What is the clinical value of a margin negative resection in lymph node positive gallbladder cancer?

Abstract

Objective: Achieving free surgical margins in gallbladder cancer (GBAC) often requires an operation more morbid than cholecystectomy. There is little data examining the value of a margin negative resection in patients with lymph node positive GBAC and thus high risk for distant disease recurrence. Methods: We queried the National Cancer Database to identify patients undergoing resection for lymph node positive GBAC between 2004 and 2012. Patients receiving neoadjuvant chemoradiotherapy and those with gross residual (R2) disease were excluded. Multivariable and Cox Models adjusted for age, facility type, Charlson index, margin status, tumor grade, pathologic stage, number of nodes examined, procedure type and adjuvant chemoradiotherapy. Results: 826 (78.1%) patients had free microscopic margins on final pathology (R0); 231 (21.9%) had microscopic positive margins (R1). Multivariable regression identified limited (≤2 nodes) lymphadenectomy (OR 2.014, 95% CI [1.366, 2.971]), pathologic N2 (OR 3.100, 95% CI [1.339, 7.178]) and T3 disease (OR 4.670, 95% CI [1.479,14.751]) as independently associated with R1 resection. Cox modeling identified R0 resection (HR 0.639, 95% CI [0.531, 0.769]) and receipt of adjuvant chemoradiotherapy (HR 0.498, 95% CI [0.416, 0.597]) as independently associated with improved overall survival and advanced age (HR 1.432, 95% CI [1.119, 1.834]), T3 disease (HR 1.895, 95% CI [1.176, 3.053]), and Charlson score>2 (HR 1.450, 95% CI [1.092, 1.925]) with poor survival. Patients undergoing R0 resection had median survival of 20.6 months compared to 9.99 months for those undergoing R1 resection (p < 0.0001). Conclusion: For patients with node positive GBAC, operations that carry greater risk of morbidity but achieve negative surgical margins are justifiable.