Abstract
Background
Pathologic complete lymph node regression (LNR), where the lymph nodes show evidence of neoadjuvant treatment effect but have no viable residual tumor cells, is sometimes observed following neoadjuvant treatments and has been shown to be prognostic; conflicting results exist in the current literature.
Methods
Patients who received neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy for squamous carcinoma (ESCC) were retrospectively reviewed and classified according to their LNR score; 0: N(−) with no evidence of tumor involvement or regression; 1: N(−) with evidence of complete regression; 2: N(+) with < 50% viable tumor; and 3: N(+) with > 50% viable tumor.
Results
In total, 136 patients, comprising 73, 25, 16, and 22 patients with LNR scores of 0, 1, 2, or 3, respectively, were included. Pathologic complete LNR (LNR 1) was significantly associated with lower risks of lymphovascular invasion (0%, p < 0.001) and perineural invasion (4%, p = 0.038), and a higher rate of pathologic complete response in the primary tumor (76%, p < 0.001). The 5-year overall survival rates were 42.1%, 52.8%, and 8.0% in patients with an LNR score of 0, 1, and 2/3, respectively (p < 0.001). There was no significant difference between patients with LNR scores of 0 and 1 in overall survival (p = 0.454), disease-free survival (p = 0.501), and cumulative incidence of recurrences (hazard ratio 0.84, 95% confidence interval 0.432–1.623, p = 0.601).
Conclusions
Pathologic complete LNR could be an indicator of nCRT sensitivity and can be regarded as a good prognostic factor in patients with ESCC.
Graphic Abstract
In the survival curve analysis that included patients with lymph node regression (LNR) scores of 0 (blue), 1 (red), and 2/3 (green), we found that patients with pathologic complete LNR (LNR 1), which suggests prior positive nodal involvement, had similar outcomes as those without evidence of prior tumor involvement in lymph node (LNR0).
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References
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.
Jang R, Darling G, Wong RK. Multimodality approaches for the curative treatment of esophageal cancer. J Natl Compr Canc Netw. 2015;13:229–-238.
Hölscher AH, Drebber U, Schmidt H, et al. Prognostic classification of histopathologic response to neoadjuvant therapy in esophageal adenocarcinoma. Ann Surg. 2014;260:779–784.
Berger AC, Farma J, Scott WJ, et al. Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival. J Clin Oncol. 2005;23:4330–4337.
Tong DK, Law S, Kwong DL, et al. Histological regression of squamous esophageal carcinoma assessed by percentage of residual viable cells after neoadjuvant chemoradiation is an important prognostic factor. Ann Surg Oncol. 2010;17:2184–2192.
Nieman DR, Peyre CG, Watson TJ, et al. Neoadjuvant treatment response in negative nodes is an important prognosticator after esophagectomy. Ann Thorac Surg. 2015;99:277–283.
Philippron A, Bollschweiler E, Kunikata A, et al. Prognostic relevance of lymph node regression after neoadjuvant chemoradiation for esophageal cancer. Semin Thorac Cardiovasc Surg. 2016;28:549–558.
Davies AR, Myoteri D, Zylstra J, et al. Lymph node regression and survival following neoadjuvant chemotherapy in oesophageal adenocarcinoma. Br J Surg. 2018;105:1639–1649.
Kadota T, Hatogai K, Yano T, et al. Pathological tumor regression grade of metastatic tumors in lymph node predicts prognosis in esophageal cancer patients. Cancer Sci. 2018;109:2046–2055.
Chirieac LR, Swisher SG, Ajani JA, et al. Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer. 2005;103:1347–1355.
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.
Groth SS, Burt BM, Farjah F, et al. Prognostic value of neoadjuvant treatment response in locally advanced esophageal adenocarcinoma. J Thorac Cardiovasc Surg. 2019;157:1682–1693.
Urakawa S, Makino T, Yamasaki M, et al. Lymph Node Response to Neoadjuvant Chemotherapy as an Independent Prognostic Factor in Metastatic Esophageal Cancer. Ann Surg. 2019. https://doi.org/10.1097/SLA.0000000000003445.
Chien HC, Chen HS, Wu SC, et al. The prognostic value of metastatic lymph node number and ratio in oesophageal squamous cell carcinoma patients with or without neoadjuvant chemoradiation. Eur J Cardiothorac Surg. 2016;50:337–343.
Robb WB, Dahan L, Mornex F, et al. Impact of neoadjuvant chemoradiation on lymph node status in esophageal cancer: post hoc analysis of a randomized controlled trial. Ann Surg. 2015;261:902–908.
Rice TW, Patil DT, Blackstone EH. 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice. Ann Cardiothorac Surg. 2017;6:119–30.
Yoon YC, Lee KS, Shim YM, et al. Metastasis to regional lymph nodes in patients with esophageal squamous cell carcinoma: CT versus FDG PET for presurgical detection prospective study. Radiology. 2003;227:764–770.
Acknowledgment
The authors thank Hsin-Yi Huang from the Biostatistics Task Force, Taipei Veterans General Hospital, for statistical assistance.
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No sources of funding were used to assist in the preparation of this study.
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Po-Kuei Hsu, Yi-Chen Yeh, Ling-I Chien, Chien-Sheng Huang, and Han-Shui Hsu have no conflicts of interest to declare.
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Hsu, PK., Yeh, YC., Chien, LI. et al. Clinicopathological Significance of Pathologic Complete Lymph Node Regression After Neoadjuvant Chemoradiotherapy in Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 28, 2048–2058 (2021). https://doi.org/10.1245/s10434-020-09363-z
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DOI: https://doi.org/10.1245/s10434-020-09363-z