A multicenter retrospective study of salvage surgery for patients with residual or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy: SURGES study.

422 Background: Salvage surgery is defined as an operation for patients with residual or recurrent tumors after definitive chemoradiotherapy (dCRT) with > 50 Gy. Although salvage surgery has been considered to improve prognosis, it is associated with a high incidence of postoperative morbidity and mortality. A previous meta-analysis by Faiz et al. reported anastomotic leakage, pulmonary disorder rates, and 90 day-mortality rates of 18.6%, 30.2%, and 8.8%, respectively. The aim of this study was to assess the efficacy and safety of salvage surgery in patients with residual or recurrent esophageal squamous cell carcinoma (ESCC) after dCRT and to explore the risk factors for postoperative complications and poor prognosis. Methods: This multi-institutional retrospective study enrolled patients treated with salvage surgery after dCRT between January 2017 and December 2021. The preoperative backgrounds of the patients were analyzed to assess their impact on survival or toxicity. Results: In total, 148 patients (59 with recurrent disease and 89 with residual disease) underwent salvage surgery at 10 leading hospitals in Japan. Post-dCRT ycT stages were T0/T1/T2/T3/T4: 12/25/30/78/3, and ycN stages were N0/N1/N2: 87/53/8. Among 136 patients who underwent esophagectomy, 108 underwent minimally invasive surgery and 28 underwent open surgery. Twelve patients had metastatic lymph nodes without primary disease. Severe postoperative complications (≧Clavien-Dindo Grade III) occurred in 39 (26.3%) patients and overall postoperative complications (≧Grade II) rate was 46.6%, including 19 (12.8%) anastomotic leakage and 25 (16.9%) pneumonia. Thirty- and 90-day mortality rates were observed in 0 and 5 (3.3%) patients, respectively. Multivariate logistic regression analysis showed that a total radiation dose ≥60 Gy (odds ratio [OR] 2.65, 95% confidence interval [CI] 1.07-6.55) and residual disease (OR 3.04, 95%CI 1.32-7.00) were associated with severe postoperative complications. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 48.9% and 40.0%, respectively (median follow-up time: 42.1 months). Multivariate analysis revealed that patients with a long interval between dCRT and salvage surgery (≥180 days) had significantly longer OS (hazard ratio [HR] 0.60, 95%CI 0.38-0.95, p=0.032), and ycN0 was associated with longer PFS (HR 0.56, 95%CI 0.36-0.87, p = 0.011). The total radiation dose was not an independent prognostic factor for either OS or PFS. Conclusions: Salvage surgery is safe and provides substantial long-term outcomes. In cases with a total radiation dose of ≥60 Gy and residual disease, special caution is required because of the higher incidence of postoperative morbidity. A longer interval between dCRT and salvage surgery and ycN0 were prognostic factors.