Regarding “Final Analysis of Diagnostic Endoscopic Resection Followed by Selective Chemoradiotherapy for Stage I Esophageal Cancer: JCOG0508”

Abstract

We read with great interest the article by Nihei et al1Nihei N. et al.Gastroenterology. 2022; Google Scholar on the effective treatment strategy combining endoscopic resection (ER) and chemoradiation therapy (CRT) for stage I esophageal cancer. They found that the progression-free survival and overall survival of patients receiving ER followed by prophylactic CRT with 41.4 Gy for pathologic T1a (M) esophageal cancer with lymphovascular invasion or T1b (SM) esophageal cancer without vertical margins were equal to those of all enrolled patients with stage I esophageal cancer. We appreciate this treatment option for early esophageal cancer that avoids invasive surgical treatment and allows for esophageal preservation. However, a few patients in their study developed recurrence in the locoregional lymph nodes within the irradiated area, and salvage surgery was insufficient for these patients. The authors suggested the indication of surgery for these patients with lymphovascular invasion or insufficient chemotherapy. We would like to know if there is a possibility for further improvement of prophylactic CRT regimens in response to the present result. Prophylactic CRT with a radiation dose of 41.4 Gy may be insufficient to control potential lymph node metastases. Several studies reported a potential lymph node metastasis risk of 20%–40% in patients with T1a (M3)-T1b (SM) esophageal cancer.2Kodama M. et al.Surgery. 1998; 123: 432-439Abstract Full Text Full Text PDF PubMed Scopus (381) Google Scholar,3Kim D.J. et al.J Gastroenterol Hepatol. 2008; 23: 619-625Crossref PubMed Scopus (74) Google Scholar Indeed, 9 of 83 patients (11%) with T1a (M3)-T1b (SM) disease who underwent prophylactic CRT developed locoregional lymph node recurrence within a median of 16.4 months after treatment in this study. These results suggest that this prophylactic CRT regimen may not adequately prevent lymph node metastasis. Because distant metastasis was rare in this study, it is likely that the dose of local prophylactic radiotherapy was insufficient rather than the dose of systemic chemotherapy. In a previous report4Christophe M. et al.J Clin Oncol. 2014; 32: 2416-2422Crossref Scopus (416) Google Scholar of neoadjuvant CRT with a radiation dose of 45 Gy/25 fractions combined with cisplatin and 5-fluorouracil, the pathologic nodal status (pN) at surgery after neoadjuvant CRT was poorer than the clinical nodal status (cN) evaluated by computed tomography before treatment (cN0/1/2/3 = 69/29/0/0 in 98 patients vs pN0/1/2/3 = 56/15/8/2 in 81 patients, respectively). Of the 98 patients, 18 patients who underwent neoadjuvant CRT did not undergo surgery, suggesting that neoadjuvant CRT of approximately 40 Gy may be insufficient to control potential lymph node metastases. To strongly control potential regional lymph node metastases, doses higher than 41.4 Gy, such as 50 Gy or more, as is generally used in definitive CRT, may be effective. The relationship between the site of locoregional lymph node recurrence in the irradiation field and the site of the esophageal cancer was not described in detail in this study. If these locoregional lymph node recurrences were common in the area near the primary esophageal cancer, we could improve the local control rate by boosting irradiation with the definitive dose to the esophageal cancer area even in cases with a negative margin after ER. The authors considered that surgery may be better than CRT as an adjuvant treatment after ER in SM cases with lymphovascular invasion. However, the JCOG0502 trial tested the efficacy of definitive CRT as initial therapy without ER for T1bN0M0 esophageal cancer and found no significant difference in the 5-year overall survival between patients receiving surgery and those receiving CRT.5Ken K. et al.Gastroenterology. 2021; 161: 1878-1886Abstract Full Text Full Text PDF Scopus (22) Google Scholar Cisplatin and 5-fluorouracil were used as systemic chemotherapy in both JCOG0508 and JCOG0502, whereas JCOG0508 administered 41.4 Gy to the prophylactic lymph node area and JCOG0508 administered 60 Gy only to the area 2 cm craniocaudal of the main esophageal lesion and did not include the prophylactic lymph node area. We believe that it may be important to administer a sufficient dose of radiation to the lymphatic area near the esophageal cancer in patients in whom the risk of lymph node metastasis is presumed to be high. We again appreciate the authors’ effort toward revealing the usefulness of less-invasive prophylactic CRT as a treatment option for stage I esophageal cancer.