Epidemiology of Complications After Solid Organ Transplantation - EpCOT Study

Overview

Cancer remains a major cause of morbidity and mortality post solid organ transplantation. While mortality from the other leading causes of death post-transplantation (e.g. cardiovascular disease and infection) is declining, mortality from cancer post-transplantation is increasing (1). This is due to both general and transplant-specific risk factors that combine to increase risk for cancer compared to the general population. However, there is a shortage of research exploring cancer epidemiology post solid organ transplantation in the UK. This is essential to guide clinicians and for counseling patients regarding expectations and outcomes after developing cancer post-transplantation. This is especially important as the aetiology, pathophysiology and outcomes of cancer post-transplantation may differ from the general population. Available data registries in the UK separately contain valuable cancer and transplant-specific data that can be combined to explore cancer epidemiology post-transplantation more comprehensively, which can be directly translated into patient benefit by utilizing transplant-specific data (rather than translating from general population or non-UK patient demographics). The purpose of this project is to combine existing data resources to link up the complete patient journey for solid organ transplant recipients and focus on the entire spectrum of cancer from incidence to mortality. In addition, we can use this linked dataset to explore many non-cancer related complications after solid organ transplantation. This will help us better understand the complete burden of disease after transplantation (which may be competing risks for development of cancer) and help improve delivery of effective post-transplant care for UK solid organ transplant patients.

Solid organ transplantation is associated with an increased incidence of cancer versus the general population, and broadly on par with comparable immune deficiency states such as HIV/AIDS. The aetiology of cancer post-transplantation is primarily due to the burden of immunosuppression that is compulsory for all transplant patients to prevent allograft rejection. Skewed standardised incidence ratios are observed for cancer post-transplantation compared to the general population, with preponderance for cancers with a strong viral component. The literature on cancer-related mortality after transplantation is scarce, but again disparate mortality risk has been documented comparing solid organ transplant recipients to the general population. There is a shortage of UK-specific data to guide transplant clinicians on how best to deal with cancer. This is important as countries differ with regards to ethnic demographics and post-transplant immunosuppression protocols, both of which are important confounders to translate data from other transplant cohorts. Collett and colleagues have previously published registry data of cancer incidence in British transplant recipients (by linking UK Transplant Registry to various national cancer registries) for a cohort transplanted between 1980 and 2007. They found similarities but also important differences between cancer incidence in a British solid organ recipient cohort versus registry data from Sweden, Finland, Canada and the United States. Importantly, the relevance of this data to the contemporary solid organ transplant cohort is unclear, as immunosuppression protocols have evolved since 2007 to a predominantly tacrolimus-based regimen since publication of the SYMPHONY study in 2007. No subsequent analysis has been done to determine the impact of tacrolimus introduction into cancer occurrence post-transplantation in the UK. Our group has previously published the first analysis of cancer-related mortality in the UK, providing data on site of cancer-related mortality and stratifying analysis along demographic factors such as age, gender and/or ethnicity that are relevant to the British population. This analysis linked two different national data resources from the study by Collett and colleagues - Hospital Episode Statistics and the Office for National Statistics. It demonstrated the crude cancer-related mortality rate in England (between 2001 and 2012) was 361 cancer-related deaths per 100,000 person years (compared to 424 and 416 for cardiovascular- and infection-related deaths respectively). Of note, we have also observed cancer-related mortality within the first year post kidney transplantation (7.4%) rises in incidence with increasing time post-transplantation (22.0% beyond the first year post kidney transplantation and second leading cause of death). Our previous experience has identified the strengths and limitations of utilising such data resources. One of the major limitations with registry data is the absence of important and relevant information that can confound the data, which can be overcome by linking data between registries. For example, in our previous analysis we identified kidney cancer accounted for over half of all cancer-related mortality for kidney transplant recipients with a history of pre-transplant cancer. However, the limitation of our data was we were unable to probe this association further and ascertain a number of important issues; 1) location of kidney cancer (whether native or transplant kidney), 2) whether pre-transplant cancer was kidney-related, and 3) time on dialysis pre-transplant (which is a strong risk factor for acquired cystic renal disease and malignant transformation). While this information was unavailable in our data sets, such information is contained within other national data resources. Data or record linkage has been defined as "a process of pairing records from two files and trying to select the pairs that belong to the same entity." Cancer data is not routinely collated by transplant centers and there is no robust mechanism to explore cancer epidemiology data post solid organ transplantation through the UK Transplant Registry. However, linking information to other existing data registry resources will facilitate such analysis. This is an under-researched area within both transplant and cancer communities, but increasingly important due to the increasing incidence and prevalence of cancer post solid organ transplantation.