A New Choice of Treatments for Invasive Superficial Esophageal Squamous Cell Carcinoma: Investigation of Efficacy of Prophylactic Chemoradiation Therapy After Endoscopic Submucosal Dissection

Abstract

Purpose/Objective(s)In Japan, endoscopic submucosal dissection (ESD) is becoming a common procedure for superficial esophageal squamous cell carcinoma that is shallower than the muscularis mucosa. However, if the invasion is deeper than muscularis mucosa, the risk of lymph node metastasis is reportedly as high as 15% to 60%. The aim of this study was to evaluate the efficacy and the adverse events of prophylactic chemoradiation therapy after ESD for these populations.Materials/MethodsTreatment outcomes of 47 patients with superficial esophageal cancer that invaded deeper than the lamina propria mucosa who received radiation therapy between October 2000 and December 2011 were retrospectively reviewed. Among them, sixteen patients with invasion into the submucosal layer or the muscularis mucosa with positive vascular invasion were treated with prophylactic chemoradiation therapy (CRT) using 5-FU with/without cisplatin after ESD (ESD-CRT-group). The remaining 31 patients were treated with CRT only (CRT-alone-group). In the ESD-CRT group, radiation was given to the prophylactic lymph node area with 40 Gy in 20 fractions in 15 patients and 44 Gy in 22 fractions in one patient. Six of them received a boost radiation to a total dose of 60 Gy for PET-positive lymph nodes (4 patients) or positive margins (2 patients). The total dose of the CRT-alone group ranged from 54 to 69.4 Gy (median, 66 Gy). Kaplan-Meier curves and the log-rank test were used for analysis. The median follow-up periods of the ESD-CRT group and CRT-alone group were 39.0 months and 34.2 months, respectively (p = 0.68).ResultsTumor recurrence developed in 8 patients (25.8%) in the CRT-alone group and 1 (6.3%) in the ESD-CRT group (Fisher exact test, p = 0.107). Of note, local tumor recurrence was observed in 6 patients (19%) in the CRT-alone group and none in the ESD-CRT group although the difference was not statistically significant (Fisher exact test, p = 0.069). The 3-year overall survival rates in the CRT-alone group and the ESD-CRT group were estimated to be 63.2% and 90.0% (p = 0.12), while the 3-year progression-free survival rates in these two groups were 74.1% and 90.0%, respectively (p = 0.34). Grade 3 esophageal stricture appeared in 4 patients (25%) in the ESD-CRT group and 1 patient (3%) in the CRT-alone group (p < 0.00009). There were no significant differences in other acute and late toxicities between the two groups.ConclusionsDespite limitations because of the retrospective nature of this study, these results suggest that prophylactic CRT after ESD is a safe and effective approach for superficial esophageal squamous cell carcinomas. Especially in cases in which submucosal invasion is suspected, this combination strategy might be more effective than CRT alone. Purpose/Objective(s)In Japan, endoscopic submucosal dissection (ESD) is becoming a common procedure for superficial esophageal squamous cell carcinoma that is shallower than the muscularis mucosa. However, if the invasion is deeper than muscularis mucosa, the risk of lymph node metastasis is reportedly as high as 15% to 60%. The aim of this study was to evaluate the efficacy and the adverse events of prophylactic chemoradiation therapy after ESD for these populations. In Japan, endoscopic submucosal dissection (ESD) is becoming a common procedure for superficial esophageal squamous cell carcinoma that is shallower than the muscularis mucosa. However, if the invasion is deeper than muscularis mucosa, the risk of lymph node metastasis is reportedly as high as 15% to 60%. The aim of this study was to evaluate the efficacy and the adverse events of prophylactic chemoradiation therapy after ESD for these populations. Materials/MethodsTreatment outcomes of 47 patients with superficial esophageal cancer that invaded deeper than the lamina propria mucosa who received radiation therapy between October 2000 and December 2011 were retrospectively reviewed. Among them, sixteen patients with invasion into the submucosal layer or the muscularis mucosa with positive vascular invasion were treated with prophylactic chemoradiation therapy (CRT) using 5-FU with/without cisplatin after ESD (ESD-CRT-group). The remaining 31 patients were treated with CRT only (CRT-alone-group). In the ESD-CRT group, radiation was given to the prophylactic lymph node area with 40 Gy in 20 fractions in 15 patients and 44 Gy in 22 fractions in one patient. Six of them received a boost radiation to a total dose of 60 Gy for PET-positive lymph nodes (4 patients) or positive margins (2 patients). The total dose of the CRT-alone group ranged from 54 to 69.4 Gy (median, 66 Gy). Kaplan-Meier curves and the log-rank test were used for analysis. The median follow-up periods of the ESD-CRT group and CRT-alone group were 39.0 months and 34.2 months, respectively (p = 0.68). Treatment outcomes of 47 patients with superficial esophageal cancer that invaded deeper than the lamina propria mucosa who received radiation therapy between October 2000 and December 2011 were retrospectively reviewed. Among them, sixteen patients with invasion into the submucosal layer or the muscularis mucosa with positive vascular invasion were treated with prophylactic chemoradiation therapy (CRT) using 5-FU with/without cisplatin after ESD (ESD-CRT-group). The remaining 31 patients were treated with CRT only (CRT-alone-group). In the ESD-CRT group, radiation was given to the prophylactic lymph node area with 40 Gy in 20 fractions in 15 patients and 44 Gy in 22 fractions in one patient. Six of them received a boost radiation to a total dose of 60 Gy for PET-positive lymph nodes (4 patients) or positive margins (2 patients). The total dose of the CRT-alone group ranged from 54 to 69.4 Gy (median, 66 Gy). Kaplan-Meier curves and the log-rank test were used for analysis. The median follow-up periods of the ESD-CRT group and CRT-alone group were 39.0 months and 34.2 months, respectively (p = 0.68). ResultsTumor recurrence developed in 8 patients (25.8%) in the CRT-alone group and 1 (6.3%) in the ESD-CRT group (Fisher exact test, p = 0.107). Of note, local tumor recurrence was observed in 6 patients (19%) in the CRT-alone group and none in the ESD-CRT group although the difference was not statistically significant (Fisher exact test, p = 0.069). The 3-year overall survival rates in the CRT-alone group and the ESD-CRT group were estimated to be 63.2% and 90.0% (p = 0.12), while the 3-year progression-free survival rates in these two groups were 74.1% and 90.0%, respectively (p = 0.34). Grade 3 esophageal stricture appeared in 4 patients (25%) in the ESD-CRT group and 1 patient (3%) in the CRT-alone group (p < 0.00009). There were no significant differences in other acute and late toxicities between the two groups. Tumor recurrence developed in 8 patients (25.8%) in the CRT-alone group and 1 (6.3%) in the ESD-CRT group (Fisher exact test, p = 0.107). Of note, local tumor recurrence was observed in 6 patients (19%) in the CRT-alone group and none in the ESD-CRT group although the difference was not statistically significant (Fisher exact test, p = 0.069). The 3-year overall survival rates in the CRT-alone group and the ESD-CRT group were estimated to be 63.2% and 90.0% (p = 0.12), while the 3-year progression-free survival rates in these two groups were 74.1% and 90.0%, respectively (p = 0.34). Grade 3 esophageal stricture appeared in 4 patients (25%) in the ESD-CRT group and 1 patient (3%) in the CRT-alone group (p < 0.00009). There were no significant differences in other acute and late toxicities between the two groups. ConclusionsDespite limitations because of the retrospective nature of this study, these results suggest that prophylactic CRT after ESD is a safe and effective approach for superficial esophageal squamous cell carcinomas. Especially in cases in which submucosal invasion is suspected, this combination strategy might be more effective than CRT alone. Despite limitations because of the retrospective nature of this study, these results suggest that prophylactic CRT after ESD is a safe and effective approach for superficial esophageal squamous cell carcinomas. Especially in cases in which submucosal invasion is suspected, this combination strategy might be more effective than CRT alone.