A retrospective comparison of neoadjuvant chemoradiotherapy regimens for locally advanced esophageal cancer

Preoperative chemoradiotherapy (CRT) with carboplatin/paclitaxel has been shown to increase survival in patients with esophageal cancer, including gastroesophageal junction (GE) junction cancer, over surgery alone; however, there have been no studies comparing the different neoadjuvant CRT regimens. We retrospectively evaluated the long-term results of trimodality therapy for patients with locally advanced esophageal cancer treated on several chemotherapy regimens. Between 1999 and 2014, 215 patients with locally advanced esophageal cancer underwent neoadjuvant CRT followed by surgical resection. The median age was 62 years (range 21-84), 80.5% were men and 86% had adenocarcinoma. The following chemotherapy regimens were administered: cisplatin/5FU (14.9%), cisplatin/irinotecan (35.8%), carboplatin/paclitaxel (35.8%), and other (9.7%). The majority of patients (92.1%) received a radiation dose of 50.4 Gy. Predictors of toxicities and surgical complications were assessed using logistic regression. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and proportional hazards regression was used to model time-to-event outcomes. The median follow-up among surviving patients was 4.1 years (range 0.4,13). The median OS was 3.0 years from time of diagnosis and OS was 36.8% at 5 years. RFS was 34.9% at 5 years. After neoadjuvant CRT, 34.7% of patients achieved a pathologic complete response including 60.7% of squamous cell carcinoma patients and 18.4% of adenocarcinoma patients (P < 0.001) and 66% were downstaged. Of the variables examined, pathologic stage, preoperative baseline cardiac comorbidity, postoperative cardiac or pulmonary complications, and chemotherapy regimen were associated with OS. Using cisplatin and 5FU as the reference regimen, patients treated with carboplatin/paclitaxel had significantly improved OS (HR = 0.47, P = 0.017 after adjusting for surgery type, radiation modality, baseline cardiac comorbidity, and preoperative stage) with 5-year OS rate of 66%. The most common surgical complications were cardiac in 61 patients (28.5%) and pulmonary in 52 patients (24.3%). Cardiac complications were associated with age (OR 1.05, P = 0.007) and cardiac comorbidity (OR 2.6, P = 0.02) and pulmonary complications with female gender (OR 3.98, P < 0.001). Forty-four patients (20.5%) required readmission within 30 days of discharge, and readmission was associated with cardiac comorbidity (OR 2.7, P = 0.017). Three patients died within 30 days of surgery. We observed an association between neoadjuvant carboplatin/paclitaxel and improved overall survival that requires confirmation in a prospective randomized trial.