Risk factors associated with postoperative adjuvant therapy for resectable esophageal squamous cell carcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZENG Teng ^1,2 , HE Rui ¹ , CHEN Xiaobo ¹ , MING Chao ¹ ,  ZHAO Guangqiang ¹

1. Department of Thoracic Surgery Ⅰ, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, P. R. China;
2. Department of Thoracic Surgery, Northeast Yunnan Central Hospital, Zhaotong, 657000, Yunnan, P. R. China;

Corresponding?author：

ZHAO Guangqiang, Email: zgqst2012@163.com

Keywords：

Esophageal squamous cell carcinoma; adjuvant therapy; risk factors; lymph node metastasis; prognosis; individualized therapy; molecular biomarker; review

DOI：

10.7507/1007-4848.202401017

Video：

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The benefit of postoperative adjuvant therapy for patients with resectable esophageal squamous cell carcinoma (ESCC) is not yet supported by high-level evidence. This review analyzes the role of adjuvant therapy by examining the discrepancy between clinical needs and guidelines, its historical evolution, recent advances in high-risk factors, and future outlooks. We provide a detailed discussion of high-risk factors used for patient selection, including lymph node positivity, and for node-negative patients, features such as tumor length, location, T stage, extent of lymph node dissection, differentiation, vascular and neural invasion, laboratory indices, and molecular markers. The goal is to inform the development of individualized precision treatment strategies for resectable ESCC.

Citation： ZENG Teng, HE Rui, CHEN Xiaobo, MING Chao, ZHAO Guangqiang. Risk factors associated with postoperative adjuvant therapy for resectable esophageal squamous cell carcinoma. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2026, 33(2): 326-332. doi: 10.7507/1007-4848.202401017 Copy

1.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020, 70(1): 7-30.
2.	Liang H, Fan JH, Qiao YL. Epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China. Cancer Biol Med, 2017, 14(1): 33-41.
3.	中國臨床腫瘤學會指南工作委員會. 中國臨床腫瘤學會 (CSCO) 食管癌診療指南2023. 北京: 人民衛生出版社. 1-125.Guidelines Working Committee of the Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) Guidelines for the Treatment of Esophageal Cancer 2023. Beijing: People's Medical Publishing House. 1-125.
4.	Crosby T, Evans M, Gillies RS, et al. The management of a patient with an operable carcinoma of the oesophagus. Ann R Coll Surg Engl, 2009, 91(5): 366-370.
5.	Ando N, Iizuka T, Kakegawa T, et al. A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: the Japan Clinical Oncology Group Study. J Thorac Cardiovasc Surg, 1997, 114(2): 205-209.
6.	Ando N, Iizuka T, Ide H, et al. Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study—JCOG9204. J Clin Oncol, 2003, 21(24): 4592-4596.
7.	Ando N, Kato H, Igaki H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol, 2012, 19(1): 68-74.
8.	Zieren HU, Müller JM, Jacobi CA, et al. Adjuvant postoperative radiation therapy after curative resection of squamous cell carcinoma of the thoracic esophagus: a prospective randomized study. World J Surg, 1995, 19(3): 444-449.
9.	Deng W, Yang J, Ni W, et al. Postoperative radiotherapy in pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma: interim report of a prospective, phase Ⅲ, randomized controlled study. Oncologist, 2020, 25(4): e701-e708.
10.	Zhu K, Ren P, Yang Y, et al. Role of chemotherapy after curative esophagectomy in squamous cell carcinoma of the thoracic esophagus: a propensity score-matched analysis. Thorac Cancer, 2021, 12(12): 1800-1809.
11.	Hsu PK, Huang CS, Wang BY, et al. Survival benefits of postoperative chemoradiation for lymph node-positive esophageal squamous cell carcinoma. Ann Thorac Surg, 2014, 97(5): 1734-1741.
12.	Tachibana M, Yoshimura H, Kinugasa S, et al. Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial. Eur J Surg Oncol, 2003, 29(7): 580-587.
13.	Lee J, Lee KE, Im YH, et al. Adjuvant chemotherapy with 5-fluorouracil and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma. Ann Thorac Surg, 2005, 80(4): 1170-1175.
14.	Zhang SS, Yang H, Xie X, et al. Adjuvant chemotherapy versus surgery alone for esophageal squamous cell carcinoma: a meta-analysis of randomized controlled trials and nonrandomized studies. Dis Esophagus, 2014, 27(6): 574-584.
15.	Ni W, Chen J, Xiao Z, et al. Adjuvant radiotherapy for stage pN1M0 esophageal squamous cell carcinoma: results from a Chinese two-center study. Thorac Cancer, 2019, 10(6): 1431-1440.
16.	Wang Q, Lang J, Li T, et al. Postoperative adjuvant chemotherapy versus chemoradiotherapy for node-positive esophageal squamous cell carcinoma: a propensity score-matched analysis. Radiat Oncol, 2020, 15(1): 119.
17.	Jeon YJ, Cho JH, Choi YS, et al. Adjuvant chemotherapy in node-positive patients after esophagectomy for esophageal squamous cell carcinoma. Thorac Cancer, 2023, 14(6): 624-635.
18.	Yang W, Liu F, Xu R, et al. Is adjuvant therapy a better option for esophageal squamous cell carcinoma patients treated with esophagectomy? A prognosis prediction model based on multicenter real-world data. Ann Surg, 2023, 277(1): e61-e69.
19.	Chen SB, Liu DT, Chen YP. Impact of adjuvant chemotherapy for radically resected esophageal squamous cell carcinoma: a propensity score matching analysis. Front Surg, 2023, 10: 1181505.
20.	Feng SK, Liu XB, Xing WQ, et al. Adjuvant chemotherapy for node-positive esophageal squamous cell carcinoma improves survival. Ann Thorac Surg, 2022, 114(4): 1205-1213.
21.	Gao HJ, Shang XB, Gong L, et al. Adjuvant radiotherapy for patients with pathologic node-negative esophageal carcinoma: a population based propensity matching analysis. Thorac Cancer, 2020, 11(2): 243-252.
22.	Gao H, Wang Y, Jiang Z, et al. Association of survival with adjuvant radiotherapy for pN0 esophageal cancer. Aging (Albany NY), 2023, 15(8): 3158-3170.
23.	Zhang X, Yang Y, Sun Y, et al. Adjuvant therapy for pathological T3N0M0 esophageal squamous cell carcinoma. J Thorac Dis, 2019, 11(6): 2512-2522.
24.	Yang J, Zhang W, Xiao Z, et al. The impact of postoperative conformal radiotherapy after radical surgery on survival and recurrence in pathologic T3N0M0 esophageal carcinoma: a propensity score-matched analysis. J Thorac Oncol, 2017, 12(7): 1143-1151.
25.	Wang Q, Peng L, Li T, et al. Postoperative chemotherapy for thoracic pathological T3N0M0 esophageal squamous cell carcinoma. Ann Surg Oncol, 2020, 27(5): 1488-1495.
26.	Guo YN, Tian DP, Gong QY, et al. Perineural invasion is a better prognostic indicator than lymphovascular invasion and a potential adjuvant therapy indicator for pN0M0 esophageal squamous cell carcinoma. Ann Surg Oncol, 2020, 27(11): 4371-4381.
27.	Xie C, Chen Z, Xu J, et al. Influence of Lymphangio vascular (V) and perineural (N) invasion on survival of patients with resected esophageal squamous cell carcinoma (ESCC): a single-center retrospective study. Peer J, 2022, 10: e12974.
28.	Wang Q, Peng L, Han Y, et al. Preoperative serum sodium level as a prognostic and predictive biomarker for adjuvant therapy in esophageal cancer. Front Oncol, 2021, 10: 555714.
29.	Zhang W, Jia H, Chen X, et al. Prognostic significance and postoperative chemoradiotherapy guiding value of mean platelet volume for locally advanced esophageal squamous cell carcinoma patients. Front Oncol, 2023, 13: 1094040.
30.	Wang S, Wang Z, Yang Z, et al. Postoperative radiotherapy improves survival in stage pT2N0M0 esophageal squamous cell carcinoma with high risk of poor prognosis. Ann Surg Oncol, 2016, 23(1): 265-272.
31.	Yang Y, Huang X, Zhou L, et al. Clinical use of tumor biomarkers in prediction for prognosis and chemotherapeutic effect in esophageal squamous cell carcinoma. BMC Cancer, 2019, 19(1): 526.
32.	Piva VM, De Grandis MC, Zuin IS, et al. ctDNA as promising tool for the assessment of minimal residual disease (MRD) and the need of an adjuvant treatment in gastroesophageal adenocarcinoma. Updates Surg, 2023, 75(2): 305-312.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020, 70(1): 7-30.
2. Liang H, Fan JH, Qiao YL. Epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China. Cancer Biol Med, 2017, 14(1): 33-41.
3. 中國臨床腫瘤學會指南工作委員會. 中國臨床腫瘤學會 (CSCO) 食管癌診療指南2023. 北京: 人民衛生出版社. 1-125.Guidelines Working Committee of the Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) Guidelines for the Treatment of Esophageal Cancer 2023. Beijing: People's Medical Publishing House. 1-125.
4. Crosby T, Evans M, Gillies RS, et al. The management of a patient with an operable carcinoma of the oesophagus. Ann R Coll Surg Engl, 2009, 91(5): 366-370.
5. Ando N, Iizuka T, Kakegawa T, et al. A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: the Japan Clinical Oncology Group Study. J Thorac Cardiovasc Surg, 1997, 114(2): 205-209.
6. Ando N, Iizuka T, Ide H, et al. Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study—JCOG9204. J Clin Oncol, 2003, 21(24): 4592-4596.
7. Ando N, Kato H, Igaki H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol, 2012, 19(1): 68-74.
8. Zieren HU, Müller JM, Jacobi CA, et al. Adjuvant postoperative radiation therapy after curative resection of squamous cell carcinoma of the thoracic esophagus: a prospective randomized study. World J Surg, 1995, 19(3): 444-449.
9. Deng W, Yang J, Ni W, et al. Postoperative radiotherapy in pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma: interim report of a prospective, phase Ⅲ, randomized controlled study. Oncologist, 2020, 25(4): e701-e708.
10. Zhu K, Ren P, Yang Y, et al. Role of chemotherapy after curative esophagectomy in squamous cell carcinoma of the thoracic esophagus: a propensity score-matched analysis. Thorac Cancer, 2021, 12(12): 1800-1809.
11. Hsu PK, Huang CS, Wang BY, et al. Survival benefits of postoperative chemoradiation for lymph node-positive esophageal squamous cell carcinoma. Ann Thorac Surg, 2014, 97(5): 1734-1741.
12. Tachibana M, Yoshimura H, Kinugasa S, et al. Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial. Eur J Surg Oncol, 2003, 29(7): 580-587.
13. Lee J, Lee KE, Im YH, et al. Adjuvant chemotherapy with 5-fluorouracil and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma. Ann Thorac Surg, 2005, 80(4): 1170-1175.
14. Zhang SS, Yang H, Xie X, et al. Adjuvant chemotherapy versus surgery alone for esophageal squamous cell carcinoma: a meta-analysis of randomized controlled trials and nonrandomized studies. Dis Esophagus, 2014, 27(6): 574-584.
15. Ni W, Chen J, Xiao Z, et al. Adjuvant radiotherapy for stage pN1M0 esophageal squamous cell carcinoma: results from a Chinese two-center study. Thorac Cancer, 2019, 10(6): 1431-1440.
16. Wang Q, Lang J, Li T, et al. Postoperative adjuvant chemotherapy versus chemoradiotherapy for node-positive esophageal squamous cell carcinoma: a propensity score-matched analysis. Radiat Oncol, 2020, 15(1): 119.
17. Jeon YJ, Cho JH, Choi YS, et al. Adjuvant chemotherapy in node-positive patients after esophagectomy for esophageal squamous cell carcinoma. Thorac Cancer, 2023, 14(6): 624-635.
18. Yang W, Liu F, Xu R, et al. Is adjuvant therapy a better option for esophageal squamous cell carcinoma patients treated with esophagectomy? A prognosis prediction model based on multicenter real-world data. Ann Surg, 2023, 277(1): e61-e69.
19. Chen SB, Liu DT, Chen YP. Impact of adjuvant chemotherapy for radically resected esophageal squamous cell carcinoma: a propensity score matching analysis. Front Surg, 2023, 10: 1181505.
20. Feng SK, Liu XB, Xing WQ, et al. Adjuvant chemotherapy for node-positive esophageal squamous cell carcinoma improves survival. Ann Thorac Surg, 2022, 114(4): 1205-1213.
21. Gao HJ, Shang XB, Gong L, et al. Adjuvant radiotherapy for patients with pathologic node-negative esophageal carcinoma: a population based propensity matching analysis. Thorac Cancer, 2020, 11(2): 243-252.
22. Gao H, Wang Y, Jiang Z, et al. Association of survival with adjuvant radiotherapy for pN0 esophageal cancer. Aging (Albany NY), 2023, 15(8): 3158-3170.
23. Zhang X, Yang Y, Sun Y, et al. Adjuvant therapy for pathological T3N0M0 esophageal squamous cell carcinoma. J Thorac Dis, 2019, 11(6): 2512-2522.
24. Yang J, Zhang W, Xiao Z, et al. The impact of postoperative conformal radiotherapy after radical surgery on survival and recurrence in pathologic T3N0M0 esophageal carcinoma: a propensity score-matched analysis. J Thorac Oncol, 2017, 12(7): 1143-1151.
25. Wang Q, Peng L, Li T, et al. Postoperative chemotherapy for thoracic pathological T3N0M0 esophageal squamous cell carcinoma. Ann Surg Oncol, 2020, 27(5): 1488-1495.
26. Guo YN, Tian DP, Gong QY, et al. Perineural invasion is a better prognostic indicator than lymphovascular invasion and a potential adjuvant therapy indicator for pN0M0 esophageal squamous cell carcinoma. Ann Surg Oncol, 2020, 27(11): 4371-4381.
27. Xie C, Chen Z, Xu J, et al. Influence of Lymphangio vascular (V) and perineural (N) invasion on survival of patients with resected esophageal squamous cell carcinoma (ESCC): a single-center retrospective study. Peer J, 2022, 10: e12974.
28. Wang Q, Peng L, Han Y, et al. Preoperative serum sodium level as a prognostic and predictive biomarker for adjuvant therapy in esophageal cancer. Front Oncol, 2021, 10: 555714.
29. Zhang W, Jia H, Chen X, et al. Prognostic significance and postoperative chemoradiotherapy guiding value of mean platelet volume for locally advanced esophageal squamous cell carcinoma patients. Front Oncol, 2023, 13: 1094040.
30. Wang S, Wang Z, Yang Z, et al. Postoperative radiotherapy improves survival in stage pT2N0M0 esophageal squamous cell carcinoma with high risk of poor prognosis. Ann Surg Oncol, 2016, 23(1): 265-272.
31. Yang Y, Huang X, Zhou L, et al. Clinical use of tumor biomarkers in prediction for prognosis and chemotherapeutic effect in esophageal squamous cell carcinoma. BMC Cancer, 2019, 19(1): 526.
32. Piva VM, De Grandis MC, Zuin IS, et al. ctDNA as promising tool for the assessment of minimal residual disease (MRD) and the need of an adjuvant treatment in gastroesophageal adenocarcinoma. Updates Surg, 2023, 75(2): 305-312.

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