Abstract
Purpose: Androgen deprivation therapy (ADT) is a common and effective treatment for prostate cancer. However, multiple adverse effects such as fatigue are associated with this therapy. The purpose of this study was to characterize the metabolic profile associated with cancer-related fatigue specific to ADT.
Methods: 160 participants with non-metastatic prostate cancer who were receiving (+ADT, n = 58) or were not receiving neoadjuvant ADT (-ADT), n = 102) before undergoing radiotherapy were included in this study. Plasma samples were taken from all participants, and metabolites were identified and quantified using ultrahigh performance liquid chromatography/mass spectrometry. Partial least square discriminant analysis was used to identify discriminant metabolite features, and diagnostic performance of selected classifiers was quantified using AUROC curve analysis. Pathway enrichment analysis was performed using metabolite sets enrichment analyses.
Results: Particular metabolic pathways were found to be significantly over-represented in the +ADT group compared to the -ADT group, thereby creating a distinct metabolic profile associated with each group. These pathways were steroid hormone biosynthesis pathways, including androstenedione metabolism and androgen and estrogen metabolism, as well as amino acid metabolism, glutathione metabolism, and carnitine synthesis. Of all these pathways, steroid hormone biosynthesis was most significantly correlated with fatigue severity. It was also found that sleep-related impairment was highly correlated with severity of fatigue and inversely correlated with ADT-induced reduction in androsterone sulfate.
Conclusion: Individuals who received ADT reported significantly higher levels of fatigue. This finding may be due to sleep-related impairment associated with changes in steroid hormone biosynthesis. This result paves the way for future research on cancer-related fatigue and changes in sleep patterns due to alterations in steroid hormones. It may also help patients and clinicians make a more precise cost-benefit analysis when deciding on a prostate cancer treatment plan.
Citation Format: Hannah Allen, Li Rebekah Feng, Leorey Saligan. Steroid Hormone Biosynthesis Metabolism Is Associated with Fatigue Related to Androgen Deprivation Therapy for Prostate Cancer [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 28.
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