Validity of upfront surgery for patients with unsuspected lymph node metastasis in esophageal cancer: a propensity scoring matching study

BACKGROUND: Although neoadjuvant therapy followed by esophagectomy is well-established as being superior to upfront esophagectomy when locoregional lymph node (LN) metastasis is present in esophageal cancer, upfront esophagectomy without neoadjuvant therapy may be performed in patients with LN metastasis due to unreliable preoperative evaluations. However, outcomes in this setting remain unclear. The purpose of the present study was to clarify whether upfront esophagectomy without neoadjuvant therapy in patients with unsuspected lymph node metastasis in esophageal cancer is appropriate. METHODS: We included 215 squamous cell esophageal cancer patients who met the study criteria. Inclusion criteria included complete (R0) and curative surgery cases, intra-thoracic esophageal cancer, preoperative biopsy-proven squamous cell carcinoma, and cases without LN metastasis (WL, cN0 and pN0) or with unsuspected LN metastasis (UL, cN0 and pN1). Exclusion criteria were palliation or salvage cases, other uncured previous or current primary cancers, complete remission cases, and operative mortalities (defined as patients who died during hospitalization or within one month after surgery). We compared 5-year disease- free survival (DFS) between WL and UL. In addition, we investigated the influence of neoadjuvant therapy in UL. To overcome heterogeneity in baseline characteristics between the groups, a propensity matched-analysis based on propensity scores was then carried out to create a cohort of WL with clinical characteristics similar to those in UL. RESULTS: The incidence of UL among preoperative N0 patients was 25.6% and the incidence of UL cases who did not receive neoadjuvant therapy was 47.2%. All subjects were stratified into either WL (160 patients) or UL (55 patients). Twenty nine of 55 patients in UL received neoadjuvant therapy before esophagectomy and all patients with LN metastasis received adjuvant therapy after esophagectomy. There was no significant difference in DFS between WL and UL (p = 0.242). Furthermore, there were no significant differences in DFS between cases that received and did not receive neoadjuvant therapy (p = 0.769). CONCLUSIONS: Upfront surgery without neoadjuvant therapy in UL is appropriate for patients who can tolerate adjuvant therapy.