Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer

Background: The standard treatment for locally advanced rectal cancer is preoperative cheimoradiation and total mesorectal excision. After surgery, tumors are classified according to the depth of tumor invasion, nodal involvement, and tumor regression grade. However, these staging systems do not provide information about the distribution of residual cancer cells within the bowel wall. Objective: This study aimed to determine the distribution of residual cancer cells in each layer of the bowel wall in rectal cancer specimens. Design: This was a secondary analysis of data from a prospective phase II study. Setting: This study was performed in a multiinstitutional setting. Patients: Included were 153 patients with stage II or stage III rectal cancer. Interventions: Patients were treated with chemoradiation and surgery. The surgical specimen tumor tissue was analyzed, and the distribution of residual cancer cells in each layer of the bowel wall was determined. Main Outcome Measures: Statistical analysis was used to examine the correlation of residual cancer cells in each layer of the bowel wall with the clinical/pathologic stage and tumor regression grade. Results: Forty-two of 153 (27%) patients had complete response in the bowel wall (ypT0). Of the remaining 111 patients who had residual cancer cells, 5 (3%) were ypTis, 12 (8%) were ypT1, 41 (27%) were ypT2, 50 (33%) were ypT3, and 3 (2%) were ypT4. Of the 94 patients with ypT2-4 tumors, 12 (13%) had cancer cells in the mucosa, and 53 (56%) had cancer cells in the submucosa; 92 (98%) had cancer cells in the muscularis propria. Pretreatment cT correlated with the distribution of residual cancer cells. Tumor regression grade was not associated with the distribution of residual cancer cells after chemoradiation. Limitations: Patients received different chemotherapy regimens. Conclusions: Residual cancer cells in rectal cancer specimens after chemoradiation are preferentially located close to the invasive front. This should be considered when designing strategies to diagnose complete pathologic response and when investigating the mechanisms of tumor resistance to chemoradiation.