BackgroundThe management of patients with a complete clinical response after neoadjuvant therapy for rectal adenocarcinoma is controversial. Those who advocate for resection point out the inaccuracy of N-staging with current imaging modalities. The objective of this study is to determine the impact of residual nodal involvement after complete tumor regression after neoadjuvant (chemo)radiotherapy. MethodsThe 2004 to 2014 National Cancer Database was queried for patients undergoing proctectomy for nonmetastatic rectal adenocarcinoma who had received neoadjuvant (chemo)radiotherapy and with ypT0 on final pathology. Patients were grouped based on pathologic nodal stage: ypT0N- and ypT0N+. The main outcome was 5-year overall survival. ResultsThere were 5,156 patients with ypT0N- and 527 with ypT0N+. Mean lymph node harvest was similar (ypT0N- 12.2 nodes [standard deviation 9.1] vs ypT0N+ 11.6 nodes [standard deviation 10.3]; P = .086). Patients with ypT0N+ were more likely to have had clinically involved nodes (P < .001) and earlier clinical T-stage (P = .002). Overall survival at 5 years was less for patients with ypT0N+ (80% vs 86%, log-rank P = .014). ypT0N+ was independently associated with worse overall survival (hazard ratio 1.74, 95% confidence interval 1.33–2.28). ConclusionResidual nodal involvement despite complete tumor regression was associated with worse 5-year overall survival compared to complete pathologic response. Additional therapy should be considered in the presence of complete clinical tumor regression after neoadjuvant (chemo)radiotherapy.