Neoadjuvant Chemoradiotherapy with Cisplatin Plus Fluorouracil for Borderline Resectable Esophageal Squamous Cell Carcinoma


Neoadjuvant Chemoradiotherapy with Cisplatin Plus Fluorouracil for Borderline Resectable Esophageal Squamous Cell Carcinoma


Takeshi Suzuki MD, Akihiko Okamura MD, PhD, Masayuki Watanabe MD, PhD, Shinji Mine MD, PhD, Yu Imamura MD, PhD, Takao Asari MD, Hiroki Osumi MD, Izuma Nakayama MD, PhD, Takashi Ichimura MD, PhD, Mariko Ogura MD, Akira Ooki MD, PhD, Daisuke Takahari MD, PhD, Kensei Yamaguchi MD & Keisho Chin MD 



The optimal treatment strategy for patients with borderline resectable (BR) esophageal squamous cell carcinoma (ESCC), in which tumors grow very close to the adjacent vital organs, remains unclear. This study evaluated the efficacy of neoadjuvant chemoradiotherapy (NACRT) with cisplatin plus fluorouracil (CF) and irradiation (40 Gy) for these patients.


The study cohort included 50 patients with BR-ESCC who received NACRT as the initial treatment and were allocated to one of two groups: patients who achieved curative resection (R0 group) or those who did not (Non-R0 group). The overall survival (OS), relapse-free survival (RFS), and pre-therapeutic predictive factors for Non-R0 were evaluated.


Among the 50 patients, 22 (44%) achieved curative resection clinically. The median OS was significantly better in the R0 group than in the Non-R0 group (2.4 vs 0.8 years; hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.12–0.67; p < 0.01). The independent predictive factors before NACRT for Non-R0 were higher serum SCC antigen level (p < 0.01) and clinical nodal involvement (p = 0.02). In addition, OS was significantly worse for the patients with higher levels of serum SCC antigen than for those with lower levels (p < 0.01).


Curative resection was achieved for about 40% of the patients who received NACRT for BR-ESCC. Therefore, NACRT could be a useful neoadjuvant treatment option for BR-ESCC. However, a higher serum SCC antigen level before NACRT is predictive of treatment failure and poor survival.

Esophageal cancer is the eighth leading cause of death worldwide,1 and regardless of recent therapeutic advances, the survival rate after diagnosis was only 19.9% during the first half of 2019 in the United States.2 For more than 70% of such cases, the diagnosis is esophageal squamous cell carcinoma (ESCC), and most cases occur in Asian countries.3

In Japan, the standard therapy for stages 2 and 3 ESCC is neoadjuvant chemotherapy (NAC) with cisplatin plus 5-fluorouracil (CF) followed by surgery,4,5 whereas the treatment for unresectable T4b ESCC is definitive chemoradiotherapy (CRT).6,7,8,9 However, in clinical practice, borderline resectable (BR) cases with suspected tumor invasion of adjacent organs are sometimes encountered, but the definitive diagnosis in these cases is not T4b disease. Although the JCOG9907 study showed the survival benefit of NAC-CF over postoperative CF for cStages 2 and 3 ESCC, NAC-CF was not sufficient to improve the survival of patients with cT3 tumors,4 suggesting that NAC with CF might be insufficient for BR-ESCC patients. Therefore, a more powerful neoadjuvant regimen is required to improve survival. However, limited data are available regarding alternative treatment options for BR-ESCC.

Neoadjuvant chemoradiotherapy (NACRT) is a prevalent treatment option for esophageal cancer worldwide, and several previous studies have reported the superiority of NACRT over surgery alone.10,11,12,13,14 However, because these reports enrolled patients with definitely resectable disease, the efficacy of NACRT with CF or other regimens for patients with BR-ESCC is unclear.

Therefore, the current study aimed to investigate the treatment results of NACRT with CF and 40 Gy of irradiation for BR-ESCC and to identify the pre-therapeutic clinical factors affecting the curative resection rate and survival.

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Year 2020
Language English
Format PDF
DOI 10.1245/s10434-019-08124-x