Nontumor related risk score: A new tool to improve prediction of prognosis after hepatectomy for colorectal liver metastases

Background: Prognostic stratification of patients with colorectal cancer liver metastasis based solely on tumor-related factors has only moderate discriminatory ability. We hypothesized that the inclusion of nontumor related factors can improve prediction of long-term prognosis of patients with colorectal cancer liver metastasis. Methods: Nontumor related laboratory markers were assessed utilizing a training cohort from 2 U.S. institutions (n = 1,205). Factors independently associated with prognosis were used to develop a nontumor related prognostic score. The discriminatory ability, assessed by Harrell's C-statistics (C-index) and net reclassification improvement, was validated and compared with 3 commonly used tumor-related clinical risk scores: Fong clinical risk scores, m-clinical risk scores, and Genetic and Morphological Evaluation (GAME) score in an external validation cohort from 5 Asian (n = 1,307) and 3 European (n = 1,058) institutions. The discriminatory ability of nontumor related prognostic score combined with each of these 3 tumor-related prognostic scores was also estimated. Results: Alkaline phosphatase (hazard ratio 1.43; 95% confidence interval, 1.11–1.84), albumin (hazard ratio 0.71; 95% confidence interval, 0.57–0.89), and mean corpuscular volume (hazard ratio 19.0, per log unit; 95% confidence interval, 4.79–75.0) were each independently associated with increased risk of death after resection of colorectal cancer liver metastasis (all P < .05). In turn, alkaline phosphatase, albumin, and mean corpuscular volume were combined to form a nontumor related prognostic score (2.942 × mean corpuscular volume + 0.399 × alkaline phosphatase-0.339 × albumin-12) × 10 (median, 16; range, 1–30). The nontumor related prognostic score had good-to-modest discriminatory ability in the external cohort (C-index = 0.58), which was comparable to the 3 established tumor-related prognostic scores (C-index: Fong clinical risk scores, 0.53, m-clinical risk scores, 0.55, GAME, 0.58). The addition of the nontumor related prognostic score to the tumor-related prognostic scores enhanced the discriminatory ability in the entire study cohort (C-index: nontumor related score+Fong, 0.60, nontumor related score+m-clinical risk scores, 0.61, nontumor related score+GAME, 0.64), as well reclassification improvement (42.5, 42.7%, and 21.2%, respectively). Conclusion: Nontumor related prognostic information may help improve the prognostic stratification of patients after resection of colorectal cancer liver metastasis. The nontumor related prognostic score may be combined with tumor-related prognostic tools to enhance prognostic stratification of patients with colorectal cancer liver metastasis.