Sirolimus effects on cancer incidence after kidney transplantation: a meta-analysis

Sirolimus, an immunosuppressant option for kidney transplant recipients, may reduce cancer risk by interrupting the mammalian target of rapamycin pathway. However, studies of sirolimus and cancer incidence in kidney recipients have not been definitive, and have had limited ability to examine specific cancer types. The literature was systematically reviewed to identify randomized controlled trials (RCTs) and observational studies of kidney recipients that compared sirolimus users to sirolimus nonusers. Meta-analytic methods were used to obtain pooled estimates of the association between sirolimus use and incidence of total cancer and specific cancer types. Estimates were stratified by study type (RCT vs. observational) and use of cyclosporine (an immunosuppressant that affects DNA repair). Twenty RCTs and two observational studies were eligible for meta-analysis, including 39,039 kidney recipients overall. Sirolimus use was associated with lower overall cancer incidence (incidence rate ratio [IRR]=0.71, 95% CI=0.56-0.90), driven by a reduction in incidence of nonmelanoma skin cancer (NMSC, IRR=0.49, 95% CI=0.32-0.76). The protective effect of sirolimus on NMSC risk was most notable in studies comparing sirolimus against cyclosporine (IRR=0.19, 95% CI=0.04-0.84). After excluding NMSCs, there was no overall association between sirolimus and incidence of other cancers (IRR=1.06, 95% CI=0.69-1.63). However, sirolimus use had associations with lower kidney cancer incidence (IRR=0.40, 95% CI=0.20-0.81), and higher prostate cancer incidence (IRR=1.85, 95% CI=1.17-2.91). Among kidney recipients, sirolimus users have lower NMSC risk, which may be partly due to removal of cyclosporine. Sirolimus may also reduce kidney cancer risk but did not appear protective for other cancers, and it may actually increase prostate cancer risk.