NCRT is the standard treatment strategy for advanced esophageal cancer, and PT is also an important treatment for esophageal cancer. Currently, it is not clear whether esophageal cancer (EC) patients who receive NCRT and esophagectomy need further postoperative chemoradiotherapy. Therefore, it is worth assessing whether conducting a PT after NCRT improves the OS of resected EC patients. However, there are no published RCTs that address this question.
In esophagogastric cancer, evidence has demonstrated that patients treated with both neoadjuvant and PT could have a significantly improved OS than patients who do not receive PT. However, the patients received neoadjuvant chemotherapy (not NCRT), and the present study has explored gastric and gastroesophageal junction carcinomas.13–15
Samson et al. retrospectively analyzed 3100 patients with pathologic positive nodes (ypN+) after neoadjuvant therapy and esophagectomy. Out of these, 2625 patients (84.7%) did not receive postoperative chemotherapy, while the remaining 475 patients (15.3%) did. The OS of ypN + stage patients who received postoperative chemotherapy was significantly improved. Therefore, postoperative chemotherapy was shown to be independently associated with decreased mortality hazard (HR = 0.69, 95% CI 0.57–0.83, P < 0.001). More than 80% of the patients in the study had a pathological adenocarcinoma. Of the patients receiving neoadjuvant therapy alone, 2279 (86.8%) received neoadjuvant chemoradiotherapy while only 346 (13.2%) received neoadjuvant chemotherapy. Among the patients receiving neoadjuvant therapy combined with PT, 344 (72.4%) received neoadjuvant chemoradiotherapy, while 131 (27.6%) received neoadjuvant chemotherapy.16 Our results show that PT may improve the survival of positive lymph node patients after neoadjuvant chemoradiotherapy and resection for EC, especially esophageal adenocarcinoma.
This meta-analysis included seven retrospective cohort studies.6–12 The pathological type of the subjects in the studies by Mookdad and Drake was esophageal adenocarcinoma.10, 12 Meanwhile, the study subjects of Burt were mainly esophageal adenocarcinoma, mixed with a few squamous cell carcinomas.7 However, the study by Burt has independent survival data of esophageal adenocarcinoma in the subgroup analysis, and the survival status of esophageal adenocarcinoma could be extracted separately. The most prevalent pathological type among the subjects of the four included studies was adenocarcinoma (≥ 80%), and squamous cell carcinoma (༜20%). However, the survival status of adenocarcinoma patients could not be extracted from the original text.
The ypN + lymph node status of patients after neoadjuvant chemoradiotherapy is directly correlated to a poor prognosis, while ypN0 has an inverse correlation.17 Burt et al. separately analyzed the survival of patients depending on the lymph node status, with the postoperative staging of ypN0 and ypN+. 7 However, Brescia et al and Drake et al only included patients with postoperative ypN + .6, 12 Christopher et al. conducted separate survival analysis on patients under four conditions according to the different preoperative clinical staging (ycN)/ postoperative lymph node pathological staging [(ypN),: ycN + / ypN +, ycN + / ypN0, ycN0 / ypN +, and ycN0 / ypN0].The other studies have did not distinguish between the lymph node status (ypN0 or ypN+).11 We further analyzed the survival of patients with esophageal cancer according to the different states of ypN0 and ypN+. The analysis results showed that PT might not significantly improve the OS of resected EC patients who received NCRT and had the ypN0 pathological staging. Although we showed that the NCRT + PT group have a similar or even higher ypN + patients’ ratio with NCRT alone (see Table 1), the NCRT + PT group generally had a better OS. It also indirectly suggests that PT could improve the prognosis of EC patients with ypN +.
Several limitations of this meta-analysis need to be considered with caution. First, all the studies included were retrospective cohort researches. Second, the chemotherapy and radiotherapy regimens of NCRT in the various studies were not similar, and some of the studies have not detailed the PT regimens followed. Third, almost all the patients included in the meta-analysis had esophageal adenocarcinoma. Therefore, our conclusion may only apply to esophageal adenocarcinoma cases.
In conclusion, PT may improve the survival of NCRT patients with resected esophageal cancer. However, subgroup analysis showed administration of PT to ypN0 patients did not improve the OS, while the OS of ypN + patients was improved after receiving PT. Considering that the study included an absolute advantage for adenocarcinoma patients. This conclusion may be more applicable to EAC patients treated with NCRT at the ypN + stage. Combined with the current NCCN guidelines, it could be necessary to procure PT for lymph node-positive esophageal adenocarcinoma patients who undergo NCRT combined with surgery. Considering that the researches we included are all retrospective studies, this conclusion should be confirmed by further high-level prospective studies.