Clinical Impact of Remnant Lymphatic Invasion on The Recurrence of Esophageal Squamous Cell Carcinoma After Esophagectomy with Neoadjuvant Chemotherapy: A Retrospective Study

Abstract

Background: For stage II and III esophageal squamous cell carcinoma (ESCC), neoadjuvant chemotherapy (NAC) followed by esophagectomy is recommended in Japanese guidelines. However, recurrence of ESCC is common regardless of the NAC regimen and operation method, and the effect of NAC on recurrence is limited.Methods: We retrospectively analyzed the outcomes of 54 patients who underwent esophagectomy for ESCC after NAC from 2010 to 2017. We selected 53 patients with ESCC without NAC followed by esophagectomy from 2001 to 2017 for comparison.Results: Among patients who underwent NAC followed by surgery, lymphatic invasion (ly) (hazard ratio: 2.632; 95% CI: 1.04–6.68, p = 0.042) and microscopic residual tumor (R) (hazard ratio: 24.21, 95% CI: 1.92–305, p = 0.014) were independent factors significantly associated with 3-year recurrence-free survival in patients with esophagectomy after NAC in multivariate analysis. In patients without ly after NAC, the presence of lymph node metastasis in pathological diagnosis (pN) was not significantly related to recurrence (p = 0.2401). Recurrence was significantly related to ly (+) (p = 0.0024) in the group with pN after NAC. There were significantly fewer ly (+) patients in the NAC (+) group (p = 0.0332) than those in the NAC (-) group.Conclusion: The presence of ly was an independent risk factor for recurrence of ESCC after esophagectomy following NAC. pN was not a significant recurrence factor for cases with esophagectomy following NAC in multivariate analysis. Adjuvant treatment after surgery may be required in cases with remnant ly after NAC.

Impacts of tumor microenvironment during neoadjuvant chemotherapy in patients with esophageal squamous cell carcinoma

“…Recent studies have suggested the positive effects of NAC on antitumor immunity in EC patients. 16,17 Other investigations showed tumor-infiltrating lymphocytes to be decreased after NAC in gastroesophageal malignancies 31 and breast cancer. 32,33 Our finding that numerous immune components significantly decreased after NAC is in line with a recent study that showed residual tumors after NAC to be immune suppressed.…”

“…[12][13][14] The TME status and its associations with clinical outcomes have been evaluated mainly in ESCC patients not receiving NAC. 15 Recent studies have examined the effects of NAC on TME in ESCC, [16][17][18] and highlighted the impacts of tumor-infiltrating lymphocytes and PD-L1 expression on the clinical outcomes of ESCC patients receiving NAC followed by surgery. 18,19 The clinical impacts of various TME components have yet to be investigated in ESCC patients receiving NAC, and no studies have addressed whether changes in TME status after versus before NAC are associated with the clinical outcomes of ESCC patients.…”