Extended Right Thoracic Approach Compared With Limited Left Thoracic Approach for Patients With Middle and Lower Esophageal Squamous Cell Carcinoma: Three-year Survival of a Prospective, Randomized, Open-label Trial.

OBJECTIVE: To investigate whether survival is improved by using the right thoracic approach (extended lymphadenectomy) compared with the left thoracic approach (limited lymphadenectomy) for esophageal cancer. BACKGROUND: The optimal surgical technique for esophageal cancer remains unclear. METHODS: Between May 2010 and July 2012, 300 patients with middle and lower thoracic esophageal carcinoma were randomized to receive esophagectomy through either the right or left thoracic approach. Of these, 286 patients with squamous cell carcinoma determined by postoperative pathology were included in this analysis. Disease-free survival (DFS) and overall survival (OS) were compared between the right (n = 146) and left thoracic groups (n = 140). RESULTS: The median follow-up was 55.9 months [95% confidence interval (CI): 53.1-58.6]. The 3-year DFS rates were 62% and 52% in the right and left thoracic arms, respectively [hazard ratio (HR) 0.709; 95% CI, 0.506-0.995; P = 0.047, log-rank test]. The 3-year OS rates were 74% and 60%, respectively (HR, 0.663; 95% CI, 0.457-0.961; P = 0.029). Subgroup analyses revealed longer DFS in the right thoracic arm (vs left thoracic arm) in patients with lymph node involvement (HR, 0.632; 95% CI, 0.412-0.969, P = 0.034), but not in patients without lymph node involvement (HR, 0.757; 95% CI, 0.434-1.320, P = 0.325), and in patients with R1-2 resection margins (HR, 0.495; 95% CI, 0.290-0.848, P = 0.009), but not R0 margins (HR, 0.944; 95% CI, 0.603-1.477, P = 0.801). CONCLUSIONS: Compared with the left thoracic approach, the right thoracic approach associated with increased DFS and OS in esophageal squamous cell carcinoma patients, particularly in those with lymph node involvement and/or R1-2 resection margins.

Esophagectomy With Three-Field Versus Two-Field Lymphadenectomy for Middle and Lower Thoracic Esophageal Cancer: Long-Term Outcomes of a Randomized Clinical Trial.

INTRODUCTION: The optimal extent of lymphadenectomy during esophagectomy remains unclear. In this trial, we aim to clarify whether three-field (cervical-thoracic-abdominal) lymphadenectomy improved patient survival over two-field (thoracic-abdominal) lymphadenectomy for esophageal cancer. METHODS: Between March 2013 and November 2016, a total of 400 patients with middle and lower thoracic esophageal cancer were included and randomly assigned to undergo esophagectomy with either three- or two-field lymphadenectomy at a 1:1 ratio. Analyses were done according to the intention-to-treat principle. The primary end point was overall survival (OS), calculated from the date of randomization to the date of death from any cause. RESULTS: Demographic characteristics were similar in the two arms. The median follow-up time was 55 months (95% confidence interval [CI]: 52-58). OS (hazard ratio [HR] = 1.019, 95% CI: 0.727-1.428, p = 0.912) and the disease-free survival (DFS) (HR = 0.868, 95% CI: 0.636-1.184, p = 0.371) were comparable between the two arms. The cumulative 5-year OS was 63% in the three-field arm, as compared with 63% in the two-field arm; 5-year DFS was 59% and 53%, respectively. On the basis of whether the patients had mediastinal or abdominal lymph node metastasis or not, OS was also comparable between the two arms. In this cohort, only advanced tumor stage (pathologic TNM stages III-IV) was identified as the risk factor associated with reduced OS (HR = 3.330, 95% CI: 2.140-5.183, p < 0.001). CONCLUSIONS: For patients with middle and lower thoracic esophageal cancer, there was no improvement in OS or DFS after esophagectomy with three-field lymphadenectomy over two-field lymphadenectomy.

Oncogenic mutations are associated with histological subtypes but do not have an independent prognostic value in lung adenocarcinoma.

Lung adenocarcinomas have diverse genetic and morphological backgrounds and are usually classified according to their distinct oncogenic mutations (or so-called driver mutations) and histological subtypes (the de novo classification proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society [IASLC/ATS/ERS]). Although both these classifications are essential for personalized treatment, their integrated clinical effect remains unclear. Therefore, we analyzed 981 lung adenocarcinomas to detect the potential correlation and combined effect of oncogenic mutations and histological subtype on prognosis. Analysis for oncogenic mutations included the direct sequencing of EGFR, KRAS, HER2, BRAF, PIK3CA, ALK, and RET for oncogenic mutations/rearrangements, and a rereview of the IASLC/ATS/ERS classification was undertaken. Eligible tumors included 13 atypical adenomatous hyperplasia/adenocarcinoma in situ, 20 minimally invasive adenocarcinomas, 901 invasive adenocarcinomas, 44 invasive mucinous adenocarcinomas, and three other variants. The invasive mucinous adenocarcinomas had a lower prevalence of EGFR mutations but a higher prevalence of KRAS, ALK, and HER2 mutations than invasive adenocarcinomas. Smoking, a solid predominant pattern, and a mucinous component were independently associated with fewer EGFR mutations. The ALK rearrangements were more frequently observed in tumors with a minor mucinous component, while the KRAS mutations were more prevalent in smokers. In addition, 503 patients with stage I-IIIA tumors were analyzed for overall survival (OS) and relapse-free survival. The stage and histological pattern were independent predictors of relapse-free survival, and the pathological stage was the only independent predictor for the OS. Although patients with the EGFR mutations had better OS than those without the mutations, no oncogenic mutation was an independent predictor of survival. Oncogenic mutations were associated with the novel IASLC/ATS/ERS classification, which facilitates a morphology-based mutational analysis strategy. The combination of these two classifications might not increase the prognostic ability, but it provides essential information for personalized treatment.