Modern Chemotherapy Mitigates Adverse Prognostic Effect of Regional Nodal Metastases in Stage IV Colorectal Cancer

Background: In colorectal cancer, the involvement of regional lymph nodes with metastasis is an established prognostic factor. The impact of the number of positive nodes on patient outcome with stage IV disease is not well defined. Methods: A retrospective review was performed of 1,421 patients at two tertiary referral centers with stage IV colorectal cancer who underwent primary tumor resection. Associations between regional nodes, lymph node ratio (LNR), and overall survival (OS) from date of diagnosis were analyzed. Results: The number of positive regional nodes and LNR correlated with multiple sites of metastases (p < 0.001). Survival was significantly associated with the number of positive nodes and LNR, with a median OS of 43 months with negative nodes, compared to 20 months with ≥7 positive nodes (p < 0.001). The number of regional nodal metastases correlated with OS among 400 patients undergoing resection of liver metastases (p = 0.005) but lost prognostic significance in the subset of 223 patients who underwent hepatectomy with perioperative oxaliplatin- or irinotecan-based chemotherapy (p = 0.48). Conclusions: In stage IV colorectal cancer, an increasing number of positive regional nodes and LNR correlate with multiple sites of metastases and poorer survival. The number of metastatic regional lymph nodes loses prognostic significance with modern chemotherapy in patients undergoing resection of liver metastases.