Patterns and predictors of failure following tri-modality therapy for locally advanced esophageal cancer

Background. Although tri-modality therapy is an acceptable standard of care in patients with locally advanced esophageal cancer, data regarding patterns of failure is lacking. We report bi-institutional patterns of failure experience treating patients using tri-modality therapy. Materials and methods. We retrospectively reviewed patients who underwent chemoradiation followed by esophagectomy between 2006 and 2011 at two NCI-designated cancer centers. First failure sites were categorized as local, regional nodal, or distant. Statistical analysis was performed using Fisher's exact test, nonparametric Wilcoxon rank-sum test, and multiple logistic regression. Kaplan-Meier curves were generated for relapse-free survival (RFS) and overall survival. Results. A total of 132 patients met the inclusion criteria with a median age of 62 (range 36-80) and median follow-up of 28 months (range 4-128). There were a total of six (4.5%) local, 13 (10%) regional nodal, and 32 (23.5%) distant failures. Local failure was correlated with fewer lymph nodes (LN) assessed (p=0.01) and close/ positive margins (p<0.01). Regional nodal failure was correlated with fewer LN assessed (p<0.01) and larger pretreatment tumor size (p=0.04). Patients with≤13 LN evaluated had an inferior locoregional RFS versus patients with413 LN evaluated (p=0.003). Distant recurrence was correlated with higher pathologic nodal stage (p<0.001), ulceration (p=0.017), perineural invasion (p=0.029), residual disease (p=0.004), and higher post-treatment PET SUV max (p=0.049). Patients with a pathologic complete response (OR 0.19, 95% CI 0.05-0.68) were less likely to experience distant recurrence. Conclusion. Tumor and treatment factors may predict for failure in patients undergoing tri-modality therapy for locally advanced esophageal cancer. Further data is needed to identify patterns of failure in these patients.