Radiotherapy for Anastomotic Recurrence and Regional Lymph Node Metastases after Esophagectomy for Esophageal Cancer: Current Evidence and Open Questions

Yinghai Han

doi:10.62177/apjcmr.v2i5.1752

Authors

Yinghai Han Ningbo University

DOI:

https://doi.org/10.62177/apjcmr.v2i5.1752

Keywords:

Esophageal Cancer, Esophagectomy, Anastomotic Recurrence, Lymph Node Metastasis, Radiotherapy, Re-Irradiation

Abstract

Surgery remains the mainstay of curative treatment for localized esophageal cancer, yet a substantial proportion of patients relapse after esophagectomy, most often at the anastomosis or in the regional lymph nodes. For these patients, who are frequently unfit for further surgery, radiotherapy is the principal locoregional option, but the evidence base is thin and largely retrospective. This review summarizes current knowledge on the patterns and determinants of postoperative recurrence, the diagnostic work-up required before salvage treatment, and the radiotherapy strategies available for anastomotic recurrence and regional nodal disease. The roles of conventional external-beam radiotherapy, intensity-modulated radiotherapy, stereotactic body radiotherapy and particle therapy are compared, with particular attention to dose constraints in the re-irradiation setting. The toxicity–efficacy balance and the biological mechanisms underlying radioresistance are then considered; how best to combine radiotherapy with systemic agents, including immune-checkpoint blockade, remains an open question. Because prospective data specific to this setting remain scarce, treatment decisions still rest on individualized, multidisciplinary assessment.

Downloads

Download data is not yet available.

References

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-63.

Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024;4(1):47-53.

Lou F, Sima CS, Adusumilli PS, Bains MS, Sarkaria IS, Rusch VW, et al. Esophageal cancer recurrence patterns and implications for surveillance. Journal of thoracic oncology. 2013;8(12):1558-62.

Cui T, Chen H, Fan M, Huang W, Liu X. Identifying risk factors and evaluating therapeutic interventions for anastomotic recurrence in postoperative esophageal squamous cell carcinoma. BMC cancer. 2025;25(1):1245.

Carr RA, Harrington C, Vos E, Bains MS, Bott MJ, Isbell JM, et al. Treatment of anastomotic recurrence after esophagectomy. The Annals of thoracic surgery. 2022;114(2):418-25.

Xiong J, Liang S, Lu S, Chen H, Wang Z, Meng H, et al. The impact of perineural invasion on prognosis in esophageal cancer patients after surgery: a systematic review and meta-analysis. Frontiers in Oncology. 2025;Volume 15 - 2025.

Hosch SB, Stoecklein NH, Pichlmeier U, Rehders A, Scheunemann P, Niendorf A, et al. Esophageal cancer: the mode of lymphatic tumor cell spread and its prognostic significance. Journal of clinical oncology. 2001;19(7):1970-5.

Prenzel KL, Bollschweiler E, Schröder W, Mönig SP, Drebber U, Vallboehmer D, et al. Prognostic relevance of skip metastases in esophageal cancer. The Annals of thoracic surgery. 2010;90(5):1662-7.

Liu G, Hu B, Chen T, Zhang X, Tang Y, Chen Q, et al. Recurrence timing and patterns incorporating lymph node status after neoadjuvant chemoradiotherapy plus esophagectomy for esophageal squamous cell carcinoma. Frontiers in Oncology. 2024;14:1310073.

Lee S, Lee K, Yim Y, Kim T, Shim Y, Kim K. Recurrence of squamous cell carcinoma of the oesophagus after curative surgery: rates and patterns on imaging studies correlated with tumour location and pathological stage. Clinical radiology. 2005;60(5):547-54.

Kim TJ, Lee KH, Kim YH, Sung SW, Jheon S, Cho S-k, et al. Postoperative imaging of esophageal cancer: what chest radiologists need to know. Radiographics. 2007;27(2):409-29.

Sun L, Su X-H, Guan Y-S, Pan W-M, Luo Z-M, Wei J-H, et al. Clinical usefulness of 18F-FDG PET/CT in the restaging of esophageal cancer after surgical resection and radiotherapy. World journal of gastroenterology: WJG. 2009;15(15):1836.

Wang S, Wang S, Liu W, Sun S, Liu X, Ge N, et al. The application of linear endoscopic ultrasound in the patients with esophageal anastomotic strictures. Endoscopic Ultrasound. 2015;4(2):126.

Huang Y, Liu F, Xu R, Zhou F, Yang W, He Y, et al. Postoperative serum squamous cell carcinoma antigen and carcinoembryonic antigen predict overall survival in surgical patients with esophageal squamous cell carcinoma. Frontiers in Oncology. 2023;13:1263990.

Ng HY, Ko JMY, Lam KO, Kwong DLW, Lo AWI, Wong IYH, et al. Circulating tumor DNA dynamics as prognostic markers in locally advanced and metastatic esophageal squamous cell carcinoma. JAMA surgery. 2023;158(11):1141-50.

Ito R, Nakamura Y, Sunakawa H, Fujiwara H, Hojo H, Nakamura N, et al. Tumor response and survival outcomes of salvage concurrent chemoradiotherapy with three-dimensional conformal radiotherapy and 5-fluorouracil/platinum-based chemotherapy for postoperative locoregional recurrence of esophageal squamous cell carcinoma. Esophagus. 2022;19:645 - 52.

Zhang J, Peng F, Li N, Liu Y, Xu Y, Zhou L, et al. Salvage concurrent radio-chemotherapy for post-operative local recurrence of squamous-cell esophageal cancer. Radiation oncology. 2012;7(1):93.

Xu D, Li G, Li H, Jia F. Comparison of IMRT versus 3D-CRT in the treatment of esophagus cancer: A systematic review and meta-analysis. Medicine. 2017;96(31):e7685.

Chandra A, Guerrero TM, Liu HH, Tucker SL, Liao Z, Wang X, et al. Feasibility of using intensity-modulated radiotherapy to improve lung sparing in treatment planning for distal esophageal cancer. Radiotherapy and Oncology. 2005;77(3):247-53.

Moraes FYd, Taunk NK, Laufer I, Neves-Junior WFP, Hanna SA, Carvalho HdA, et al. Spine radiosurgery for the local treatment of spine metastases: Intensity-modulated radiotherapy, image guidance, clinical aspects and future directions. Clinics. 2016;71(2):101-9.

Remick JS, Schonewolf C, Gabriel P, Doucette A, Levin WP, Kucharczuk JC, et al. First clinical report of proton beam therapy for postoperative radiotherapy for non–small-cell lung cancer. Clinical lung cancer. 2017;18(4):364-71.

Kong L, Gao J, Hu J, Hu W, Guan X, Lu R, et al. Phase I/II trial evaluating concurrent carbon‐ion radiotherapy plus chemotherapy for salvage treatment of locally recurrent nasopharyngeal carcinoma. Cancer Communications. 2016;35(1):1-11.

Zhu H, del Campo ER, Ye J, Simone II CB, Zhu Z, Zhao W, et al. Involved-field irradiation in definitive chemoradiotherapy for locoregional esophageal squamous cell carcinoma: results from the ESO-Shanghai 1 trial. International Journal of Radiation Oncology* Biology* Physics. 2021;110(5):1396-406.

Al-Sarraf M, Martz K, Herskovic A, Leichman L, Brindle J, Vaitkevicius V, et al. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. Journal of Clinical Oncology. 1997;15(1):277-84.

Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. Journal of clinical oncology. 2002;20(5):1167-74.

Chen M-F, Chen P-T, Chen W-C, Lu M-S, Lin P-Y, Lee K-D. The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression. Oncotarget. 2016;7(7):7913.

Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Van Cutsem E, Piessen G, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. New England Journal of Medicine. 2021;384(13):1191-203.

Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, et al. Effect of camrelizumab vs placebo added to chemotherapy on survival and progression-free survival in patients with advanced or metastatic esophageal squamous cell carcinoma: the ESCORT-1st randomized clinical trial. Jama. 2021;326(10):916-25.

Zhang C, Ge X-L, Huang C-J, Zhang S, Sun X-C. Outcomes and prognostic factors of salvage radiation for postoperative lymph node recurrence of esophageal squamous cell carcinoma. Frontiers in Oncology. 2021;11:638521.

Parry K, Visser E, van Rossum PS, Mohammad NH, Ruurda JP, van Hillegersberg R. Prognosis and treatment after diagnosis of recurrent esophageal carcinoma following esophagectomy with curative intent. Annals of surgical oncology. 2015;22(Suppl 3):1292-300.

Yamashita H, Jingu K, Niibe Y, Katsui K, Matsumoto T, Nishina T, et al. Definitive salvage radiation therapy and chemoradiation therapy for lymph node oligo-recurrence of esophageal cancer: a Japanese multi-institutional study of 237 patients. Radiation Oncology. 2017;12(1):38.

Ihara H, Yoshio K, Tanabe S, Sugiyama S, Hashimoto M, Maeda N, et al. Outcomes of solitary postoperative recurrence of esophageal squamous cell carcinoma diagnosed with FDG-PET/CT and treated with definitive radiation therapy. Esophagus. 2023;20(3):548-56.

Mummudi N, Jiwnani S, Niyogi D, Srinivasan S, Ghosh-Laskar S, Tibdewal A, et al. Salvage radiotherapy for postoperative locoregional failure in esophageal cancer: a systematic review and meta-analysis. Diseases of the Esophagus. 2022;35(3):doab020.

Liu G-F, Chang H, Li B-T, Zhang Y, Li D-D, Liu Y, et al. Effect of recombinant human endostatin onradiotherapy for esophagus cancer. Asian Pacific Journal of Tropical Medicine. 2016;9(1):86-90.

Yang X-X, Sang M-X, Zhu S-C, Liu Z-K, Ma M. Radiosensitization of esophageal carcinoma cells by the silencing of BMI-1. Oncology Reports. 2016;35(6):3669-78.

Lin C-H, Tsai C-H, Yeh C-T, Liang J-L, Hung W-C, Lin F-C, et al. MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma. Oncotarget. 2016;7(26):39680.

Wang Y, Wu J, Guo W, Sun Q, Chen X, Zang W, et al. α-solanine modulates the radiosensitivity of esophageal cancer cells by inducing microRNA 138 expression. Cellular Physiology and Biochemistry. 2016;39(3):996-1010.