Extensive lymphadenectomy may not increase patient survival with esophageal cancer

1. In a retrospective review of over 600 patients that underwent esophageal cancer surgery, there was no significant association between the total number of resected lymph nodes and disease-specific survival in esophageal cancer independent of other prognostic factors.

2. A greater number of metastatic lymph nodes were associated with increased mortality.

Evidence Rating Level: 2 (Good)           

Study Rundown: Current clinical guidelines for esophageal cancer recommend extensive removal of regional lymph nodes. However, due to lack of quality evidence, it is unclear whether extensive lymphadenectomy is beneficial for patient survival. The purpose of this study was to elucidate the association between the number of removed lymph nodes and mortality among patients who underwent surgery for esophageal cancer.

The study analyzed the outcomes of over 600 patients that underwent esophagectomy with variable lymphadenectomies. At the conclusion of the study, there was no difference in overall or disease-specific 5-year survival among all lymphadenectomy levels (0-10, 11-14, 15-20 and 21-52 nodes). The lack of positive association persisted when controlled for confounding factors, such as age, pathological T category, tumor differentiation, margin status, response to preoperative chemotherapy and calendar period. Higher number of metastatic lymph nodes and higher ratio of metastatic nodes to all nodes were significantly associated with increased overall and disease-specific 5-year survival, as shown in previous studies. This study challenges the current guidelines and may necessitate further research to validate the findings. Major merits of this study were the large cohort of patients, the control for confounding factors, and no loss of follow-up of patients, strengthening the validity of the results. However, the study is limited by its single-institution data.

Click to read the study in JAMA Surg

Relevant Reading: Extent of lymph node removal during esophageal cancer surgery and survival

In-Depth [retrospective cohort]: The study retrospectively reviewed a total of 606 patients, who were surgically treated for esophageal cancer at St. Thomas’ Hospital in London, UK, between 2000 and 2012, with follow-up until January 2014. There was no loss of follow-up. The number of resected lymph nodes, the number of malignant nodes and the ratio of malignant nodes to all nodes were employed as exposure. All cause and disease-specific 5-year survival were the outcome measures. Cox proportional hazard modeling and logistic regression were used for statistical analysis. There was no statistically significant difference in all-cause and disease-specific 5-year survival among all quartiles of lymphadenectomy (0-10, 11-14, 15-20 and 21-52 nodes). The crude hazard ratio (HR) for disease-specific 5-year survival was 0.97 (95%CI: 0.68-1.39) in the highest quartile of lymphadenectomy (21-52 nodes), compared to the lowest quartile of lymphadenectomy (0-10 nodes). The trend remained the same when adjusted for other prognostic factors, such as age, pathological T category, tumor differentiation, margin status, response to preoperative chemotherapy, and calendar period. The presence of metastatic lymph nodes and a high metastatic-to-all nodes ratio were strong predictor factors for all-cause and disease-specific 5-year survival. The crude HR for disease-specific 5-year survival was 8.04 (95%CI: 5.42-11.90) in the group of patients with more than 6 metastatic lymph nodes compared to those without any metastatic nodes. A similar trend was observed for the ratio of metastatic-to-all nodes. The HR for the number of metastatic lymph nodes and the ratio of metastatic-to-all nodes remained significant on the multivariate analysis adjusted for the aforementioned prognostic factors.

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