P1.066. Prognostic Equivalence of ypN and pN Staging in Esophageal Cancer After Neoadjuvant Therapy: A Multicenter Cohort Study of 2,545 Patients
TL;DR
Findings challenge the unconditional interchangeability of ypN and pN in current staging systems and have direct implications for adjuvant treatment decision-making after neoadjuvant esophageal cancer therapy.
Abstract
Esophageal Cancer: Surgical Treatment of Esophageal Cancer Current staging systems apply ypN and pN categories interchangeably after neoadjuvant therapy plus esophagectomy; however, their prognostic equivalence has not been rigorously established. We investigated whether ypN0–3 confers equivalent disease-free survival (DFS) to pN0–3. We analyzed 2,545 consecutive esophagectomy patients from three high-volume centers with complete DFS data. Patients were stratified by treatment type—neoadjuvant therapy followed by surgery (ypN group, n = 1,060) vs. upfront surgery (pN group, n = 1,485)—and by N category (N0–N3). Analyses included Kaplan–Meier estimation, multivariable Cox proportional-hazards regression with interaction testing (N_stage × treatment type), propensity score matching (PSM), and restricted mean survival time (RMST) equivalence testing at 60 months (pre-specified margin: ±6 months). The N_stage × treatment-type interaction was statistically significant (p < 0.01), indicating N-category–dependent equivalence. ypN1 vs. pN1: HR 1.06 (95% CI, 0.89–1.27; p = 0.49), ΔRMST = −1.1 months (equivalent). ypN3 vs. pN3: HR 1.29 (95% CI, 0.87–1.93; p = 0.20), ΔRMST = −2.3 months (equivalent). In contrast, ypN0 conferred significantly inferior DFS vs. pN0 (HR 1.23, 95% CI 1.06–1.42; p = 0.005), and ypN2 diverged most markedly from pN2 (HR 1.56, 95% CI 1.19–2.05; p = 0.001; ΔRMST = −6.7 months, exceeding the equivalence margin). PSM-adjusted analyses confirmed all findings. ypN and pN staging are not universally prognostically equivalent. ypN1 and ypN3 appear equivalent to their pN counterparts, whereas ypN0 and particularly ypN2 carry worse prognoses than corresponding pN stages. These findings challenge the unconditional interchangeability of ypN and pN in current staging systems and have direct implications for adjuvant treatment decision-making after neoadjuvant esophageal cancer therapy.