Controversy currently exists about the optimum preoperative treatment platform for locoregionally advanced esophageal cancer, namely, preoperative chemoradiotherapy (preoperative C/RT) or preoperative chemotherapy alone. We therefore reviewed sequential phase II/III trials performed at a single institution to assess the impact of preoperative chemotherapy versus preoperative C/RT strategies.

In all, 157 esophageal cancer patients were sequentially enrolled in phase II/III trials at the University of Texas M.D. Anderson Cancer Center from March 27, 1990, to March 8, 2005. The treatment approaches included preoperative chemotherapy, n = 76 (INT 113 and ID90-01); preoperative C/RT, n = 81 (ID96-189 and DM98-349). Analysis was by intention to treat. Factors evaluated included demographics, preoperative staging, type of surgery, pathology, adjuvant therapies, and long-term outcome.

Adenocarcinoma predominated (85%), with cT3 (73%) and cN1 (43%). No significant difference was noted between groups in demographics or perioperative mortality. More patients with preoperative C/RT were staged with endoscopic ultrasound (52% versus 9%, p < 0.001). Preoperative C/RT demonstrated increased pathologic complete response (28% versus 4%, p < 0.001) and overall survival (3 years, 48% versus 29%, p = 0.04). Preoperative C/RT was a significant independent predictor of improved overall survival (hazard ratio 0.58, 95% confidence interval: 0.37 to 0.90, p = 0.015) and disease-free survival (hazard ratio 0.55, 95% confidence interval: 0.35 to 0.85, p = 0.007) in multivariable regression.

In sequential phase II/III trials involving locoregionally advanced esophageal cancer patients, preoperative C/RT was associated with improved overall and disease-free survival rates (p = 0.046 and p = 0.015, respectively) and increased pathologic complete response (p < 0.001) compared with preoperative chemotherapy.