K. A. Mirkin1,2, C. S. Hollenbeak1,2, J. Wong2 1Penn State University College Of Medicine,Department Of Public Health Sciences,Hershey, PA, USA 2Penn State University College Of Medicine,Department Of Surgery,Hershey, PA, USA
Introduction:
Surgical resection is the mainstay of pancreatic cancer treatment, however, the ideal lymphadenectomy remains unsettled. Several meta-analyses have concluded that extended lymphadenectomies do not impact survival. The objective of this study was to determine if number of examined lymph nodes (eLN), a proxy for lymphadenectomy, and lymph node ratio (LNR) impact survival.
Methods:
The U.S. National Cancer Data Base (2003-2011) was reviewed for patients with clinical stage I and II resected pancreatic adenocarcinoma. Patients who received neoadjuvant therapy were excluded. Patients were stratified by eLN: 0-6, 7-12, 13-15, and >15, and LNR (LNR= #positive nodes/ #eLN):0, 0-0.2, 0.2-0.4, 0.4-0.8, and >0.8. Univariate and multivariate survival analyses were performed.
Results:
14,807 patients with clinical stages I-II resected pancreatic adenocarcinoma were included. Of these, 15.6% (N=2,309) of patients had 0-6 eLN, 27.1% (N=4,012) had 7-12, 13.4% (N=1,977) had 13-15, and 38.6% (N=5,709) had >15 eLN. The majority of patients underwent pancreaticoduodenectomy (N=7,720, 55.1%), while the remainder underwent distal pancreatectomy (N=1,833, 13.1%), total pancreatectomy (N=1,850, 13.2%) and other (N=2,604, 18.6%). Patients who underwent pancreaticoduodenectomy had a median eLN of 11, while those who underwent distal or total pancreatectomy or another procedure had 14. Patients with >15 eLN had significantly improved survival over the other cohorts in both node negative and node positive disease (P<0.001, both). After controlling for patient, disease, and treatment characteristics, patients with 7-12, 13-15, and >15 eLN had improved survival relative to patients with 0-6 eLN (HR 0.87, p<0.001, HR 0.89, p=0.002, HR 0.82, p<0.001, respectively).
32.6% (N=4,829) of patients had a LNR of 0, 29.8% (N=4,414) £0.2, 9.2% (N=2,843) 0.2-0.4, 11.0% (N=1,643) 0.4-0.8, and 1.9% (N=278) had a LNR >0.8. Patients with LNR 0 had improved survival in T1-T3 disease (P<0.01). After controlling for patient, disease and treatment characteristics, higher LNR was negatively associated with survival (LNR 0-0.2: HR 1.44, p<0.001, LNR 0.2-0.4: HR 1.82, p<0.001, LNR 0.4-0.8: 2.03, p<0.001, LNR >0.8, p<0.001).
Even when a suboptimal number of lymph nodes were examined (eLN £6 or £12), higher LNR remained an independent predictor for mortality.
Conclusion:
Greater lymph node retrieval in stage I & II pancreatic adenocarcinoma appears to have therapeutic and prognostic value, even in node-negative disease, suggesting a comprehensive lymphadenectomy is beneficial. Lymph node ratio is inversely related to survival and may be useful when suboptimal lymph node retrieval is performed.