Muscle Loss During Androgen Deprivation Therapy Is Associated With Higher Risk of Non-Cancer Mortality in High-Risk Prostate Cancer

Pai-Kai Chiang; Wei-Kung Tsai; Allen Wen-Hsiang Chiu; Jhen-Bin Lin; Feng-Yi Yang; Jie Lee

doi:10.3389/fonc.2021.722652

Muscle Loss During Androgen Deprivation Therapy Is Associated With Higher Risk of Non-Cancer Mortality in High-Risk Prostate Cancer

Front Oncol. 2021 Sep 17:11:722652. doi: 10.3389/fonc.2021.722652. eCollection 2021.

Authors

Pai-Kai Chiang^{1

2

3

4}, Wei-Kung Tsai^{2

3

4

5}, Allen Wen-Hsiang Chiu^{2

3}, Jhen-Bin Lin⁶, Feng-Yi Yang^{1

7}, Jie Lee^{3

8}

Affiliations

¹ Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Department of Urology, MacKay Memorial Hospital, Taipei, Taiwan.
³ Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
⁴ MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
⁵ PhD Program in Nutrition and Food Science, Graduate Institute of Biomedical and Pharmaceutical Science, Fu-Jen Catholic University, New Taipei City, Taiwan.
⁶ Department of Radiation Oncology, Changhua Christian Hospital, Changhua, Taiwan.
⁷ Biophotonics and Molecular Imaging Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁸ Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan.

Abstract

The changes in body composition are early adverse effects of androgen deprivation therapy (ADT); however, their prognostic impact remains unclear in prostate cancer. This study aimed to evaluate the association between body composition changes and survival in patients with high-risk prostate cancer. We measured the skeletal muscle index (SMI) and total adipose tissue index (TATI) at the L3 vertebral level using computed tomography at baseline and within one year after initiating ADT in 125 patients with high-risk prostate cancer treated with radiotherapy and ADT between 2008 and 2018. Non-cancer mortality predictors were identified using Cox regression models. The median follow-up was 49 months. Patients experienced an average SMI loss of 5.5% over 180 days (95% confidence interval: -7.0 to -4.0; p<0.001) and TATI gain of 12.6% over 180 days (95% confidence interval: 9.0 to 16.2; p<0.001). Body mass index changes were highly and weakly correlated with changes in TATI and SMI, respectively (Spearman ρ for TATI, 0.78, p<0.001; ρ for SMI, 0.27, p=0.003). As a continuous variable, each 1% decrease in SMI was independently associated with a 9% increase in the risk of non-cancer mortality (hazard ratio: 1.09; p=0.007). Moreover, the risk of non-cancer mortality increased 5.6-fold in patients with SMI loss ≥5% compared to those with unchanged SMI (hazard ratio: 5.60; p=0.03). Body mass index and TATI were not associated with non-cancer mortality. Muscle loss during ADT is occult, independent of weight change, and independently associated with increased non-cancer mortality in patients with high-risk prostate cancer.

Keywords: androgen deprivation therapy; body composition; non-cancer mortality; prostate cancer; sarcopenia; skeletal muscle loss.