Patterns and risk of recurrence in patients with esophageal cancer with a pathologic complete response after chemoradiotherapy followed by surgery

Abstract

Objectives: A pathologic complete response in patients with locally advanced esophageal cancer after chemoradiotherapy and surgery is associated with improved overall and disease-free survival. Nevertheless, approximately one third of patients with a pathologic complete response still have a recurrence. The aim of this study was to evaluate risk factors and patterns of recurrence in patients with locally advanced esophageal cancer who achieved a pathologic complete response after chemoradiotherapy and surgery.

Methods: We performed a retrospective review of a single-institution database of 233 patients with stage II and III esophageal cancer with a pathologic complete response after chemoradiotherapy and surgery between 1997 and 2017. A multivariable competing risk-regression model was used to identify predictors of recurrence.

Results: A total of 61 patients exhibited recurrence in this cohort, 43 with adenocarcinoma and 18 with squamous cell carcinoma. Five-year cumulative incidence of recurrence did not vary by histology. Univariable analysis revealed that poor tumor differentiation (hazard ratio, 2.28; P = .022) and advanced clinical stage (hazard ratio, 1.89; P = .042) are predictors of recurrence in the esophageal adenocarcinoma subgroup, whereas poor tumor differentiation remained the only independent predictor on multivariable analysis in the entire cohort (hazard ratio, 2.28; P = .009). Patients with esophageal adenocarcinoma had a higher incidence of distant recurrences, and patients with esophageal squamous cell carcinoma demonstrated a higher incidence of loco-regional recurrence (P = .039).

Conclusions: Poor tumor differentiation is an independent risk factor for recurrence in patients with esophageal cancer with a pathologic complete response. Although there is no difference in the cumulative incidence of recurrence between esophageal adenocarcinoma and esophageal squamous cell carcinoma, patterns of recurrence appear to differ. Thus, treatment and surveillance strategies may be tailored appropriately.

Keywords: esophageal cancer; neoadjuvant chemoradiotherapy plus surgery; pathologic complete response; recurrence; survival.

Figure 1 –

Cumulative incidence of recurrence (CIR) stratified by histology. There was no significant difference in the cumulative incidence of disease recurrence between adenocarcinoma (adeno) and squamous cell carcinoma (SCC) histologies.

Figure 2 –

Cumulative incidence of distant recurrence (CIDR; A) and loco-regional recurrence (B) stratified by histology. A, Patients with adenocarcinoma (adeno) had a higher incidence of distant recurrences than patients with squamous cell carcinoma (SCC), though not statistically significant. B, Conversely, patients with SCC had a higher incidence of loco-regional recurrence than patients with adeno, and this was statistically significant.

Figure 3 –

Overall survival (OS) following recurrence stratified by interval to recurrence. OS was significantly lower in patients that recurred within 6 months post-treatment in comparison to those that recurred beyond this window.

Central Picture:

Cumulative incidence of recurrence after pathologic complete response, by histology.