Adiposity and response to androgen signaling inhibition (ASI) in men with metastatic castration-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 72-72
Author(s):  
Andrew Warren Hahn ◽  
Rebecca Tidwell ◽  
Devaki Shilpa Surasi ◽  
Patrick Glen Pilie ◽  
Daniel Frigo ◽  
...  

72 Background: Improved understanding of how host factors influence the efficacy and toxicity of ASI could improve outcomes. Adiposity increases the risk for recurrence and lethal disease in men with localized prostate cancer. Few studies have evaluated the influence of adiposity in metastatic prostate cancer, and in these studies, adiposity was associated with improved outcomes, a potential “obesity paradox”. Herein, we assess whether adiposity is associated with response to maximal ASI in mCRPC and assess how individual body composition measurements interact to influence outcomes. Methods: Men with mCRPC uniformly treated on a prospective clinical trial with abiraterone acetate plus apalutamide were included in this post-hoc analysis (NCT02703623). Responders were defined as those with a decrease in PSA of > 50% after 8 weeks of therapy. Body composition was assessed at the level of L3 on baseline CT scan at trial registration using Slice-O-Matic version 5.0. Body composition indices were normalized for height (m2). Non-parametric Kruskal-Wallis test was used to evaluate associations between continuous baseline measures. A multivariable CART model was used to determine if baseline measures could divide patients into distinct risk groups. Results: In 186 men with mCRPC, responders to maximal ASI (n = 128) had higher subcutaneous adiposity (SATi, 79.3 vs. 67.6, p = 0.02), visceral adiposity (VATi, 76.4 vs. 61.5, p = 0.03), and body mass index (BMI, 30.3 vs. 29.2, p = 0.04). There was a strong correlation between BMI and SAT (r = 0.81). In exploratory multivariable modeling, BMI and VATi had the strongest associations with response to ASI. Specifically, men with a BMI ≥ 26.73 had a higher response rate (75% vs. 46%). For men with a BMI < 26.73, a VATi ≥ 24.7 enriched for response to therapy (86% vs. 26%). Conclusions: Elevated subcutaneous and visceral adiposity is associated with improved response to maximal ASI in men with mCRPC. In hypothesis-generating models, visceral adiposity had the strongest association with response to ASI in men with lower BMI. Further studies need to assess how and when adiposity becomes favorable for outcomes in advanced prostate cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5088-5088
Author(s):  
Ecaterina Ileana ◽  
Sami Antoun ◽  
Laurence Albiges ◽  
Christophe Massard ◽  
Mario Di Palma ◽  
...  

5088 Background: Abiraterone acetate (AA) and enzalutamide (MDV3100), two androgen receptor-directed compounds, have been shown to improve survival for patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after Docetaxel.. Since these drugs might be used at an early-stage in the future, and skeletal muscle (SM) and adipose tissue (AT) are known to be prognosis parameters, the aim of this study was to evaluate the body composition changes in patients with mCRPC treated with AA and MDV3100. Methods: Patients included in AFFIRM (n=62 treated with MDV3100 and placebo n=28) and COU-AA-301 (n=24 treated with AA+Prednisone (P)10mg/day and placebo+P n= 13) trials at the Institute Gustave Roussy were included in the analysis. Cross-sectional areas (cm2) of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and SM were assessed by computed tomography imaging at 3rd lumbar vertebra and were indexed for height (cm2/m2) with Slice-O-Matic software V4.3 at baseline, 3, 6 and 12 months of treatment. The data from patients treated with AA or MDV3100 were compared to placebo-patients and tissues changes were compared to baseline. We used the validated sarcopenic definitions as SM index less than 52.4 (cm2/m2). Results: For all cohort, median age was 69 years (range: 48-83), median weight was 79 kg (range: 47-150) and median BMI was 25.9 kg/m2(range: 18-46). At inclusion, 74 patients (58%) were overweight or obese (BMI>24.9 kg/m2), and only 2 patients were underweight (BMI<18.5kg/m2). 97 patients (81%) were sarcopenic, and 56 (75%) of overweight or obese patients were sarcopenic. Over 3 months, the patients from the entire cohort lost muscle mass (mean change: 4.5±7.5% (» 0.7 kg of muscle)) (P=0.01) . A non significant loss of SAT -4.6±19.2% and a non significant increase of VAT (+10.7±50.3% ) were observed. A similar pattern was observed at 6 months. There was no significant difference between body composition changes in treated groups and placebo. Conclusions: Sarcopenia is highly prevalent in patients with advanced CRPC. Unexpectedly, no difference in body composition changes was observed between patients treated with MDV3100 or AA and placebo.


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