Is the N1c category of the new American Joint Committee on cancer staging system applicable to patients with rectal cancer who receive preoperative chemoradiotherapy?

Background: Pericolorectal tumor deposits (TDs) are associated with adverse outcomes in patients with colorectal cancer, and the seventh edition of the American Joint Committee on Cancer (AJCC) staging system recently classified TDs without regional lymph node metastasis as category N1c. However, the definition of TDs has varied. Moreover, with the recent, widespread application of preoperative chemoradiotherapy (CRT) in rectal cancers, residual primary tumor confined to the mesorectum is not infrequent, and it is unclear whether the N1c category is appropriate for these tumors.

Methods: To evaluate the prognostic significance of the N1c classification in patients with rectal cancers after preoperative CRT, the authors reviewed the histologic features of 136 rectal cancers that were classified previously with a tumor classification of 3 [T3], negative lymph nodes [N0], and no metastasis [M0] based on the pathologic extent of disease (ypT3N0M0). These tumors were reclassified according to the new AJCC staging system, and patient outcomes were analyzed.

Results: Perirectal TDs were detected in 16 of 136 patients (11.8%). Patterns of TD included a separate nodule pattern in 6 patients (38%), a perivascular pattern in 4 patients (25%), a perineural pattern in 4 patients (25%), and a lymphatic pattern in 2 patients (12%). By using the new N1c category, 120 patients (88.2%) were classified with yp-stage IIA disease, 6 patients (4.4%) were classified with yp-stage IIIA disease, and 10 patients (7.4%) were classified with yp-stage IIIB disease. Kaplan-Meier survival analysis indicated that there were no significant differences between the TD-positive and TD-negative groups in disease-free survival (DFS) or overall survival (OS) (P = .48 for both; log-rank test). In addition, the reclassified TMN stage was not related to DFS (P = .17) or OS (P = .072).

Conclusions: The category N1c may not be appropriate for patients with rectal cancer after preoperative CRT, because the definition of ypN1c was confusing and did not have prognostic significance.