Do statins really improve colorectal cancer-specific mortality?

Abstract

TO THE EDITOR: Cardwell et al 1 recently reported the impact of using statins on survival in patients with colorectal cancer in a population-based cohort study. The authors demonstrated that the use of statins after diagnosis was associated with a decreased risk in colorectal cancer–specific and all-cause mortality. We have some comments about the beneficial effect of statin use after colorectal cancer diagnosis. Before we comment that statins improve survival after colorectal cancer diagnosis, we should mention some confounding factors that affect survival. In the revised tumor node categorization of the American Joint Committee on Cancer staging (sixth edition) for colorectal cancer according to the National Survival Outcomes Data, the number of positive nodes and T stage affect survival significantly. 2 According to this revision, in patients with node-negative colorectal cancer, the 5-year overall survival (OS) rate was 87.5% for those with T3 tumors, whereas it was 79.6% and 58.4% for those with T4a and T4b tumors, respectively. In patients with stage III disease, the number of positive nodes can also affect survival for each T category. The 5-year OS rate was between 68.7% and 87.3% in patients with T1 to T2 node-positive disease, whereas it was between 19.7% and 68.7% in those with T3 to T4 node-positive disease. 2 However, there are no available data on T or N stage in the Cardwell et al 1 study. In addition, the authors stated that patients with colorectal cancer newly diagnosed between 1998 and 2009 were included in the cohort. In the study, 1 statin users were more likely to have been diagnosed recently, compared with statin nonusers. In 2004, oxaliplatin was approved by the US Food and Drug Administration for patients with stage III colon cancer, because of the significant OS and disease-free survival advantages shown in the international MOSAIC (Multicenter International Study of Oxaliplatin/Fluorouracil/Leucovorin in Adjuvant Treatment of Colon Cancer) trial. 3-5 Because there were more recently diagnosed patients in the statin-user group of the Cardwell et al study, oxaliplatin-based adjuvant treatments may have been administered at a higher rate among statin users compared with nonusers. Adjusted analyses were conducted according to year of diagnosis, chemotherapy receipt within 6 months, and cancer stage, which may have had a bias effect because of the missing data on T stage, N stage, and chemotherapeutic regimen subgroup. Furthermore, the presence of extranodal tumor deposits is significantly associated with worse OS in patients with node-negative stage III colorectal cancer. 6,7 Presence of perineural invasion (PNI) has also been associated with worse prognosis in several studies. Liebig et al 8 reported that the 5-year OS rate was 72% and 25% in patients with PNI-negative and PNI-positive colorectal cancer, respectively, and on multivariable analysis, PNI was found to be an independent prognostic factor for both colorectal cancer–specific OS and disease-free survival. Thus, the missing data about the distribution of positivity of PNI and extranodal tumor deposits may also have had a bias effect on survival outcome regarding statins. On these grounds, it would be interesting to know the distribution of prognostic markers such as T stage, N stage, chemotherapeutic regimen subgroup, PNI positivity, and presence of extranodal tumor deposits before commenting that statin use after diagnosis of colorectal cancer improves survival.