Association between peri-operative red blood cell transfusion and cancer recurrence in patients undergoing major cancer surgery: an umbrella review

Introduction: Peri-operative allogeneic red blood cell transfusion is hypothesised to increase the risk of cancer recurrence following cancer surgery. However, previous data supporting this association are limited by residual confounding. We conducted an umbrella review (i.e. a systematic review of systematic reviews) to synthesise and evaluate the evidence between red blood cell transfusion and cancer recurrence.

Methods: We searched online databases for systematic reviews of red blood cell transfusion and cancer-related outcomes. The AMSTAR 2 tool was used for quality assessment. The adequacy of confounding adjustment was judged according to a consensus-derived framework.

Results: We included five relevant systematic views which included patient populations ranging from 2110 to 184,190. Two reviews reported cancer recurrence, and all reported an association with red blood cell transfusion. Three reviews reported positive associations between red blood cell transfusion and adverse outcomes including all-cause mortality, recurrence-free survival and cancer-related mortality. According to AMSTAR 2, four reviews were rated as 'critically low quality' and one as 'low quality'. There was variation in how systematic reviews assessed the risk of bias from confounding. Compared with our pre-derived framework, we found a high likelihood of unmeasured confounding.

Discussion: Currently available evidence describes an association between peri-operative red blood cell transfusion and cancer recurrence, but this is mostly of low to critically low quality, with minimal control for residual confounding. Further research, at low risk of bias, is required to provide definitive evidence and inform practice.