Objective: The National Quality Forum has endorsed a 12 lymph node (LN) minimum as a surrogate measure of quality in colorectal cancer (CRC). The prognostic value of ultrastaging hematoxylin and eosin (H&E) negative LN’s (N0) using cytokeratin immunohistochemistry (CK-IHC) is unknown. We hypothesized that both surgical quality and focused pathology analysis improves survival.
Methods: Between 2001 and 2007, 253 evaluable patients with resectable CRC were enrolled. Multiple sectioning and CK-IHC was performed on N0 LN’s (stage II). The primary end-point was four-year disease free survival (DFS).
Results: There were 177 (70%) patients with N0 and 76 (30%) with N1 disease. Using ultrastaging in N0 patients, 36 (20%) were found to have micrometastases (MM). At a mean follow up of 3.4 years (± 1.6), 39 (15%) have recurred. The recurrence rate was only 3.7% in patients > 12 LN’s, negative by H&E and IHC, compared to 18.8% with <12 LN’s (P*=0.0032).
4 yr DFS based on AJCC Stage and LN number

Stage	N	<12LN’s	>12LN’s	P*
I	68	92%	98%	0.22
II	91	71%	95%	0.0083
III	94	70%	70%	0.72

* log rank test
Summary: This represents the first prospective report demonstrating that both surgical quality and nodal ultrastaging impacts survival in Stage II CRC. Patients with Stage II CRC with >12 LN’s negative for MM (N0i-) are likely cured by surgery alone. Both surgical and pathological quality measures are imperative in early CRC in order to improve patient selection for adjuvant chemotherapy.