LVI is a common pathological manifestation of tumor cells invading blood and lymphatic vessels. It exists in the postoperative specimens of various malignant tumors. LVI is an important risk factor affecting the prognosis of cancer patients. It has been reported in non-small cell lung cancer, colorectal cancer, gastric cancer, and other malignant tumors[15–18]. Because it can accurately predict the prognosis of patients with hepatocellular carcinoma, LVI has become a reliable indicator for staging and prognosis of hepatocellular carcinoma[19]. Yu et al. showed that LVI is an independent risk factor affecting the prognosis of ESCC patients without LNM[10]. Other studies showed that ESCC patients with LVI were more likely to have LNM, and LVI strongly correlated with reduced RFS[20–22]. In the present study, the 5-year OS rate was 40.9% and 41.6% in the AC and NC groups, respectively, which were lower than the 5-year OS rate of lymph node-negative (pN0) ESCC patients (75.6% vs 69.7% in the postoperative treatment and surgery alone groups, respectively)[23]. Bone metastasis and local LNM were the most common recurrence patterns, which are consistent with findings from previous studies[24].
Various treatment strategies have been used in perioperative adjuvant therapy for ESCC[25–27]. At present, a consensus has been reached that esophageal carcinoma patients with positive lymph nodes can benefit from neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy[28, 29]. However, the adjuvant therapy for ESCC remains controversial[30, 31]. Based on the results of the Japan Clinical Oncology Group (JCOG) 9204 trial, the guidelines of the Japanese Esophageal Society suggest that POAC can be administered to ESCC patients with positive lymph nodes. The National Comprehensive Cancer Network (NCCN) guidelines suggest that patients with R0 resection cannot receive adjuvant treatment regardless of the T stage and N stage, and those without R0 resection can receive postoperative chemoradiotherapy or palliative treatment. However, the guidelines of the European Society of Medical Oncology and the Chinese Society of Clinical Oncology have not yet given clear opinions on the adjuvant treatment for ESCC after surgery. Postoperative chemoradiotherapy and postoperative chemotherapy have relatively comparable effects. Some clinical studies found that postoperative adjuvant therapy can still be beneficial even for ESCC patients with negative lymph nodes[5]. Tetsuro et al. pointed out that ESCC patients with LVI and negative lymph nodes may benefit from postoperative chemotherapy[7]. However, all ESCC patients with LVI and negative lymph nodes in their study did not receive postoperative chemotherapy. Our study found no significant difference in the 5-year OS rate between the AC group and the NC group. Moreover, no statistical difference in RFS was found between the two groups. Subgroup analysis also showed that even though the 5-year OS rate of patients in the AC group was significantly better than that of patients in the NC group (75% vs. 40%), no statistical difference was observed. No statistical difference was found between the two groups in the 5-year OS rate for patients with stages IIA (35.7% vs. 54.5%) and IIB (25.0% vs. 25.0%). In addition, univariate and multivariate analyses further showed that the 5-year OS rate of patients was not affected by the postoperative treatment strategy. This may be because chemotherapy sometimes leads to severe adverse events and would be harmful[5, 27, 32]. It may also be related to the great trauma caused by surgery, resulting in poor tolerance of postoperative treatment. Among the patients receiving adjuvant treatment after surgery, 3 switched to oral chemotherapy because of the side effects of intravenous chemotherapy. Another patient died due to the side effects of chemotherapy.
For patients who developed esophageal cancer post-operation, the recurrence pattern could be divided into local recurrence and distant metastasis. Studies have shown that most patients with ESCC recurred within 3 years after surgery[24, 33]. Local recurrence after surgery is the main recurrence mode for patients with negative lymph nodes. In our study, 22 (81.5%) patients died of postoperative recurrence, including 8 (36.4%) patients with local recurrence and 13 (59.1%) patients with distant metastasis. Distant metastasis was the main recurrence mode of these patients, which is much higher than the results of similar studies[24, 34, 35]. Maehara et al. found that the level of vascular endothelial growth factor (VEGF) in tumor tissue of patients with LVI was higher. Both the depth of invasion and the vessel system in the tumor tissue increased with the growth of the tumor. Angiogenesis promoted tumor formation by secreting VEGF, which allows tumor cells to invade the vessel system due to the incomplete basement membrane[36]. This may explain why patients with LVI are more likely to develop distant metastasis after surgery. In addition, 6 (27.3%) of the patients with recurrence had bone metastasis, which accounted for the highest proportion in all recurrence patterns. In many diagnosis and treatment guidelines, the exclusion of bone metastasis is not a routine item of preoperative staging and postoperative reexamination, and therefore the value of excluding bone metastasis should be reassessed.
Nonetheless, this study has some limitations. In this retrospective study, different doctors had different bases when choosing treatment plans for patients. In addition, the postoperative recovery status of patients was not completely the same, and the auxiliary treatment plans were not completely the same. There was selection bias. For example, patients with postoperative pathological stage T3 did not receive preoperative neoadjuvant therapy, partly because the results of preoperative ultrasonic gastroscopy were inconsistent with postoperative pathological results, and the patients were subjectively unwilling to receive preoperative neoadjuvant therapy. The proportion of thoracoscopic surgery was significantly higher in the AC group, which may be linked to the small incision of thoracoscopic surgery, the good postoperative recovery of patients, and their willingness to accept postoperative adjuvant treatment. In addition, the number of enrolled patients is small, hence the research results are not conclusive. During follow-up, the causes of death of some patients could not be investigated very accurately due to limited medical equipment. Future studies should be conducted with a larger sample of prospective clinical control studies to validate these results.