Published online Feb 27, 2020. doi: 10.4240/wjgs.v12.i2.34
Peer-review started: September 27, 2019
First decision: October 24, 2019
Revised: November 24, 2019
Accepted: December 14, 2019
Article in press: December 14, 2019
Published online: February 27, 2020
Processing time: 110 Days and 16.4 Hours
Liver metastases develop in 25%-30% of patients with colorectal cancer and one-quarter undergo surgical resection, the gold standard treatment, to achieve 5-year survival of 40%-50%. Unresected colorectal liver metastases carry a poor median survival of 3-20 mo. Further recurrences develop in 60% of patients after liver resection and median survival is only 8-10 mo if these are left untreated. Despite available multimodal treatment options, colorectal liver metastases still carry a poor prognosis and effective new treatment strategies are desirable.
There is a growing interest in chemopreventive agents to halt carcinogenesis. Developing new drugs is costly and so it is attractive to repurpose existing drugs for use as chemopreventive agents. Statins have been investigated for anti-tumour effects in other gastrointestinal cancers. Statin therapy has never been previously investigated as chemoprevention for colorectal liver metastases.
The main objective of this study was to was assess whether Statins can serve as chemoprevention for colorectal liver metastases by evaluating the effect of Statin therapy on the histopathology of resected colorectal liver metastases and on the outcome of patients after resection of colorectal liver metastases.
We included all patients who underwent primary hepatic resection for colorectal liver metastases with curative intent between 2005 and 2017 as identified using our institution’s prospectively maintained database. We analysed data on patient demographics, statin therapy usage, liver resection, histopathology of colorectal liver metastases, and patients’ clinical outcome.
Out of 586 patients who underwent resection of colorectal liver metastases at a median age of 68 (19-88) years, 181 patients used Statin therapy. During median follow-up time of 23 (12-96) mo, recurrent colorectal cancer metastases developed in 267 patients and a total of 131 patients died. Six independent predictors of poorer disease-free survival identified by multi-variate analysis were synchronous presentation, multiple tumours, tumour size ≥ 5 cm, moderate–severe steatosis, peri-neural invasion, and R1-resection margin. Four independent predictors of poorer overall survival identified by multi-variate analysis were the use neo-adjuvant chemotherapy, major hepatectomy, peri-neural invasion and R1-resection margin. Statin therapy did not affect histo-pathological or radiological traits of resected colorectal liver metastases, and did not affect patient outcomes.
The study did not find any association between Statin therapy and the characteristics of resected colorectal liver metastases or patient survival following resection. This suggests that Statin therapy does not modulate tumour biology of resected colorectal liver metastases.
Our study shows Statins do not affect resected colorectal liver metastases or patient outcomes following resection. The routine use of Statins as chemoprevention cannot be justified in this patient group. However, our study only focused on resected colorectal metastases. Future studies would need to also assess the effect of Statin therapy on non-resected colorectal liver metastases and on the outcome of these patients who do not undergo liver resection. Future studies will also need to assess the effect of specific Statins on colorectal liver metastases.