Extent of lymph node removal during esophageal cancer surgery and survival.
BACKGROUND
It is unclear how the extent of surgical lymph node clearance influences prognosis after surgery for esophageal cancer.


METHODS
This nationwide, population-based cohort study included 1044 esophageal cancer patients who had undergone esophagectomy between 1987 and 2010 in Sweden, with follow-up until 2012. The independent role of lymph node removal in relation to survival was analyzed using Cox proportional hazards regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for age, sex, comorbidity, tumor (T) stage, neo-adjuvant treatment, surgeon volume, and calendar period. Statistical tests were two-sided, except tests for trend.


RESULTS
Analyzed as a linear variable, a higher number of lymph nodes removed did not influence the overall five-year mortality (adjusted HR = 1.00, 95% CI = 0.99 to 1.01). Patients in the third (7-15 nodes) and fourth (16-114 nodes) quartiles of removed nodes did not demonstrate any decreased overall five-year mortality compared with those in the lowest two quartiles (<7 nodes) (HR = 1.13, 95% CI = 0.95 to 1.35 and HR = 1.17, 95% CI = 0.94 to 1.46, respectively). In early T stages (Tis-T1) the hazard ratios indicated a worse survival with more lymphadenectomy using the median as cutoff (HR = 1.53, 95% CI = 1.13 to 2.06). Increased lymph node removal did not decrease mortality in any specific T stage. A greater number of metastatic nodes and a higher positive-to-negative node ratio were associated with strongly increased mortality. All results were similar when disease-specific mortality was analyzed.


CONCLUSIONS
This population-based study indicates that more extensive lymph node clearance during surgery for esophageal cancer may not improve survival. These results challenge current clinical guidelines, and further research is needed to change clinical practice.
Department of Molecular medicine and Surgery, Karolinska Institutet, Stockholm, Sweden (MvdS, AJ, PL, JL); Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (BW); Division of Cancer Studies, King's College London, London, UK (JL).
Maartje
M
van der Schaaf
Department of Molecular medicine and Surgery, Karolinska Institutet, Stockholm, Sweden (MvdS, AJ, PL, JL); Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (BW); Division of Cancer Studies, King's College London, London, UK (JL).
Asif
A
Johar
Department of Molecular medicine and Surgery, Karolinska Institutet, Stockholm, Sweden (MvdS, AJ, PL, JL); Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (BW); Division of Cancer Studies, King's College London, London, UK (JL).
Bas
B
Wijnhoven
Department of Molecular medicine and Surgery, Karolinska Institutet, Stockholm, Sweden (MvdS, AJ, PL, JL); Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (BW); Division of Cancer Studies, King's College London, London, UK (JL).
Pernilla
P
Lagergren
Department of Molecular medicine and Surgery, Karolinska Institutet, Stockholm, Sweden (MvdS, AJ, PL, JL); Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands (BW); Division of Cancer Studies, King's College London, London, UK (JL). jesper.lagergren@ki.se.
Jesper
J
Lagergren
D000230:Adenocarcinoma / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000601:surgery; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D016629:Esophagectomy / Q000379:methods* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008197:Lymph Node Excision / Q000379:methods* / Q000401:mortality; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D016016:Proportional Hazards Models; D016019:Survival Analysis; D015996:Survival Rate; D013548:Sweden / Q000453:epidemiology