Impact of Negative Lymph Node Harvest on Overall Survival for Pathologic T4N0 Colon Cancer
Vanessa M. Welten, Adam C. Fields, Annabelle Jones, Nelya Melnitchouk, James Yoo, Jennifer Irani, Ronald Bleday, Joel E. Goldberg
Brigham and Women's Hospital, Boston, Massachusetts, United States
Objective: Adjuvant chemotherapy is recommended for patients with pT4N0 colon cancer. A minimum of 12 lymph nodes must be sampled for complete pathologic staging. We aimed to examine survival in patients with low-risk and high-risk pT4N0 colon cancer with increasing numbers of harvested negative lymph nodes to understand if chemotherapy could be eliminated in patients with a higher lymph node harvest.
Design: Retrospective cohort study utilizing the National Cancer Database data from 2004 to 2016.
Patients: Colon cancer patients staged as pT4N0.
Main Outcome Measures: The primary outcome was overall survival with respect to receipt of chemotherapy in low-risk (low/moderate differentiation without lymphovascular invasion (LVI) and high-risk (poor differentiation with LVI) pT4N0 patients. Outcomes were assessed using log-rank tests and Cox proportional-hazard modeling.
Results: We identified 13,088 patients, of which 6,170 (47%) received chemotherapy. 11,427 (87%) had low-risk features and 1,661 (13%) had high-risk features, with no difference in receipt of chemotherapy between the groups (p=0.21). For both low-risk and high-risk patients, 5-year overall survival was better for patients who received chemotherapy compared to patients who did not (Low-risk: 64% vs. 44%, p< 0.001; High-risk: 47% vs. 28%, p<0.001). Five-year overall survival for low-risk pT4N0 patients who did not receive chemotherapy compared to those who did receive chemotherapy, stratified by number of negative nodes harvested is as follows: 26% vs. 49% (p<0.001) for <10 nodes, 40% vs. 61% (p<0.001) for 10-19 nodes, 50% vs. 67% (p<0.001) for 20-29 nodes, 55% vs. 73% (p<0.001) for 30-39 nodes, and 56% vs. 79% (p<0.001) for 40+ nodes (Figure 1a). 5-year overall survival for high-risk pT4N0 patients who did not receive chemotherapy compared to those who did receive chemotherapy, stratified by number of negative nodes harvested is as follows: 10% vs. 19% (p<0.001) for <10 nodes, 25% vs 44% (p<0.001) for 10-19 nodes, 35% vs 55% (p<0.001) for 20-29 nodes, 31% vs 61% (p=0.0003) for 30-39 nodes, and 27% vs. 61% (p=0.01) for 40+ nodes (Figure 1b).
Conclusions: Though guidelines recommend adjuvant chemotherapy for pT4N0 colon cancer, less than half of patients in our study received chemotherapy. Patients with pT4N0 colon cancer demonstrated improved survival with chemotherapy, regardless of low-risk or high-risk pathology. This effect was not ameliorated by a greater lymph node harvest. In pT4N0 disease, there may be a higher chance of peritoneal spread given depth of tumor invasion. Thus, increasing the number of negative lymph nodes harvested does not mitigate the risk of recurrence and thereby increased mortality when compared to patients receiving chemotherapy. Our study confirms that all pT4N0 patients benefit from adjuvant chemotherapy irrespective of the number of harvested lymph nodes.
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