Impact of “poorly differentiated clusters” in primary lesion as a novel prognostic indicator in colorectal liver metastasis.

3625 Background: Preoperative predictors for survival are needed in colorectal liver metastasis in order to select poor-risk group that truly requires perioperative chemotherapy. This study aimed to elucidate survival predictors in patients undergoing curative hepatectomy for colorectal liver metastasis, particularly focusing on the impact of poorly differentiated clusters (PDC); a novel histologic grading system in primary lesion. Methods: A total of 424 consecutive patients undergoing curative resection of both primary colorectal cancers and metastatic liver lesions at two referral centers were enrolled in the study. Determinants of overall survival (OS) and recurrence free survival (RFS) after hepatectomy were investigated by univariate and multivariate analysis, using detailed clinicopathological parameters in primary and metastatic lesions. Cancer clusters of ≥5 cancer cells and lacking a gland-like structure were counted under a x20 objective lens in a field containing the highest number of clusters at invasive front of primary lesions, and tumors with <5, 5 to 9, and ≥10 clusters were classified as PDC grade (G)1, G2 and G3, respectively (n=65, 132, and 227 tumors, respectively). Results: OS and RFS at 3 years were 59% and 27%, respectively, with average follow up period of 43 months. PDC grade in primary lesion was strongly associated with both 3-year-OS (83%, 62%, and 51%, respectively, p<0.0001) and 3-year-RFS (55%, 30%, and 17%, respectively, p<0.0001). Multivariate analysis revealed that PDC grade in primary lesion was the most potent prognostic factor after hepatectomy independent of T and N of primary lesion and size of liver metastasis. Conclusions: PDC grade in primary lesion is a novel potent prognostic indicator in colorectal liver metastasis, which is independent of T and N. It is noteworthy that PDC grade can bias the survival in clinical studies targeting perioperative chemotherapy in colorectal liver metastasis.