Review article Systematic review and meta-analysis on the significance of salvage esophagectomy for persistent or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy K. Kumagai, 1 D. Mariosa, 2 J. A. Tsai, 1 M. Nilsson, 1 W. Ye, 2 L. Lundell, 1 I. Rouvelas 1 1 Center for Digestive Diseases, Karolinska University Hospital, Division of Surgery, CLINTEC, and 2 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden SUMMARY. The therapeutic strategy to be recommended in case of recurrent or persistent squamous cell esophageal cancer after completed definitive chemoradiotherapy (dCRT) has to be documented. Salvage esophagectomy has traditionally been recognized as a viable option, but many clinicians oppose the use of surgery due to the associated excessive morbidity and mortality. ‘Second-line’ chemoradiotherapy (CRT) without surgery may offer a treatment alternative in these difficult and demanding clinical situations. Until now, no comprehensive attempt has been carried out to compare the respective therapeutic options. A systematic literature search was performed focusing on studies comparing survival and treatment-related mortality in patients submitted to salvage esophagectomy or second-line CRT for recurrent or persistent esophageal squamous cell carcinoma after dCRT. Hazard ratios and risk ratios were calculated to compare the effect of these therapeutic strategies on overall survival and treatment-related mortality, respectively. Four studies containing 219 patients, with persistent or recurrent esophageal squamous cell carcinoma after dCRT, were included in the meta-analysis. The analysis revealed an overall survival benefit following salvage esophagectomy with a pooled hazard ratio for death of 0.42 (95% confidence interval 0.21–0.86, P = 0.017) compared with second-line CRT. A treatment-related mortality of 10.3% was recorded in the 36 patients who were submitted to salvage esophagectomy, while it was impossible to perform a meta-analysis comparing treatment-related mortality between the groups. Salvage esophagectomy offers significant gain in long-term survival compared with second-line CRT, although the surgery is potentially at a price of a high treatment-related mortality. KEY WORDS: chemoradiotherapy, esophageal cancer, esophagectomy, meta-analysis. INTRODUCTION Esophageal cancer is the eighth most common cancer worldwide and is still dominated by squamous cell tissue origin. These tumors cause approximately 400 000 deaths per year. 1 Although surgical resection preceded by neoadjuvant treatments represents standard of care for treatment with curative intent of locally advanced esophageal cancer, definitive chemoradiotherapy (dCRT) is also a potentially curative, nonsurgical option for these patients, with reported 5-year sur- vival rates in the range of 25–30%. 2,3 These data have been extrapolated to adenocarcinoma based on simi- larities in complete pathological response and overall survival. 4–6 However, problems do exist with dCRT in the form of persistent or recurrent disease in the esophagus, with reported figures as high as 60%. 3,7–9 The varia- tions are substantial depending on the design and length of follow-up, but above all on the paucity of techniques to diagnose and monitor both recurrent local disease and the degree of morphological response. Given the high risk for incomplete response or recurrent neoplastic growth, the question arises which therapies can be offered in these clinical situa- tions. Therapeutic alternatives hereby are represented Address correspondence to: Dr Koshi Kumagai, MD, PhD, Center for Digestive Diseases, K53, Karolinska University Hospital, Division of Surgery, CLINTEC, Stockholm 141 86, Sweden. Email: koshi.kumagai@gmail.com Disclosure: The authors declare no conflict of interest. Synopsis: This meta-analysis, comparing salvage esophagectomy versus chemotherapy or radiotherapy without surgery for persistent or recurrent esophageal cancer after definitive chemoradiotherapy, demonstrates that salvage surgery offers significant advantages in terms of long-term survival. Diseases of the Esophagus (2015) ••, ••–•• DOI: 10.1111/dote.12399 © 2015 International Society for Diseases of the Esophagus 1