Pathologic Response after Neoadjuvant Therapy is the Major Determinant of Survival in Patients with Esophageal Cancer

Esophageal cancer remains a malignancy with high morbidity and mortality despite improvements to diagnosis, staging, chemotherapy, radiation, and surgery. Neoadjuvant therapy (NT) may improve oncologic outcome in many patients, however the degree to which patients benefit remains unclear. We examined the relationship between pathologic response to NT and magnitude of benefit in patients with esophageal cancer. Using a comprehensive esophageal cancer database, we identified patients who underwent esophagectomy between 1994 and 2008. Pathologic response was denoted as complete (pCR), partial (pPR), and nonresponse (NR). Clinical and pathologic data were compared using Fisher's exact and chi-square when appropriate, while Kaplan-Meier estimates were used for survival analysis. We identified 347 patients who underwent esophagectomy, and 262 (75.5%) were treated with NT. The median age was 66 years (28-86 years) with median follow-up of 20 months (1-177 months). There were 106 (40.5%) patients exhibiting pCR, 95 (36.3%) with pPR, and 61 (23.3%) with NR. The rate of R0 resections was higher amongst pCR (100%) compared with 94.7% in pPR (P = 0.02) and 87.5% in NR (P = 0.0007). There were 15 (14.2%) recurrences in pCR, 22 (23.7%) in pPR, and 17 (28.8%) in NR (P = 0.04). Patients achieving pCR had 5-year disease-free survival (DFS) and overall survival (OS) of 52% and 52%, respectively, compared with 36% and 38% in pPR and 22% and 19% in NR (P < 0.0001, P < 0.0001). Esophageal cancer patients frequently succumb to their disease. However, patients treated with neoadjuvant therapy who achieve pCR have a higher rate of R0 resections, fewer recurrences, and improved 5-year OS and DFS.