Distribution of Residual Cancer Cells in the Bowel Wall After Neoadjuvant Chemoradiation in Patients With Rectal Cancer

Abstract

Background The standard treatment for locally advanced rectal cancer is pre-operative chemoradiation 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 To determine the distribution of residual cancer cells in each layer of the bowel wall in rectal cancer specimens. Design Prospective Phase II study. Setting Multi-institutional. Patients 153 patients with stage II or stage III rectal cancer. Interventions Patients were treated with chemoradiation and surgery. 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/pathological 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 stage correlated with distribution of residual cancer cells. Tumor regression grade was not associated with 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.

Residual Esophageal Cancer after Neoadjuvant Chemoradiotherapy Frequently Involves the Mucosa and Submucosa

“…It might seem logical and self-evident that in the mucosa (and submucosa), being the presumed point of origin of both squamous cell carcinomas and adenocarcinomas of the esophagus, the largest amount of residual tumor was found. Interestingly, however, a recent study that looked at the distribution of residual rectal cancer cells within the bowel wall after nCRT 40 opposite from ours. They describe the preferential clearing of residual cancer cells from both the mucosa and the submucosa and report the highest percentage of residual cancer cells near the invasive front.…”

Flattened Tumor Requires a More Careful Attention for Residual Distal Cancer Spread in Locally Advanced Lower Rectal Carcinoma after Chemoradiotherapy

“…In all cases, the residual cancer was located close to the invasive front of the lesion, and in contrast, no case in which the residual cancer was limited to the superficial layer was found. Although the reason for this phenomenon is unclear, similar findings have been reported previously [23]. We thought that this discrepancy of the pre-CRT effect between the superficial and deeper layers could cause the difference in distribution of RDCS according to the macroscopic appearance of the tumor in this study.…”

Simultaneous integrated protection

“…Such a pattern was described in rectal cancer after neoadjuvant therapy and resection [4, 10]. Epithelial mesenchymal transition (EMT) was described to be more prevalent in residual tumor subvolumes at the invasion front [4] which in turn was described to be enriched for cancer stem cells [2].…”