Prognostic Impact of Postoperative Complications After Neoadjuvant Therapy Followed by Esophagectomy for Esophageal Cancer

OBJECTIVE: Complications after esophagectomy are associated with poor long-term outcomes; however, the prognostic impacts of postoperative complications in patients receiving intensive neoadjuvant chemotherapy remain unclear. This study aimed to investigate the association between postoperative complications and the prognosis of patients receiving intensive neoadjuvant treatment. SUMMARY BACKGROUND DATA: This study is a supplementary analysis of JCOG1109, which is a phase III randomized trial that assessed the efficacy of neoadjuvant doublet chemotherapy (cisplatin plus 5-fluorouracil [CF]), triplet chemotherapy (docetaxel plus cisplatin plus 5-FU [DCF]), and chemoradiotherapy (radiation with CF [CF-RT]) in patients with locally advanced esophageal cancer. METHODS: Patients were randomly assigned to one of the three preoperative therapies, followed by open esophagectomy (OE) or thoracoscopic esophagectomy (TE) with regional lymphadenectomy. Postoperative complications (Grade ≥2) and their impacts on overall survival (OS) and progression-free survival (PFS) were assessed within each arm. RESULTS: A total of 601 patients were randomized (CF/DCF/CF-RT: 199/202/200) and 541 underwent esophagectomy (CF/DCF/CF-RT: 183/181/177) between 2012 and 2018. Postoperative complications, including pneumonia, anastomotic leakage, recurrent laryngeal nerve paralysis, and infectious complications, exhibited no significant impact on OS in any treatment arm. TE introduction appeared to attenuate the prognostic impact of complications: hazard ratios for OS shifted from 1.557 to 0.802, from 1.151 to 0.703, and from 1.548 to 1.186 in the CF, DCF, and CF-RT arms, when comparing OE with TE, respectively. CONCLUSION: In this exploratory analysis of JCOG1109, postoperative complications were not significantly associated with prognosis. Minimally invasive esophagectomy, such as TE and intensified neoadjuvant therapy, may reduce the negative prognostic impact of complications.