Impact of High Immunoreactivity on Surgically Treated Serum p53 Antibody-Positive Esophageal Squamous Cell Carcinoma after Neoadjuvant Therapy: A Multi-Institutional Study of 637 Cases.

PURPOSE: This multi-institutional study investigated the clinical and prognostic significance of serum p53 antibody (s-p53-Ab) titers in patients with s-p53-Ab-positive esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemotherapy (NAC). METHODS: We analyzed 637 patients who underwent surgery at 15 institutions. Patients were divided into upfront surgery (n = 375) and NAC (n = 262) groups and stratified into high-titer (≥9.82 ng/mL) and low-titer (>1.30 to <9.82 ng/mL) groups. RESULTS: In the upfront surgery group, high-titer patients had significantly worse relapse-free survival (P = 0.046) and overall survival (P = 0.024) than low-titer patients. In contrast, no significant survival differences were observed by titer after NAC, and the poorer prognosis associated with high s-p53-Ab titers in the upfront surgery cohort was not seen after NAC. Subgroup analyses of stage II and III disease showed similar, nonsignificant trends toward improved outcomes in high-titer patients after NAC. CONCLUSIONS: These findings suggest that high s-p53-Ab titers are associated with a poor prognosis in patients undergoing upfront surgery. Although these observations did not reach statistical significance, patients with high titers may potentially benefit from NAC, indicating its potential therapeutic value in those with a strong p53 antibody response.