An International Cohort Study of Prognosis Associated With Pathologically Complete Response Following Neoadjuvant Chemotherapy Versus Chemoradiotherapy of Surgical Treated Esophageal Adenocarcinoma

Abstract

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.

Neoadjuvant Chemoradiotherapy Versus Chemotherapy for the Treatment of Locally Advanced Esophageal Adenocarcinoma in the European Multicenter ENSURE Study

“…The subgroup analysis of operative approach may also support this hypothesis, with the direction of effect favoring improved outcomes among patients post transthoracic esophagectomy treated with nCT. Moreover, in patients achieving an R0 resection, OS was significantly improved following nCT as compared with nCRT (HR = 2.61), consistent with a recent multicenter observational data from Cools-Lartigue et al, 12 who demonstrated that 5-year recurrence-free survival was significantly improved in those who achieved pCR following nCT as compared with nCRT (HR = 1.70), with concomitant reductions in systemic recurrence (OR = 2.50). These data in a large population, we suggest, can inform modern multidisciplinary team decision-making, supporting a context-dependent tailored approach in the choice of neoadjuvant strategy.…”

“…Intriguingly, it is suggested that a pCR following nCT has a more favorable long-term outcome as compared with those with a pCR following nCRT. This highlights the relevance of how an integrated response at both local and systemic sites gives the maximum oncologic benefit, with the increasing evidence of the efficacy of adjuvant immunotherapy in selected patients with LAEC supporting this thesis 12 …”

“…This highlights the relevance of how an integrated response at both local and systemic sites gives the maximum oncologic benefit, with the increasing evidence of the efficacy of adjuvant immunotherapy in selected patients with LAEC supporting this thesis. 12 ENSURE is an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers across 20 centers in Europe and North America which captured detailed baseline staging and treatment characteristics, perioperative outcomes, postoperative surveillance, recurrence patterns, treatment of recurrent disease, long-term oncologic outcomes, and health-related quality of life (HRQL). 13 The present study represents an a priori secondary analysis within the ENSURE study database, with the primary objective to determine the impact of neoadjuvant treatment on recurrence patterns and long-term oncologic outcomes and survival among patients with LAEC.…”

A phase 2 trial of peri-operative avelumab and chemotherapy for locally advanced gastro-esophageal adenocarcinoma: Association of AGR2/AP-1 complex CD8 T-cells and M2-Tumour Associated Macrophages with treatment response

“…Similarly, the mid-term survival outcomes described above are similar, if not marginally improved, to the outcomes described in other studies incorporating taxane based perioperative regimens 4,5 . Anecdotally, the overall survival of 100% at 3 years in patients with a pCR also compares favorably with similar cohorts of patients in whom pCR was also achieved 24 .…”

Neoadjuvant Chemoradiotherapy versus Chemotherapy for Gastroesophageal Junction Adenocarcinoma; Which Is the Optimal Treatment Option?

“…The long-term results of the POET trial [ 28 ] reported a trend to better overall survival after RCT, although our data, as long as previous long-term studies, do not confirm this finding [ 7 , 8 , 9 , 10 , 12 , 23 ]. Recently, patients with pCR after CT were reported to have better recurrence-free survival than those with pCR after RCT [ 29 ]. Moreover, it has to be kept in mind that radiation is no longer an option in the case of locoregional recurrence in patients already treated with RCT preoperatively.…”