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Newly developed primary malignancies in long-term survivors who underwent curative esophagectomy for squamous cell carcinoma of the esophagus

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We evaluated the efficacy of the long-term follow-up of patients who underwent radical esophagectomy for esophageal squamous cell carcinoma (ESCC) to screen for recurrence and new primary malignancies.


We retrospectively collected 448 ESCC patients who underwent radical esophagectomy. Esophagogastroduodenoscopy, computed tomography, a stool test and the assessment of the serum concentration of squamous cell carcinoma antigen and carcinoembryonic antigen were performed annually, even over 5 years after esophagectomy. The incidence of ESCC recurrence and new primary malignancies was investigated.


We enrolled 222 patients who survived at least 5 years after esophagectomy. A total of 104 new primary malignancies occurred in 82 patients (36.9%) after esophagectomy. Twenty-one malignancies were in the head and neck region, 14 in the residual esophagus, 13 in the prostate and 11 in the gastric tube and lung. Patients who developed new primary malignancies after esophagectomy had a significantly higher Brinkman index than those without new malignancies. An endoscopic approach successfully treated 92.9% of carcinomas in the residual esophagus, 90.9% of cancers in the gastric tube and 42.9% of carcinomas in the head and neck region.


The incidence of new primary malignancies was higher than the age-standardized incidence. Long-term follow-up and systemic screening may increase the probability of an early diagnosis and subsequent low-invasive treatment.

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  1. WHO. Cancer today; 2020.

  2. Malhotra GK, Yanala U, Ravipati A, Follet M, Vijayakumar M, Are C. Global trends in esophageal cancer. J Surg Oncol. 2017;115(5):564–79.

    PubMed  Google Scholar 

  3. Kanda M, Koike M, Shimizu D, Tanaka C, Kobayashi D, Hattori N, et al. optimized cutoff value of serum squamous cell carcinoma antigen concentration accurately predicts recurrence after curative resection of squamous cell carcinoma of the esophagus. Ann Surg Oncol. 2019.

  4. Lagergren J, Smyth E, Cunningham D, Lagergren P. Oesophageal cancer. Lancet. 2017;390(10110):2383–96.

    PubMed  Google Scholar 

  5. Kanda M, Koike M, Tanaka C, Kobayashi D, Hayashi M, Yamada S, et al. Risk prediction of postoperative pneumonia after subtotal esophagectomy based on preoperative serum cholinesterase concentrations. Ann Surg Oncol. 2019;26(11):3718–26.

    PubMed  Google Scholar 

  6. Kato K, Nakajima TE, Ito Y, Katada C, Ishiyama H, Tokunaga SY, et al. Phase II study of concurrent chemoradiotherapy at the dose of 50.4 Gy with elective nodal irradiation for Stage II-III esophageal carcinoma. Jpn J Clin Oncol. 2013;43(6):608–15.

    PubMed  Google Scholar 

  7. Yokota T, Kato K, Hamamoto Y, Tsubosa Y, Ogawa H, Ito Y, et al. Phase II study of chemoselection with docetaxel plus cisplatin and 5-fluorouracil induction chemotherapy and subsequent conversion surgery for locally advanced unresectable oesophageal cancer. Br J Cancer. 2016;115(11):1328–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Kato K, Cho BC, Takahashi M, Okada M, Lin CY, Chin K, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(11):1506–17.

    CAS  PubMed  Google Scholar 

  9. Kontis V, Bennett JE, Mathers CD, Li G, Foreman K, Ezzati M. Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble. Lancet. 2017;389(10076):1323–35.

    PubMed  PubMed Central  Google Scholar 

  10. Kanda M, Koike M, Tanaka C, Kobayashi D, Hayashi M, Yamada S, et al. Feasibility of subtotal esophagectomy with systematic lymphadenectomy in selected elderly patients with esophageal cancer; a propensity score matching analysis. BMC Surg. 2019;19(1):143.

    PubMed  PubMed Central  Google Scholar 

  11. Peixoto RD, Lim HJ, Kim H, Abdullah A, Cheung WY. Patterns of surveillance following curative intent therapy for gastroesophageal cancer. J Gastrointest Cancer. 2014;45(3):325–33.

    CAS  PubMed  Google Scholar 

  12. Polinder S, Verschuur EM, Siersema PD, Kuipers EJ, Steyerberg EW. Cost comparison study of two different follow-up protocols after surgery for oesophageal cancer. Eur J Cancer. 2009;45(12):2110–5.

    PubMed  Google Scholar 

  13. Katada C, Yokoyama T, Yano T, Kaneko K, Oda I, Shimizu Y, et al. Alcohol consumption and multiple dysplastic lesions increase risk of squamous cell carcinoma in the esophagus, head, and neck. Gastroenterology. 2016;151(5):860–9.e7.

    CAS  PubMed  Google Scholar 

  14. Abnet CC, Arnold M, Wei WQ. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology. 2018;154(2):360–73.

    PubMed  Google Scholar 

  15. Tian D, Feng Z, Hanley NM, Setzer RW, Mumford JL, DeMarini DM. Multifocal accumulation of p53 protein in esophageal carcinoma: evidence for field cancerization. Int J Cancer. 1998;78(5):568–75.

    CAS  PubMed  Google Scholar 

  16. Fitzpatrick PJ, Tepperman BS, deBoer G. Multiple primary squamous cell carcinomas in the upper digestive tract. Int J Radiat Oncol Biol Phys. 1984;10(12):2273–9.

    CAS  PubMed  Google Scholar 

  17. Hayes RB, Ahn J, Fan X, Peters BA, Ma Y, Yang L, et al. Association of oral microbiome with risk for incident head and neck squamous cell cancer. JAMA Oncol. 2018;4(3):358–65.

    PubMed  PubMed Central  Google Scholar 

  18. Yamamura K, Baba Y, Nakagawa S, Mima K, Miyake K, Nakamura K, et al. Human microbiome fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis. Clin Cancer Res. 2016;22(22):5574–81.

    CAS  PubMed  Google Scholar 

  19. Hashimoto K, Shimizu D, Hirabayashi S, Ueda S, Miyabe S, Oh-Iwa I, et al. Changes in oral microbial profiles associated with oral squamous cell carcinoma vs leukoplakia. J Investig Clin Dent. 2019:e12445.

  20. Chen D, Fan N, Mo J, Wang W, Wang R, Chen Y, et al. Multiple primary malignancies for squamous cell carcinoma and adenocarcinoma of the esophagus. J Thorac Dis. 2019;11(8):3292–301.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Sato Y, Motoyama S, Maruyama K, Okuyama M, Ogawa J. A second malignancy is the major cause of death among thoracic squamous cell esophageal cancer patients negative for lymph node involvement. J Am Coll Surg. 2005;201(2):188–93.

    PubMed  Google Scholar 

  22. Natsugoe S, Matsumoto M, Okumura H, Ishigami S, Uenosono Y, Owaki T, et al. Multiple primary carcinomas with esophageal squamous cell cancer: clinicopathologic outcome. World J Surg. 2005;29(1):46–9.

    PubMed  Google Scholar 

  23. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer. 2017;20(1):1–19.

  24. Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol. 2018;23(1):1–34.

    PubMed  Google Scholar 

  25. Kitagawa Y, Uno T, Oyama T, Kato K, Kato H, Kawakubo H, et al. Esophageal cancer practice guidelines 2017 edited by the Japan Esophageal Society: part 1. Esophagus. 2019;16(1):1–24.

    PubMed  Google Scholar 

  26. Kitagawa Y, Uno T, Oyama T, Kato K, Kato H, Kawakubo H, et al. Esophageal cancer practice guidelines 2017 edited by the Japan esophageal society: part 2. Esophagus. 2019;16(1):25–43.

    PubMed  Google Scholar 

  27. Chuang SC, Hashibe M, Scelo G, Brewster DH, Pukkala E, Friis S, et al. Risk of second primary cancer among esophageal cancer patients: a pooled analysis of 13 cancer registries. Cancer Epidemiol Biomarkers Prev. 2008;17(6):1543–9.

    PubMed  Google Scholar 

  28. Natsugoe S, Uchino Y, Kijima F, Shimada M, Shirao K, Kusano C, et al. Synchronous and metachronous carcinomas of the esophagus and head and neck. Dis Esophagus. 1997;10(2):134–8.

    CAS  PubMed  Google Scholar 

  29. Kato M, Ishihara R, Hamada K, Tonai Y, Yamasaki Y, Matsuura N, et al. Endoscopic surveillance of head and neck cancer in patients with esophageal squamous cell carcinoma. Endosc Int Open. 2016;4(7):E752–E755755.

    PubMed  PubMed Central  Google Scholar 

  30. Katada C, Muto M, Tanabe S, Higuchi K, Sasaki T, Azuma M, et al. Surveillance after endoscopic mucosal resection or endoscopic submucosal dissection for esophageal squamous cell carcinoma. Dig Endosc. 2013;25(Suppl 1):39–433.

    PubMed  Google Scholar 

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We thank Edanz Group ( for editing a draft of this manuscript.

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Correspondence to Dai Shimizu.

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Shimizu, D., Koike, M., Kanda, M. et al. Newly developed primary malignancies in long-term survivors who underwent curative esophagectomy for squamous cell carcinoma of the esophagus. Surg Today 51, 153–158 (2021).

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