Prognostic impact of postoperative complications after neoadjuvant therapy followed by esophagectomy for esophageal cancer: An exploratory analysis of phase III trial JCOG1109.

356 Background: We previously reported that postoperative complications after esophagectomy were significantly associated with poor long-term prognosis in the prospective randomized trial JCOG9907 (Ann Surg, 2017). JCOG1109 evaluated the efficacy and safety of neoadjuvant docetaxel plus cisplatin plus 5-FU (DCF), radiation with cisplatin plus 5-fluorouracil (CF-RT) compared with cisplatin plus 5-fluorouracil (CF) for locally advanced esophageal squamous cell carcinoma, and demonstrated the superiority of DCF compared with CF in improving overall survival (OS). In this exploratory analysis, we investigated the association between postoperative complications and prognosis in JCOG1109, where more intensive preoperative therapies and thoracoscopic esophagectomy (TE) were introduced. Methods: Patients with potentially resectable advanced thoracic esophageal cancer were randomly assigned to CF, DCF, or CF-RT therapies and followed by open esophagectomy (OE) or TE with regional lymphadenectomy in JCOG1109. The impacts of postoperative complications (≥ Grade 2) on long-term prognosis including OS and progression-free survival (PFS) were investigated in each of the three preoperative therapies. Results: Between December 2012 and July 2018, 601 patients were randomized (CF/DCF/CF-RT; 199/202/200). Of 589 eligible patients, 541 patients underwent esophagectomy (183/181/177). Any postoperative complications, pneumonia, anastomotic leakage, recurrent laryngeal nerve paralysis, or infectious complications had no significant impact on OS in each of the three arms. When divided into OE or TE, the impact of any postoperative complications on OS was attenuated by introducing TE in each of three arms; from neoadjuvant CF followed by OE group [hazard ratio (HR) 1.557, 95% confidence interval (CI) 0.881-2.752] to TE group [HR 0.802, 95% CI 0.424-1.515], from neoadjuvant DCF followed by OE group [HR 1.151, 95% CI 0.575-2.306] to TE group [HR 0.703, 95% CI 0.3363-1.471], and from neoadjuvant CF-RT followed by OE group [HR 1.548, 95% CI 0.840-2.852] to TE group [HR 1.186, 95% CI 0.627-2.245]. Conclusions: JCOG1109 showed no association between postoperative complications and long-term prognosis. The prognostic impact of postoperative complications might be attenuated by the introduction of minimally invasive esophagectomy (open to thoracoscopy) even after more intensified preoperative therapy (CF to DCF or CF to CF-RT). Clinical trial information: CRB3180009.