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
Above and beyond their role in cardiovascular risk reduction, statins appear to have a chemopreventive role in some gastro-intestinal cancers. In the quest for new chemopreventive agents, some existing established drugs such as statins have shown potential for re-purposing as chemoprevention. Probing existing drugs, whose pharmacodynamics are familiar, for novel beneficial effects offers a more cost-effective and less time-consuming strategy than establishing brand new drugs whose pharmacodynamic profile is unfamiliar. Observational studies show statins decrease the risk of developing colorectal cancer but there are no published studies exploring the potential impact of statins on carcinogenesis in colorectal liver metastases (CRLM).
To evaluate impact of statins on outcomes of CRLM resection, and secondarily to assess if statins influence CRLM histo-pathology.
We conducted a retrospective cohort study of patients operated for CRLM over a 13-year period from 2005 to 2017. Patients were identified from a prospective database maintained in our Tertiary care hospital. All 586 patients included the study had undergone resection of CRLM following discussion at multidisclipinary team meeting, some patients requiring neoadjuvant chemotherapy to downstage CRLM prior to surgery. We analysed patient demographics, operative details, CRLM histopathology, Index of Deprivation, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and chemotherapy use in relation to clinical outcome. Statistics were performed using SPSS version 16.0; significance taken at 5%.
Liver resection for CRLM was undertaken in 586 patients at a median age of 68 (range 19 to 88) years. Statin therapy was used by 181 patients. Median follow-up time was 23 (range 12-96) mo and further colorectal cancer metastases developed in 267 patients. A total of 131 patients died. Multi-variate analysis identified 6 independent predictors of poorer disease-free survival: Synchronous presentation, multiple tumours, tumour size ≥ 5 cm, moderate–severe steatosis, peri-neural invasion, and R1-resection margin. Poorer overall survival was significantly associated with neo-adjuvant chemotherapy, major hepatectomy, peri-neural invasion and R1-resection margin. Neither histo-pathological nor radiological traits of CRLM were affected by statins, and, there was no demonstrable effect of statin therapy on patient outcomes.
Statin therapy does not affect patient survival following liver resection for CRLM. We postulate the reason for this key finding is that statins do not modulate tumour biology of CRLM.
Core tip: Colorectal liver metastases (CRLM) develop in 25%-30% of patients with colorectal cancer and disease prevalence has increased with expansion in the at-risk older age group. The need for chemoprevention to inhibit carcinogenesis is an attractive option that has shown promise in patients at high risk of developing CRLM. Observational studies have shown statins are promising chemopreventive agents but no data exist specifically for CRLM. Statins represent a well-established drug group whose pharmacodynamic properties are familiar to clinicians and if they demonstrate effectiveness as chemoprevention for CRLM, repurposing statins for this use will be more cost- and time- effective compared to developing new agents.