Steroid Hormone Biosynthesis Metabolism Is Associated With Fatigue Related to Androgen Deprivation Therapy for Prostate Cancer

BackgroundAndrogen deprivation therapy (ADT) is a cornerstone treatment for prostate cancer. Despite the clinical benefits, ADT is associated with multiple adverse effects including fatigue. The goal of the study was to examine metabolomic changes to better understand cancer-related fatigue specific to ADT treatment.MethodsA total of 160 plasma samples collected from participants with (+ADT, n = 58) or without neoadjuvant ADT (−ADT, n = 102) prior to radiation therapy for treatment of non-metastatic localized prostate cancer were included in the study. Fatigue and sleep-related impairment were measured using the Patient Reported Outcomes Measurement Information System. Plasma metabolites were identified and measured using untargeted ultrahigh-performance liquid chromatography/mass spectrometry metabolomics analyses. Partial least square discriminant analysis was used to identify discriminant metabolite features, and the diagnostic performance of selected classifiers was quantified using AUROC curve analysis. Pathway enrichment analysis was performed using metabolite sets enrichment analyses.FindingsSteroid hormone biosynthesis pathways, including androstenedione metabolism as well as androgen and estrogen metabolism, were overrepresented by metabolites that significantly discriminated samples in the +ADT from the −ADT group. Additional overrepresented metabolic pathways included amino acid metabolism, glutathione metabolism, and carnitine synthesis. Of the metabolites that were significantly different between the groups, steroid hormone biosynthesis metabolites were most significantly correlated with fatigue severity. Sleep-related impairment was strongly correlated with fatigue severity and inversely correlated with ADT-induced reduction in androsterone sulfate.ConclusionsPatients with non-metastatic prostate cancer receiving neoadjuvant ADT prior to radiation therapy reported relatively more severe fatigue. Increased fatigue in this population may be attributable to sleep-related impairment associated with alterations in steroid hormone biosynthesis. Findings in this study provide a basis for further research of changes in sleep patterns and their role in this specific subcategory of cancer-related fatigue caused by the treatment.

Download Full-text

Abstract 28: Steroid Hormone Biosynthesis Metabolism Is Associated with Fatigue Related to Androgen Deprivation Therapy for Prostate Cancer

10.1158/1538-7755.asgcr21-28 ◽

2021 ◽

Author(s):

Hannah Allen ◽

Li Rebekah Feng ◽

Leorey Saligan

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Steroid Hormone ◽

Androgen Deprivation ◽

Steroid Hormone Biosynthesis ◽

Hormone Biosynthesis

Download Full-text

Faculty Opinions recommendation of Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.719895455.793514259 ◽

2016 ◽

Author(s):

Badrinath Konety

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Androgen Deprivation Therapy ◽

Advanced Prostate Cancer ◽

Locally Advanced ◽

Androgen Deprivation ◽

Phase 3 ◽

Locally Advanced Prostate Cancer

Download Full-text

Prostatic Artery Embolization Obviates the Need for Androgen Deprivation Therapy prior to Stereotactic Body Radiation Therapy in Prostate Cancer

Journal of Vascular and Interventional Radiology ◽

10.1016/j.jvir.2019.04.038 ◽

2019 ◽

Vol 30 (10) ◽

pp. 1635-1637

Author(s):

Diane Szaflarski ◽

Miltiadis Tembelis ◽

Aaron Katz ◽

Jonathan Haas ◽

Jason C. Hoffmann

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Androgen Deprivation Therapy ◽

Stereotactic Body Radiation Therapy ◽

Androgen Deprivation ◽

Artery Embolization ◽

Prostatic Artery Embolization ◽

Stereotactic Body Radiation ◽

Prostatic Artery

Download Full-text

Radiation therapy dose and androgen deprivation therapy in localized prostate cancer: a meta-regression of 5-year outcomes in phase III randomized controlled trials

Prostate Cancer and Prostatic Diseases ◽

10.1038/s41391-021-00432-2 ◽

2021 ◽

Author(s):

Tommy Jiang ◽

Daniela Markovic ◽

Jay Patel ◽

Jesus E. Juarez ◽

Ting Martin Ma ◽

...

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Androgen Deprivation Therapy ◽

Dose Escalation ◽

Low Dose ◽

Androgen Deprivation ◽

Phase Iii ◽

Localized Prostate Cancer ◽

Treatment Intensification ◽

Meta Regression

Abstract Background While multiple randomized trials have evaluated the benefit of radiation therapy (RT) dose escalation and the use and prolongation of androgen deprivation therapy (ADT) in the treatment of prostate cancer, few studies have evaluated the relative benefit of either form of treatment intensification with each other. Many trials have included treatment strategies that incorporate either high or low dose RT, or short-term or long-term ADT (STADT or LTADT), in one or more trial arms. We sought to compare different forms of treatment intensification of RT in the context of localized prostate cancer. Methods Using preferred reporting items for systemic reviews and meta-analyses (PRISMA) guidelines, we collected over 40 phases III clinical trials comparing different forms of RT for localized prostate cancer. We performed a meta-regression of 40 individual trials with 21,429 total patients to allow a comparison of the rates and cumulative proportions of 5-year overall survival (OS), prostate cancer-specific mortality (PCSM), and distant metastasis (DM) for each treatment arm of every trial. Results Dose-escalation either in the absence or presence of STADT failed to significantly improve any 5-year outcome. In contrast, adding LTADT to low dose RT significantly improved 5-year PCSM (Odds ratio [OR] 0.34, 95% confidence interval [CI] 0.22–0.54, p < 0.001) and DM (OR 0.35, 95% CI 0.20–0.63. p < 0.001) over low dose RT alone. Adding STADT also significantly improved 5-year PCSM over low dose RT alone (OR 0.55, 95% CI 0.41–0.75, p < 0.001). Conclusion While limited by between-study heterogeneity and a lack of individual patient data, this meta-analysis suggests that adding ADT, versus increasing RT dose alone, offers a more consistent improvement in clinical endpoints.

Download Full-text