Esophageal cancer (EC) remains one of the most lethal malignancies of the gastrointestinal tract (GI) worldwide despite advances in medical and surgical care. Both squamous cell carcinoma (SCC) and adenocarcinoma (AC) stand out as the two most common types, with distinction in geographic distribution.Citation1 SCC predominates in Asia, while adenocarcinoma predominates in Europe and the United States.Citation1,Citation2 Diagnosis of EC at early stages has a favorable impact on survival; however, routine screening is not standardized globally, except for some areas such as China and Japan. Therefore, the differences in the outcomes of therapeutic management of early esophageal carcinoma between different parts of the world may be explained by the number of cancers diagnosed at an early stage.Citation2
Currently, based on the preoperative chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) trial and the neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010), neoadjuvant chemoradiotherapy (nCRT) combined with esophagectomy has become the standard care for locally advanced esophageal cancer. The CROSS study was a multicenter trial from the Netherlands, where neoadjuvant chemoradiation resulted in increased median survival compared to the surgery-only group. This resulted in the consolidation of this approach in international practice and its widespread adoption.Citation3 The recently published 10-year follow-up of the CROSS trial indicates that neoadjuvant chemoradiotherapy plus surgery can still be regarded as a standard of care.Citation4 The NEOCRTEC5010 trial shows that neoadjuvant chemoradiotherapy (nCRT) plus surgery improves survival over surgery alone among patients with locally advanced ESCC, with acceptable and manageable adverse events.Citation5
Prognosis and survival in esophageal cancer have hinged on the lymph node status as the most important predictor. However, tumor regression grade (TRG) has been recently a topic of interest and is cited as a new prognostic indicator for cancers of the gastrointestinal tract including esophageal cancer.Citation6 TRG describes the histopathologic changes in response to neoadjuvant therapy. Five TRG systems have been described and proposed for use in esophageal cancer; however, none have become a standard grading system. They include the Mandard system; the Chirieac system; the Schneider system; the Hermann system; and the Japan Esophageal Society (JES) system.Citation7
In a recent studyCitation8 published in the Journal of Investigative Surgery (JIS), including patients with locally advanced esophageal cancer who underwent neoadjuvant chemoradiation therapy (nCRT) plus esophagectomy, the authors found that overall survival (OS) and disease-free survival (DFS) after nCRT could not be well stratified by TRG alone, but when stratified by nodal status, the pN + group had significantly worse overall and disease-free survival than the pN0 group. Univariate regression analysis showed that TRG significantly impacted overall survival and disease-free survival, however, on multivariate analysis, only the pN stage was the only independent prognostic factor and DFS in esophageal cancer after nCRT. The authors created a modified tumor regression grading system by incorporating both TRG and pathological nodal status. This system stratified survival curves well, and similar results were observed in DFS.
Esophageal cancer has a poor prognosis. While many systems proposed to predict prognosis in EC patients who received preoperative chemoradiotherapy, the modified TRG system proposed by Gu et al.Citation8 is an additional tool that may facilitate postoperative treatment decisions and survival surveillance of this challenging cancer. However, given the high percentage of SCC in this study, further studies specifically addressing patients with adenocarcinoma should be undertaken to determine if this grading system is applicable to that group of patients.
Disclosure statement
No potential conflict of interest was reported by the author(s).
References
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [published correction appears in CA Cancer J Clin. 2020 Jul;70(4):313]. CA Cancer J Clin. 2018;68(6):394–424. doi:10.3322/caac.21492
- Domper Arnal MJ, Ferrández Arenas Á, Lanas Arbeloa Á. Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol. 2015;21(26):7933–7943. doi:10.3748/wjg.v21.i26.7933.
- van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–2084. doi:10.1056/NEJMoa1112088
- Eyck BM, van Lanschot JJB, Hulshof MCCM, CROSS Study Group, et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: The randomized controlled CROSS trial. J Clin Oncol. 2021;39(18):1995–2004. doi:10.1200/JCO.20.03614.
- Yang H, Liu H, Chen Y, AME Thoracic Surgery Collaborative Group, et al. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010): A phase III multicenter, randomized, open-label clinical trial. J Clin Oncol. 2018;36(27):2796–2803. doi:10.1200/JCO.2018.79.1483.
- Xie JW, Lu J, Xu BB, et al. Prognostic value of tumor regression grading in patients treated with neoadjuvant chemotherapy plus surgery for gastric cancer. Front Oncol. 2021;11:587856. doi:10.3389/fonc.2021.587856.
- Lerttanatum N, Tharavej C, Chongpison Y, Sanpavat A. Comparison of tumor regression grading system in locally advanced esophageal squamous cell carcinoma after preoperative radio-chemotherapy to determine the most accurate system predicting prognosis. J Gastrointest Oncol. 2019;10(2):276–282. doi:10.21037/jgo.2018.12.01.
- Gu YM, Lyu SM, Shang QX, et al. Is tumor regression grade sufficient to predict survival in esophageal cancer with trimodal therapy?. J Invest Surg. 2022;35(11–12):1818–1823. doi:10.1080/08941939.2022.2127036.