Perioperative chemotherapy versus neoadjuvant chemoradiotherapy for esophageal or GEJ adenocarcinoma: A propensity score-matched analysis comparing toxicity, pathologic outcome, and survival

Objectives: To evaluate toxicity, pathologic outcome, and survival after perioperative chemotherapy (pCT) compared to neoadjuvant chemoradiotherapy (nCRT) followed by surgery for patients with resectable esophageal or gastroesophageal junction (GEJ) adenocarcinoma. Methods: Consecutive patients with resectable esophageal or GEJ adenocarcinoma who underwent pCT (epirubicin, cisplatin, and capecitabine) or nCRT (paclitaxel, carboplatin, and 41.4 Gy) followed by surgery in a tertiary referral center in the Netherlands were compared. Propensity score matching was applied to create comparable groups. Results: Of 193 eligible patients, 21 were discarded after propensity score matching; 86 and 86 patients who underwent pCT and nCRT, respectively, remained. Grade ≥3 thromboembolic events occurred only in the pCT group (19% vs. 0%, P < 0.001), whereas grade ≥3 leukopenia occurred more frequently in the nCRT group (14% vs. 4%, P = 0.015). No significant differences regarding postoperative morbidity and mortality were found. Pathologic complete response was more frequently observed with nCRT (18% vs. 11%, P < 0.001), without significantly improving radicality rates (95% vs. 89%, P = 0.149). Both strategies resulted in comparable 3-year progression-free survival (pCT vs. nCRT: 46% vs. 55%, P = 0.344) and overall survival rates (49% vs. 50%, P = 0.934). At 3-year follow-up, fewer locoregional disease progression occurred in the nCRT group (19% vs. 37%, P = 0.024). Conclusions: Compared to perioperative chemotherapy, neoadjuvant chemoradiotherapy achieves higher pathologic response rates and a lower risk of locoregional disease progression, without improving survival.