胸段食管鳞状细胞癌术后复发转移模式研究进展

doi:10.3760/cma.j.cn371439-20251119-00088

摘要/Abstract

摘要：

胸段食管鳞状细胞癌（ESCC）术后复发转移是影响患者预后的关键因素。术后复发转移模式受肿瘤解剖位置、病理特征、生物学行为、对新辅助治疗的病理反应、治疗方式等多因素共同影响。随着新辅助治疗模式的演进，术后复发转移模式正经历从单纯手术的“局部复发主导型”，到新辅助放化疗的“远处转移主导型”，再到因免疫治疗的引入而可能实现的“局部-全身平衡控制型”。术后复发转移模式的演变深刻反映了不同治疗策略的作用机制与局限。系统了解胸段ESCC术后复发转移模式及其影响因素，并深入分析不同治疗策略背后的生物学机制是优化围手术期治疗策略、改善患者预后的关键所在。

关键词: 食道鳞癌, 复发, 肿瘤转移, 免疫疗法, 肿瘤微环境

Abstract:

Postoperative recurrence and metastasis of thoracic esophageal squamous cell carcinoma （ESCC） are key factors affecting patient prognosis. Patterns of postoperative recurrence and metastasis are jointly influenced by multiple factors，including the anatomical location of the tumor，pathological characteristics，biological behavior，pathological response to neoadjuvant therapy，and treatment modalities. With the evolution of neoadjuvant treatment strategies，patterns of postoperative recurrence and metastasis have shifted from a "locoregional recurrence-dominant" pattern of surgery alone，to a "distant metastasis-dominant" pattern of neoadjuvant chemoradiotherapy，and further to a potentially "local-systemic balanced control" pattern with the introduction of immunotherapy. The evolution of postoperative recurrence and metastasis patterns profoundly reflects the mechanisms and limitations of different treatment strategies. A systematic understanding of postoperative recurrence and metastasis patterns in thoracic ESCC，as well as the influencing factors，and conducting an in-depth analysis of the biological mechanisms underlying different treatment strategies，is crucial for optimizing perioperative treatment strategies and improving patient prognosis.

Key words: Esophageal squamous cell carcinoma, Recurrence, Neoplasm metastasis, Immunotherapy, Tumor microenvironment

毕士祥, 尹贻波, 刘文健. 胸段食管鳞状细胞癌术后复发转移模式研究进展[J]. 国际肿瘤学杂志, 2026, 53(9): 554-558.

Bi Shixiang, Yin Yibo, Liu Wenjian. Research progress on postoperative recurrence and metastasis patterns of thoracic esophageal squamous cell carcinoma[J]. Journal of International Oncology, 2026, 53(9): 554-558.

参考文献 40

[1]	Emi M, Hamai Y, Yoshikawa T, et al. Postoperative lymph node recurrence in esophageal cancer after surgery and prognosis of chemoradiotherapy[J]. Cancer Diagn Progn, 2024, 4(3): 276-280. DOI: 10.21873/cdp.10320.
[2]	Hanahan D. Hallmarks of cancer: new dimensions[J]. Cancer Discov, 2022, 12(1): 31-46. DOI: 10.1158/2159-8290.CD-21-1059.
[3]	Cui TT, Zhang HJ, Yu T, et al. Pattern of recurrence in 428 patients with thoracic esophageal squamous cell carcinoma after radical surgery and its implication in postoperative radiotherapeutic clinical target volume[J]. Front Oncol, 2021, 11: 652365. DOI: 10.3389/fonc.2021.652365.
[4]	Ni WJ, Yang JS, Deng W, et al. Patterns of recurrence after surgery and efficacy of salvage therapy after recurrence in patients with thoracic esophageal squamous cell carcinoma[J]. BMC Cancer, 2020, 20(1): 144. DOI: 10.1186/s12885-020-6622-0.
[5]	Zhao Q, Sun JL, Zheng F, et al. Accurate location describe and management of lymph node recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma: a retrospective cohort study[J]. Int J Surg, 2024, 110(6): 3440-3449. DOI: 10.1097/JS9.0000000000001242.
[6]	Wang YC, Zhu LY, Xia WL, et al. Anatomy of lymphatic drainage of the esophagus and lymph node metastasis of thoracic esophageal cancer[J]. Cancer Manag Res, 2018, 10: 6295-6303. DOI: 10.2147/CMAR.S182436.
[7]	Du RX, Fan SQ, Yang D, et al. Exploration of lymph node recurrence patterns and delineation guidelines of radiation field in middle thoracic oesophageal carcinomas after radical surgery: a real-world study[J]. BMC Cancer, 2024, 24(1): 596. DOI: 10.1186/s12885-024-12297-4.
[8]	Zhou JF, Yang YS, Zhang HL, et al. Lymphovascular and perineural invasion after neoadjuvant therapy in esophageal squamous carcinoma[J]. Ann Thorac Surg, 2023, 115(6): 1386-1394. DOI: 10.1016/j.athoracsur.2022.07.052.
[9]	Li MH, Zhang ZC, Wang QR, et al. Integrated cohort of esophageal squamous cell cancer reveals genomic features underlying clinical characteristics[J]. Nat Commun, 2022, 13(1): 5268. DOI: 10.1038/s41467-022-32962-1.
[10]	刁勇, 李智慧, 李小凯, 等. 胸段食管鳞癌术后复发模式及术后放疗靶区的研究[J]. 现代肿瘤医学, 2022, 30(13): 2420-2424. DOI: 10.3969/j.issn.1672-4992.2022.13.025.
[11]	Lo SM, Wu TS, Hsiao TH, et al. Single-cell transcriptomic analysis reveals distinct cancer-associated fibroblast signatures in treatment-refractory esophageal squamous cell carcinoma[J]. Sci Rep, 2025, 16(1): 169. DOI: 10.1038/s41598-025-28903-9.
[12]	Azad TD, Chaudhuri AA, Fang P, et al. Circulating tumor DNA analysis for detection of minimal residual disease after chemoradiotherapy for localized esophageal cancer[J]. Gastroenterology, 2020, 158(3): 494-505.e6. DOI: 10.1053/j.gastro.2019.10.039.
[13]	Eyck BM, van Lanschot JJB, Hulshof MCCM, et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: the randomized controlled CROSS trial[J]. J Clin Oncol, 2021, 39(18): 1995-2004. DOI: 10.1200/JCO.20.03614.
[14]	Liu S, Wen J, Yang H, et al. Recurrence patterns after neoadjuvant chemoradiotherapy compared with surgery alone in oesophageal squamous cell carcinoma: results from the multicenter phase Ⅲ trial NEOCRTEC5010[J]. Eur J Cancer, 2020, 138: 113-121. DOI: 10.1016/j.ejca.2020.08.002.
[15]	Wang MY, Wang S, Desai J, et al. Therapeutic strategies to remodel immunologically cold tumors[J]. Clin Transl Immunology, 2020, 9(12): e1226. DOI: 10.1002/cti2.1226.
[16]	Jiao YF, Cao FY, Liu H. Radiation-induced cell death and its mechanisms[J]. Health Phys, 2022, 123(5): 376-386. DOI: 10.1097/HP.0000000000001601.
[17]	Liu C, Li XH, Huang QY, et al. Single-cell RNA-sequencing reveals radiochemotherapy-induced innate immune activation and MHC-Ⅱ upregulation in cervical cancer[J]. Signal Transduct Target Ther, 2023, 8(1): 44. DOI: 10.1038/s41392-022-01264-9.
[18]	Zhai D, An DD, Wan C, et al. Radiotherapy: brightness and dark-ness in the era of immunotherapy[J]. Transl Oncol, 2022, 19: 101366. DOI: 10.1016/j.tranon.2022.101366.
[19]	Kato K, Machida R, Ito Y, et al. Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): a randomised, controlled, open-label, phase 3 trial[J]. Lancet, 2024, 404(10447): 55-66. DOI: 10.1016/S0140-6736(24)00745-1.
[20]	Qin JJ, Xue LY, 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.
[21]	Guo XF, Chen CJ, Zhao JB, et al. Neoadjuvant chemoradiotherapy vs chemoimmunotherapy for esophageal squamous cell carcinoma[J]. JAMA Surg, 2025, 160(5): 565-574. DOI: 10.1001/jamasurg.2025.0220.
[22]	Jing SW, Zhai C, Zhang W, et al. Comparison of neoadjuvant immunotherapy plus chemotherapy versus chemotherapy alone for patients with locally advanced esophageal squamous cell carcinoma: a propensity score matching[J]. Front Immunol, 2022, 13: 970534. DOI: 10.3389/fimmu.2022.970534.
[23]	Liu ZC, Zhang YR, Ma N, et al. Progenitor-like exhausted SPRY1⁺ CD8⁺ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma[J]. Cancer Cell, 2023, 41(11): 1852-1870.e9. DOI: 10.1016/j.ccell.2023.09.011.
[24]	Yin J, Yuan JN, Li YJ, et al. Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial[J]. Nat Med, 2023, 29(8): 2068-2078. DOI: 10.1038/s41591-023-02469-3.
[25]	Gubin MM, Vesely MD. Cancer immunoediting in the era of immuno-oncology[J]. Clin Cancer Res, 2022, 28(18): 3917-3928. DOI: 10.1158/1078-0432.CCR-21-1804.
[26]	Patin EC, Dillon MT, Nenclares P, et al. Harnessing radiotherapy-induced NK-cell activity by combining DNA damage-response inhibition and immune checkpoint blockade[J]. J Immunother Cancer, 2022, 10(3): e004306. DOI: 10.1136/jitc-2021-004306.
[27]	Sharon S, Daher-Ghanem N, Zaid D, et al. The immunogenic radiation and new players in immunotherapy and targeted therapy for head and neck cancer[J]. Front Oral Health, 2023, 4: 1180869. DOI: 10.3389/froh.2023.1180869.
[28]	van den Ende T, de Clercq NC, van Berge Henegouwen MI, et al. Neoadjuvant chemoradiotherapy combined with atezolizumab for resectable esophageal adenocarcinoma: a single-arm phase Ⅱ feasibility trial (PERFECT)[J]. Clin Cancer Res, 2021, 27(12): 3351-3359. DOI: 10.1158/1078-0432.CCR-20-4443.
[29]	Li CQ, Zhao SG, Zheng YY, 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.
[30]	Liu FJ, Wang DQ, Rong YM, et al. Safety and efficacy of neoadjuvant toripalimab plus chemotherapy followed by chemoradiotherapy for locally advanced esophageal squamous cell carcinoma in China (GASTO 1071): a non-randomised, two-cohort, phase 2 trial[J]. EClinicalMedicine, 2025, 82: 103184. DOI: 10.1016/j.eclinm.2025.103184.
[31]	梁秀, 李杰. 免疫治疗时代食管癌的放疗价值[J]. 中国癌症防治杂志, 2023, 15(6): 690-695. DOI: 10.3969/j.issn.1674-5671.2023.06.16.
[32]	Zhang ZF, Liu X, Chen DW, et al. Radiotherapy combined with immunotherapy: the dawn of cancer treatment[J]. Signal Transduct Target Ther, 2022, 7(1): 258. DOI: 10.1038/s41392-022-01102-y.
[33]	伊艳, 李宝生. 食管癌个体化精准综合治疗进展[J]. 国际肿瘤学杂志, 2025, 52(5): 257-261. DOI: 10.3760/cma.j.cn371439-20250415-00044.
[34]	Wu YY, Dai L, Yang YB, et al. Long-term survival and recurrence patterns in locally advanced esophageal squamous cell carcinoma patients with pathologic complete response after neoadjuvant chemotherapy followed by surgery[J]. Ann Surg Oncol, 2024, 31(8): 5047-5054. DOI: 10.1245/s10434-023-14809-1.
[35]	Wang ZF, Meng YC, Zhang F, et al. Tumor immune microenvironment analysis in different pathologic responses to neoadjuvant immunotherapy combined with chemotherapy in non-small cell lung cancer[J]. Transl Lung Cancer Res, 2025, 14(9): 3975-3987. DOI: 10.21037/tlcr-2025-17.
[36]	Jiang J, Xu C, Han DH, et al. Functional heterogeneity of cancer-associated fibroblasts with distinct neoadjuvant immunotherapy plus chemotherapy response in esophageal squamous cell carcinoma[J]. Biomark Res, 2024, 12(1): 113. DOI: 10.1186/s40364-024-00656-z.
[37]	中国临床肿瘤学会. 中国临床肿瘤学会食管癌诊疗指南(2025)[M]. 北京: 人民卫生出版社, 2025.
[38]	Wu L, Li BS, Wan G, et al. Toripalimab plus chemotherapy and radiotherapy for treatment-naive advanced esophageal squamous cell carcinoma: a single-arm phase 2 trial[J]. Nat Commun, 2024, 15(1): 7116. DOI: 10.1038/s41467-024-51105-2.
[39]	Koga N, Morita M, Nagai T, et al. Multimodal therapy for oligometastases after curative esophagectomy for esophageal cancer[J]. Esophagus, 2025, 22(3): 418-426. DOI: 10.1007/s10388-025-01125-8.
[40]	Liu Q, Chen JQ, Lin Y, et al. Systemic therapy with or without local intervention for oligometastatic oesophageal squamous cell carcinoma (ESO-Shanghai 13): an open-label, randomised, phase 2 trial[J]. Lancet Gastroenterol Hepatol, 2024, 9(1): 45-55. DOI: 10.1016/S2468-1253(23)00316-3.