Lymph Node Yield Is An Independent Predictor Of Survival In Rectal Cancer Regardless Of Receipt Of Neoadjuvant Therapy

Aims Lymph node yield (LNY) is used as a marker of adequate oncological resection. The American Joint Committee on Cancer (AJCC) currently recommends that at least 12 nodes are necessary to confirm node-negative disease for rectal cancer. A LNY of 12 is not always achieved, particularly in patients who have undergone neoadjuvant treatment. This study attempts to examine factors associated with LNY and its prognostic impact following neoadjuvant chemoradiation in rectal cancer. Methods The 2006-2011 National Cancer Data Base was queried for patients with clinical stage I-III rectal cancer who underwent a proctectomy. Suboptimal LNY was defined as \u3c12 lymph nodes examined. A mixed-effects multinomial logistic regression model was used to identify independent factors associated with LNY. Mixed-effects Cox proportional hazards models were used to estimate the adjusted effect of LNY on 5-year overall survival. Results 25...447 patients met inclusion criteria. Overall, 62% of the cohort received neoadjuvant chemoradiation and 32% had suboptimal LNY. The median LNY for patients who received neoadjuvant therapy was 13 (IQR: 9-18) and for patients who did not receive neoadjuvant therapy was 15 (IQR: 12-21). After risk adjustment, there was a 3.5-fold difference in the rate of suboptimal LNY among individual hospitals (27%-95%). Suboptimal LNY was independently associated with an 18% increased hazard of death among patients who did not receive neoadjuvant treatment and a 20% increased hazard of death among those who did receive neoadjuvant treatment when controlled for adjuvant treatment, staging, proximal/distal margins and other patient factors. Conclusions Suboptimal LNY is independently associated with worse overall survival regardless of neoadjuvant therapy, pathological staging and patient factors in rectal cancer. This finding underlies the importance and challenge of an optimal lymph node evaluation for prognostication, especially for patients receiving neoadjuvant therapy