Prognostic value of poorly differentiated clusters in the primary tumor in patients undergoing hepatectomy for colorectal liver metastasis

This study aimed to determine the prognostic value of a novel grading system based on the histologic assessment of poorly differentiated clusters (PDCs) in the primary lesions in patients with hepatectomy for colorectal liver metastasis (CRLM). Preoperative survival predictors for CRLM are required to determine candidates for perioperative chemotherapy who would otherwise have a poor prognosis.In total, 411 consecutive patients undergoing curative resection of primary colorectal cancers and metastatic liver lesions at 2 institutions were enrolled. Cancer clusters comprising ≥ 5 cancer cells, lacking a gland-like structure, were defined as PDCs and quantifiably graded.According to PDCs, 65, 127, and 219 patients were classified as being grades (G)1, G2, and G3, respectively. PDCs were associated with T and N stages and tumor budding in primary tumor, extrahepatic disease, and serum CEA levels (P ≤ .0001-.045), but not with the number and size of liver metastasis. PDC grade significantly influenced recurrence rate in extrahepatic sites, including the lung and peritoneum (P.0001). The 2-year disease-free survival after hepatectomy was 64.6%, 38.8%, and 22.4% in G1, G2, and G3, respectively. Based on multivariate analysis, PDC grade was selected as an independent prognostic factor together with other conventional factors such as extrahepatic disease and the number of liver metastasis.PDC grade in primary lesions is a novel potent prognostic indicator in CRLM independent of the anatomic extent of disease. Notably, PDC grade can bias survival rates in clinical studies targeting perioperative chemotherapy in CRLM.