Benefits of neoadjuvant chemotherapy: is the prognosis of ypN0 patients after neoadjuvant chemotherapy comparable to that of pN0 patients undergoing surgery alone?

Background: Preoperative treatment has become widely recognized for improving survival in patients with esophageal cancer. The present study aimed to compare the prognosis between patients with pathological node-negative status treated with surgery alone (SA-pN0) and those who were clinically node-positive but converted to ypN0 following neoadjuvant chemotherapy (NAC-ypN0) in cases of advanced thoracic esophageal squamous cell carcinoma (ESCC).

Methods: This retrospective analysis used a multicenter database of 4849 consecutive patients who underwent treatment for esophageal cancer. Patients with clinical T2 or more advanced ESCC who underwent standard subtotal esophagectomy between 1990 and 2017 were included. The NAC-ypN0 group was compared with the SA-pN0 group in terms of patient characteristics, recurrence patterns, and survival outcomes using propensity score-matched analysis.

Results: In total, 109 patients were classified as NAC-ypN0 and 137 as SA-pN0. Propensity score matching resulted in the selection of 87 patients per group. Compared with the SA-pN0 group, the NAC-ypN0 group had a significantly more advanced clinical TNM stage and underwent significantly more three-field lymphadenectomies. Pathological findings showed downstaging of the pT stage in the NAC-ypN0 group, resulting in an equivalent distribution between the two groups. Additionally, the NAC-ypN0 group had significantly lower rates of lymphatic invasion (33% vs. 56%) and venous invasion (21% vs. 52%). Recurrence rates (21% vs. 22%) and survival outcomes (5-year overall survival: 83.9% vs. 76.1%, P = 0.110) were comparable between the two groups.

Conclusions: The NAC-ypN0 group demonstrated reduced lymphovascular invasion and showed a prognosis comparable to that of the SA-pN0 group.