Is There An Association Between Use Of Androgen Deprivation Therapy And Acute Kidney Injury In Prostate Cancer Patients Treated With Definitive Radiotherapy?

Abstract

Androgen Deprivation Therapy (ADT) has been demonstrated to improve survival in men with prostate cancer undergoing definitive radiotherapy. However, ADT may have deleterious effects on cardiovascular, metabolic, bone, and mental health. Little is known about possible effects of ADT on renal function. Recent observational studies have demonstrated an association between ADT use and Acute Kidney Injury (AKI). These studies have included heterogeneous populations undergoing a variety of treatments, which may predispose to selection bias, and do not reflect recent changes in the definition of AKI. We sought to investigate the incidence of AKI in a large cohort of US veterans receiving definitive radiotherapy +/- ADT for prostate cancer. We investigated the prevalence of AKI through the Veterans Affairs Informatics and Computing Infrastructure (VINCI) platform. Our cohort consists of 44,246 veterans diagnosed with nonmetastatic prostate cancer between January 1st 2001 and October 31st 2015. All were treated with definitive radiotherapy. Exposure was defined as initiation of ADT within one year of diagnosis. The primary outcome was the incidence of AKI, defined via ICD codes. Covariates included in the multivariable regression model were: Age, Charlson Comorbidity Index score, race, smoking status, region, income, education, marital status, and year of diagnosis. Within the study population, 16,275 patients (37%) received RT+ADT and 27,971 (62%) received RT alone. With a median follow up of 6.8 years, there were 3,853 patients diagnosed with an AKI during the study period including 1,753 ADT users (10.8%) and 2,100 non-ADT users (7.5%). The overall cumulative incidence of AKI at 10 years was 11.4% including 14.1% for ADT users and 9.8% for non-ADT users. In the multivariable competing risks model, there was a significant association between ADT and AKI (subdistribution hazard ratio (SHR) = 1.28, 95% CI = 1.20-1.37, p<0.01). The use of ADT was associated with an increased risk of AKI in a large, modern cohort of US veterans undergoing definitive radiotherapy for prostate cancer. These findings warrant prospective confirmation, but suggest that renal function may be an important consideration when assessing the risks and benefits of ADT use. Further study will be useful to investigate if particular subgroups of patients receiving ADT are more susceptible to AKI and if the increased rate of AKI is associated with any long-term effects on renal function.