M. Raoof1, V. N. Nfonsam1, J. Warneke1, R. Krouse1,2 1University Of Arizona College Of Medicine,Surgical Oncology,Tucson, AZ, USA 2Southern Arizona Veterans Affairs Health Care System,Surgical Care Line,Tucson, AZ, USA
Introduction: Neoadjuvant therapy for locally advanced rectal cancer reduces the yield of lymph node (LN) sampling. In the setting of pathologically negative LNs after neoadjuvant therapy, the significance of the number of LNs retrieved is unclear. Studies in the literature have reported conflicting results. We hypothesized that the number of negative lymph nodes harvested is related to long-term survival.
Methods: This is a study of a contemporary cohort from NCI’s SEER database over a 7-year period (Jan, 2004- Nov, 2010). Patients with locally advanced rectal adenocarcinoma who underwent neoadjuvant therapy and had pathologically negative LNs in resected specimens were included. The collaborative staging fields in the SEER database record worst T-stage (i.e. clinical T-stage unless pathological T-stage was worse, in which case pathological T-stage is recorded). This allowed a unique opportunity to distinguish T-stage progression vs. T-stage stable disease or regression. Pathologic LN stage was available for all patients and by inclusion criteria were N0. Clinical LN status was available for 73% of patients. Survival analysis was performed using the Kaplan-Meier method. Inferential statistics were performed using a Cox-proportional hazard model.
Results: Of the total 3864 patients that met the strict inclusion criteria, 65% were males, 82% were white and 51% were ≥60 years of age. Majority had T3 (T1, 9%; T2, 19%; T3, 67%, T4 5%), clinical LN positive (Positive, 44%; Negative, 29%; Unknown, 27%) and moderately differentiated (G1, 6%; G2, 71%; G3, 10%; G4, 0.5%) tumors. Median lymph nodes retrieved were 12 (IQR 7-16). Median follow-up was 28 months (IQR 12-47). Using the minimum p-value approach we identified a cut-off of 7 LNs provides oprtimal stratification of patients in terms of overall survival (Figure). A multivariate Cox-proportional hazard model adjusted for age, race, T-stage, grade, clinical LN status and T-stage response to neoadjuvant therapy demonstrated that patients who have >7 LNs examined have a better overall (hazard ratio 0.66; 95% CI 0.53-0.81; p < .0001) and cancer-specific survival (hazard ratio 0.64; 95% CI 0.50-0.83; p = 0.001) compared with patients who had ≤7 LNs examined.
Conclusion: This is the largest study to date that demonstrates the prognostic significance of LN sampling in patients with rectal cancer after neoadjuvant therapy. Patients with less than seven LNs harvested have worse survival and should be considered for more aggressive adjuvant therapy and follow-up strategy.
