field.
Key words： small cell carcinoma; esophageal carcinoma; treatment; survival
Xiaolin QIU , Bingjie FAN , Linlin WANG . Treatment strategies for limited⁃stage primary small cell carcinoma of esophagus[J]. The Journal of Practical Medicine, 2025 , 41(11) : 1603 -1610 . DOI: 10.3969/j.issn.1006-5725.2025.11.001
| 1 | JEENE P M， GEIJSEN E D， MUIJS C T， et al. Small Cell Carcinoma of the Esophagus： A Nationwide Analysis of Treatment and Outcome at Patient Level in Locoregional Disease ［J］. Am J Clin Oncol， 2019， 42（6）： 534-538. doi:10.1097/coc.0000000000000546 |
| 2 | LIU D， WU D， NI J， et al. NSE and ProGRP Are Promising Markers for Diagnosis， Efficacy Evaluation， Follow-Up Monitoring， and Prognosis of Small Cell Esophageal Carcinoma ［J］. Thorac Cancer， 2025， 16（4）： e70026. doi:10.1111/1759-7714.70026 |
| 3 | ISHIDA H， KASAJIMA A， ONODERA Y， et al. A comparative analysis of clinicopathological factors between esophageal small cell and basaloid squamous cell carcinoma ［J］. Medicine （Baltimore）， 2019， 98（8）： e14363. doi:10.1097/md.0000000000014363 |
| 4 | PANDA G S， NORONHA V， YADAV S， et al. Small cell carcinoma of the oesophagus： Experience of an Indian Tertiary Cancer Centre ［J］. Ecancermedicalscience， 2022， 16：1393. doi:10.3332/ecancer.2022.1393 |
| 5 | LI T， CHEN S， ZHANG Z， et al. Chemotherapy Plus Radiotherapy Versus Radiotherapy in Patients With Small Cell Carcinoma of the Esophagus： A SEER Database Analysis ［J］. Cancer Control， 2021， 28：1073274821989321. doi:10.1177/1073274821989321 |
| 6 | AIJAZ P， NIAZI M A， CHELA H K， et al. Epigastric Pain and Dysphagia in a 36-Year-Old Man Due to Primary Esophageal Small Cell Carcinoma ［J］. Am J Case Rep， 2024， 25：e943392. doi:10.12659/ajcr.943392 |
| 7 | HOSSEINI S， SALEK R， NASROLAHI H， et al. Small Cell Carcinoma of the Esophagus： Clinicopathological Features and Outcome of 22 Cases ［J］. Iran Red Crescent Med J， 2015， 17（11）： e20353. doi:10.5812/ircmj.20353 |
| 8 | WALENKAMP A M， SONKE G S， SLEIJFER D T. Clinical and therapeutic aspects of extrapulmonary small cell carcinoma ［J］. Cancer Treat Rev， 2009， 35（3）： 228-236. doi:10.1016/j.ctrv.2008.10.007 |
| 9 | FRAZIER S R， KAPLAN P A， LOY T S. The pathology of extrapulmonary small cell carcinoma ［J］. Semin Oncol， 2007， 34（1）： 30-38. doi:10.1053/j.seminoncol.2006.11.017 |
| 10 | RICE T W， ISHWARAN H， FERGUSON M K， et al. Cancer of the Esophagus and Esophagogastric Junction： An Eighth Edition Staging Primer ［J］. J Thorac Oncol， 2017， 12（1）： 36-42. doi:10.1016/j.jtho.2016.10.016 |
| 11 | MIAO H， LI R， CHEN D， et al. Survival outcomes and prognostic factors of primary small cell carcinoma of the esophagus ［J］. J Thorac Dis， 2021， 13（5）： 2790-2802. doi:10.21037/jtd-20-3334 |
| 12 | WANG H H， ZAORSKY N G， MENG M B， et al. Multimodality therapy is recommended for limited-stage combined small cell esophageal carcinoma ［J］. Onco Targets Ther， 2015， 8：437-444. doi:10.2147/ott.s76048 |
| 13 | XIE M R， XU S B， SUN X H， et al. Role of surgery in the management and prognosis of limited-stage small cell carcinoma of the esophagus ［J］. Dis Esophagus， 2015， 28（5）： 476-482. doi:10.1111/dote.12230 |
| 14 | SONG Y， WANG W， TAO G， et al. Survival benefit of radiotherapy to patients with small cell esophagus carcinoma： an analysis of Surveillance Epidemiology and End Results （SEER） data ［J］. Oncotarget， 2016， 7（13）： 15474-15480. doi:10.18632/oncotarget.6764 |
| 15 | XU L， LI Y， LIU X， et al. Treatment Strategies and Prognostic Factors of Limited-Stage Primary Small Cell Carcinoma of the Esophagus ［J］. J Thorac Oncol， 2017， 12（12）： 1834-1844. doi:10.1016/j.jtho.2017.09.1966 |
| 16 | ZHAO K， HUANG Z， SI Y， et al. Use of Chemoradiotherapy as a Treatment Option for Patients with Limited-Stage Primary Small Cell Carcinoma of the Esophagus ［J］. Cancer Manag Res， 2021， 13：613-623. doi:10.2147/cmar.s278914 |
| 17 | ZHU J， WANG Y， SUN H， et al. Surgery versus radiotherapy for limited-stage small cell esophageal carcinoma： a multicenter， retrospective， cohort study in China （ChiSCEC） ［J］. Int J Surg， 2024， 110（2）： 956-964. doi:10.1097/JS9.0000000000000912 |
| 18 | ZEMERLY S， THURAIRAJASINGAM K， DEEB B， et al. Small Cell Oesophageal Carcinoma： A Retrospective Case Series From a UK Tertiary Centre and a Review of the Literature ［J］. Cureus， 2023， 15（11）： e49435. doi:10.7759/cureus.49435 |
| 19 | ZHU J， LIANG X， CHEN S， et al. Endoscopic therapy versus esophagectomy for T1bN0M0 esophageal cancer： A population-based study using propensity score matching ［J］. Heliyon， 2023， 9（11）： e22189. doi:10.1016/j.heliyon.2023.e22189 |
| 20 | YANG X， MEN Y， WANG J， et al. Additional Radiotherapy With or Without Chemotherapy Following Endoscopic Resection for Stage I Esophageal Carcinoma： A Pilot Study ［J］. Technol Cancer Res Treat， 2021， 20：15330338211048051. doi:10.1177/15330338211048051 |
| 21 | CHEN W W， WANG F， CHEN S， et al. Detailed analysis of prognostic factors in primary esophageal small cell carcinoma ［J］. Ann Thorac Surg， 2014， 97（6）： 1975-1981. doi:10.1016/j.athoracsur.2014.02.037 |
| 22 | ZOU B， LI T， ZHOU Q， et al. Adjuvant Therapeutic Modalities in Primary Small Cell Carcinoma of Esophagus Patients： A Retrospective Cohort Study of Multicenter Clinical Outcomes ［J］. Medicine （Baltimore）， 2016， 95（17）： e3507. doi:10.1097/md.0000000000003507 |
| 23 | FAN N， WANG Z， HUANG Y， et al. A Retrospective Study of 52 Patients With Primary Small Cell Carcinoma of the Esophagus Treated With Radical Surgery ［J］. Cancer Control， 2021， 28：10732748211027147. doi:10.1177/10732748211027147 |
| 24 | CAI G， WANG J， ZOU B， et al. Preoperative Chemotherapy for Limited-stage Small Cell Carcinoma of the Esophagus ［J］. Ann Thorac Surg， 2022， 114（4）： 1220-1228. doi:10.1016/j.athoracsur.2021.08.059 |
| 25 | YAN H， ZHU H， CAI Y， et al. Treatment strategies for limited-stage small cell carcinoma of the esophagus： Evidence from a Chinese multicenter cohort study and the American SEER database ［J］. J Thorac Dis， 2024， 16（11）： 7787-7796. doi:10.21037/jtd-24-1394 |
| 26 | WU J， XIA X， GONG L， et al. Neoadjuvant chemoimmunotherapy for small cell carcinoma of the esophagus： Clinical efficacy and biomarker exploration ［J］. Hum Vaccin Immunother， 2024， 20（1）： 2370085. doi:10.1080/21645515.2024.2370085 |
| 27 | QIN J， XUE L， HAO A， et al. Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma： The randomized phase 3 ESCORT-NEO/NCCES01 trial ［J］. Nat Med， 2024， 30（9）： 2549-2557. doi:10.1038/s41591-024-03064-w |
| 28 | LI C， ZHAO S， ZHENG Y， et al. Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma （PALACE-1） ［J］. Eur J Cancer， 2021， 144：232-241. doi:10.1016/j.ejca.2020.11.039 |
| 29 | LIU J， YANG Y， LIU Z， et al. Multicenter， single-arm， phase Ⅱ trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma ［J］. J Immunother Cancer， 2022， 10（3）： e004291. doi:10.1136/jitc-2021-004291corr1 |
| 30 | CHENG J， GUO M， YANG Y， et al. Perioperative Outcomes of Minimally Invasive Esophagectomy After Neoadjuvant Immunotherapy for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma ［J］. Front Immunol， 2022， 13：848881. doi:10.3389/fimmu.2022.848881 |
| 31 | XIAO Q， XIAO H， OUYANG S， et al. Primary small cell carcinoma of the esophagus： Comparison between a Chinese cohort and Surveillance， Epidemiology， and End Results （SEER） data ［J］. Cancer Med， 2019， 8（3）： 1074-1085. doi:10.1002/cam4.2001 |
| 32 | JEENE P M， GEIJSEN E D， MUIJS C T， et al. Small Cell Carcinoma of the Esophagus： A Nationwide Analysis of Treatment and Outcome at Patient Level in Locoregional Disease ［J］. Am J Clin Oncol， 2019， 42（6）： 534-538. doi:10.1097/coc.0000000000000546 |
| 33 | LI R， YANG Z， SHAO F， et al. Multi-omics profiling of primary small cell carcinoma of the esophagus reveals RB1 disruption and additional molecular subtypes ［J］. Nat Commun， 2021， 12（1）： 3785. doi:10.1038/s41467-021-24043-6 |
| 34 | VERMA V， SLEIGHTHOLM R L， FANG P， et al. National Cancer Database report of nonmetastatic esophageal small cell carcinoma ［J］. Cancer Med， 2018， 7（12）： 6365-6373. doi:10.1002/cam4.1712 |
| 35 | WONG A T， SHAO M， RINEER J， et al. Treatment and survival outcomes of small cell carcinoma of the esophagus： an analysis of the National Cancer Data Base ［J］. Dis Esophagus， 2017， 30（2）： 1-5. |
| 36 | MENG M B， ZAORSKY N G， JIANG C， et al. Radiotherapy and chemotherapy are associated with improved outcomes over surgery and chemotherapy in the management of limited-stage small cell esophageal carcinoma ［J］. Radiother Oncol， 2013， 106（3）： 317-322. doi:10.1016/j.radonc.2013.01.008 |
| 37 | DING J， JI J， ZHU W， et al. A retrospective study of different treatments of limited-stage small-cell esophageal carcinoma and associated prognostic factor analysis ［J］. Dis Esophagus， 2013， 26（7）： 696-702. doi:10.1111/dote.12017 |
| 38 | GAO R， ZHANG Y， WEN X P， et al. Chemotherapy with cisplatin or carboplatin in combination with etoposide for small-cell esophageal cancer： a systemic analysis of case series ［J］. Dis Esophagus， 2014， 27（8）： 764-769. doi:10.1111/dote.12149 |
| 39 | 郝雁冰， 王丽， 容宇， 等. 3种化疗方案用于小细胞食管癌的疗效和安全性比较 ［J］. 中国药房， 2017， 28（12）： 1623-1625. doi:10.6039/j.issn.1001-0408.2017.12.12 |
| 40 | SHAPIRO J， VAN LANSCHOT J J B， HULSHOF M， et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer （CROSS）： long-term results of a randomised controlled trial ［J］. Lancet Oncol， 2015， 16（9）： 1090-1098. doi:10.1016/S1470-2045(15)00040-6 |
| 41 | YAN X， DUAN H， NI Y， et al. Tislelizumab combined with chemotherapy as neoadjuvant therapy for surgically resectable esophageal cancer： A prospective， single-arm， phase II study （TD-NICE） ［J］. Int J Surg， 2022， 103：106680. doi:10.1097/js9.0000000000000292 |
| 42 | HERMANN R M， CHRISTIANSEN H. A new standard is emerging： PD-1 maintenance therapy after neoadjuvant radiochemotherapy and curative resection of oesophageal and AEG carcinomas （CheckMate 577） ［J］. Strahlenther Onkol， 2021， 197（11）： 1040-1042. doi:10.1007/s00066-021-01849-3 |
| 43 | ZHAO Q， CHEN Y X， WU Q N， et al. Systematic analysis of the transcriptome in small-cell carcinoma of the oesophagus reveals its immune microenvironment ［J］. Clin Transl Immunology， 2020， 9（10）： e1173. doi:10.1002/cti2.1173 |
| 44 | ZHAO K， MA L， FENG L， et al. CD155 Overexpression Correlates With Poor Prognosis in Primary Small Cell Carcinoma of the Esophagus ［J］. Front Mol Biosci， 2020， 7：608404. doi:10.3389/fmolb.2020.608404 |
| 45 | YAMASHITA S， ABE H， YAMASHITA H， et al. PD-L1 and HLA-class I expression status and their therapeutic implication in oesophageal small-cell carcinoma ［J］. Histopathol， 2023， 83（2）： 264-275. doi:10.1111/his.14924 |
| 46 | ZHANG C， ZHANG G， XUE L， et al. Patterns and prognostic values of programmed cell death-ligand 1 expression and CD8 + T-cell infiltration in small cell carcinoma of the esophagus： a retrospective analysis of 34 years of National Cancer Center data in China ［J］. Int J Surg， 2024， 110（7）： 4297-4309. doi:10.1097/js9.0000000000000064 |
| 47 | SENAN S， OKAMOTO I， LEE G W， et al. Design and Rationale for a Phase Ⅲ， Randomized， Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer： The ADRIATIC Study ［J］. Clin Lung Cancer， 2020， 21（2）： e84-e88. doi:10.1016/j.cllc.2019.12.006 |
| 48 | SHAH M A， BENNOUNA J， DOI T， et al. KEYNOTE-975 study design： a Phase Ⅲ study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma ［J］. Future Oncol， 2021， 17（10）： 1143-1153. doi:10.2217/fon-2020-0969 |
| 49 | SUN J， GAN W， YAO J， et al. Peripheral blood lymphocyte subpopulations as predictive biomarkers for first-line programmed death 1 inhibitors efficacy in esophageal squamous cell carcinoma： A retrospective study ［J］. Medicine （Baltimore）， 2024， 103（40）： e39967. doi:10.1097/MD.0000000000039967 |
| 50 | CHEN W， CAO K， ZHANG L， et al. Efficacy and safety evaluation of frontline immunotherapy combinations in advanced esophageal squamous cell carcinoma： A network meta-analysis highlighting the value of PD-L1 expression positivity scores ［J］. Front Immunol， 2024， 15：1414753. doi:10.3389/fimmu.2024.1414753 |
| 51 | 王豪， 陆筱祎， 王文杰. 老年局部晚期食管癌同步放化疗序贯信迪利单抗免疫治疗的疗效 ［J］. 实用医学杂志， 2025， 41（3）： 365-370. |
| 52 | REN W， WU P， TIAN J， et al. Anti-PD-1 therapy plus chemotherapy showed superior and durable survival benefit in a patient with small cell esophageal cancer： A case report ［J］. Thorac Cancer， 2021， 12（2）： 264-267. doi:10.1111/1759-7714.13735 |
| 53 | ISHIDA H， KASAJIMA A， KAMEI T， et al. SOX2 and Rb1 in esophageal small-cell carcinoma： Their possible involvement in pathogenesis ［J］. Mod Pathol， 2017， 30（5）： 660-671. doi:10.1038/modpathol.2016.222 |
| 54 | WANG F， LIU D B， ZHAO Q， et al. The genomic landscape of small cell carcinoma of the esophagus ［J］. Cell Res， 2018， 28（7）： 771-774. doi:10.1038/s41422-018-0039-1 |
| 55 | ZHU M， CHU Y， YUAN Q， et al. Integrated bioinformatics analysis to explore potential therapeutic targets and drugs for small cell carcinoma of the esophagus ［J］. Front Bioinform， 2025， 5：1495052. doi:10.3389/fbinf.2025.1495052 |
| 56 | 周乾华， 毕华俊， 孟凡东， 等. miR-30b-5p通过下调MKRN3表达抑制食管癌细胞增殖、迁移和侵袭 ［J］. 实用医学杂志， 2023， 39（13）： 1627-1633. |
| 57 | ZHANG C， YU G M， ZHANG M， et al. S-1 plus apatinib followed by salvage esophagectomy for irinotecan-refractory small cell carcinoma of the esophagus： A case report and review of the literature ［J］. Medicine （Baltimore）， 2020， 99（3）： e18892. doi:10.1097/md.0000000000018691 |
| 58 | WANG W， ZHANG X， FANG Y， et al. Case Report： Olaparib Shows Satisfactory Clinical Outcomes Against Small Cell Esophageal Carcinoma With ATM Mutation ［J］. Front Oncol， 2022， 12：808801. doi:10.3389/fonc.2022.808801 |
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