An international cohort study of prognosis associated with pathologically complete response following neoadjuvant chemotherapy versus chemoradiotherapy of surgical treated esophageal adenocarcinoma

Objective: To compare overall (OS) and recurrence-free survival (RFS) in esophageal adenocarcinoma patients with a pathologically complete response (pCR) following neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT). Background: In the absence of survival differences in several prior studies comparing nCT with nCRT, the higher rate of pCR after nCRT has been suggested as reason to prefer this modality over nCT. Methods: An international cohort study included data from 8 high-volume centers. Inclusion criteria was patients with esophageal adenocarcinoma, between 2008 and 2018, who had a pCR after nCT or nCRT. Univariate analysis was used to compare demographic factors, and Kaplan-Meier survival analysis used to compare 5-year OS and RFS between groups. Results: In all, 465 patients with pCR following neoadjuvant treatment were included; 132 received nCT and 333 received nCRT. There was no statistically significant difference in 5-year OS between groups (78.8% (nCT) vs 65.5% (nCRT), P = 0.099), with a similar result demonstrated in multivariate analysis (HR = 1.19, 95% CI 0.77–1.84). 5-year RFS was significantly reduced in patients with a pCR following neoadjuvant chemoradiotherapy (75.3% (nCRT) vs 87.1% (nCT), P = 0.026). Multivariate analysis confirmed nCRT was associated with a poorer 5-year RFS (HR = 1.70, 95% CI 1.22–2.99). nCRT associated with a significantly greater prevalence of 5-year distant recurrence (odds ratio = 2.50, 95% CI 1.25–4.99) Conclusions: The results of this international cohort study show that the prognosis of pCR following different neoadjuvant regimes differs, bringing into question the validity of this measure as an oncological surrogate when comparing neoadjuvant treatment schemes for esophageal adenocarcinoma.