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Sarcopenia in Men with Bone-Predominant Metastatic Castration-Resistant Prostate Cancer Undergoing Ra-223 Therapy

Published:January 25, 2023DOI:https://doi.org/10.1016/j.clgc.2023.01.009

      Abstract

      Introduction

      Osteosarcopenia is the progressive loss of musculoskeletal structure and functionality, contributing to disability and mortality. Despite complex interactions between bone and muscle, osteosarcopenia prevention and treatment in men with metastatic castration-resistant prostate cancer (mCRPC) focuses predominantly on bone health. It is unknown whether Radium-223 (Ra-223) therapy affects sarcopenia.

      Methods

      We identified 52 patients with mCRPC who had received Ra-223 and had a baseline plus ≥1 follow-up abdominopelvic CT scan. The total contour area (TCA) and averaged Hounsfield units (HU) of the left and right psoas muscles were obtained at the inferior L3 endplate, and the Psoas Muscle Index (PMI) was calculated therefrom. Intra-patient musculoskeletal changes were analyzed across various time points.

      Results

      TCA and PMI gradually declined over the study period (p=0.002, p=0.003, respectively), but Ra-223 therapy did not accelerate sarcopenia, nor the decline of HU compared to the pre-Ra-223 period. The median overall survival of patients with baseline sarcopenia was numerically worse (14.93 versus 23.23 months, HR 0.612, p=0.198).

      Conclusions

      Ra-223 does not accelerate sarcopenia. Thus, worsening muscle parameters in men with mCRPC undergoing Ra-223 therapy are attributable to other factors. Further research is needed to determine whether baseline sarcopenia predicts poor overall survival in such patients.

      Micro-Abstract

      There are complex interactions between bone and skeletal muscle. However, the prevention and treatment of treatment-induced osteosarcopenia in men with metastatic castration-resistant prostate cancer focuses predominantly on bone health. In a single-center cohort of 52 patients we demonstrate that bone-targeted Radium-223 therapy does not accelerate sarcopenia, but baseline sarcopenia is associated with poor survival in such patients.
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      References

        • Body JJ
        • Casimiro S
        • Costa L.
        Targeting bone metastases in prostate cancer: improving clinical outcome.
        Nat Rev Urol. 2015; 12: 340-356
        • Parker C
        • Nilsson S
        • Heinrich D
        • Helle SI
        • O'Sullivan JM
        • Fossa SD
        • et al.
        Alpha emitter radium-223 and survival in metastatic prostate cancer.
        N Engl J Med. 2013; 369: 213-223
        • Smith M
        • Parker C
        • Saad F
        • Miller K
        • Tombal B
        • Ng QS
        • et al.
        Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial.
        Lancet Oncol. 2019; 20: 408-419
        • Kirk B
        • Zanker J
        • Duque G.
        Osteosarcopenia: epidemiology, diagnosis, and treatment-facts and numbers.
        J Cachexia Sarcopenia Muscle. 2020; 11: 609-618
        • Ryan AM
        • Prado CM
        • Sullivan ES
        • Power DG
        • Daly LE.
        Effects of weight loss and sarcopenia on response to chemotherapy, quality of life, and survival.
        Nutrition. 2019; 67-68110539
        • Coleman R
        • Hadji P
        • Body JJ
        • Santini D
        • Chow E
        • Terpos E
        • et al.
        Bone health in cancer: ESMO Clinical Practice Guidelines.
        Ann Oncol. 2020; 31: 1650-1663
        • Cruz-Jentoft AJ
        • Bahat G
        • Bauer J
        • Boirie Y
        • Bruyere O
        • Cederholm T
        • et al.
        Sarcopenia: revised European consensus on definition and diagnosis.
        Age Ageing. 2019; 48: 601
        • Fizazi K
        • Carducci M
        • Smith M
        • Damiao R
        • Brown J
        • Karsh L
        • et al.
        Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study.
        Lancet. 2011; 377: 813-822
        • Bonnet N
        • Bourgoin L
        • Biver E
        • Douni E
        • Ferrari S.
        RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass.
        J Clin Invest. 2019; 129: 3214-3223
        • Phu S
        • Bani Hassan E
        • Vogrin S
        • Kirk B
        • Duque G
        Effect of Denosumab on Falls, Muscle Strength, and Function in Community-Dwelling Older Adults.
        J Am Geriatr Soc. 2019; 67: 2660-2661
        • Suominen MI
        • Fagerlund KM
        • Rissanen JP
        • Konkol YM
        • Morko JP
        • Peng Z
        • et al.
        Radium-223 Inhibits Osseous Prostate Cancer Growth by Dual Targeting of Cancer Cells and Bone Microenvironment in Mouse Models.
        Clin Cancer Res. 2017; 23: 4335-4346
        • Mourtzakis M
        • Prado CM
        • Lieffers JR
        • Reiman T
        • McCargar LJ
        Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care.
        Appl Physiol Nutr Metab. 2008; 33: 997-1006
        • Ohtaka A
        • Aoki H
        • Nagata M
        • Kanayama M
        • Shimizu F
        • Ide H
        • et al.
        Sarcopenia is a poor prognostic factor of castration-resistant prostate cancer treated with docetaxel therapy.
        Prostate Int. 2019; 7: 9-14
        • Cheng S
        • Arciero V
        • Goldberg H
        • Tajzler C
        • Manganaro A
        • Kozlowski N
        • et al.
        Population-Based Analysis Of The Use Of Radium-223 For Bone-Metastatic Castration-Resistant Prostate Cancer In Ontario, And Of Factors Associated With Treatment Completion And Outcome.
        Cancer management and research. 2019; 11: 9307-9319
        • Ikeda T
        • Ishihara H
        • Iizuka J
        • Hashimoto Y
        • Yoshida K
        • Kakuta Y
        • et al.
        Prognostic impact of sarcopenia in patients with metastatic hormone-sensitive prostate cancer.
        Jpn J Clin Oncol. 2020; 50: 933-939
        • Cushen SJ
        • Power DG
        • Murphy KP
        • McDermott R
        • Griffin BT
        • Lim M
        • et al.
        Impact of body composition parameters on clinical outcomes in patients with metastatic castrate-resistant prostate cancer treated with docetaxel.
        Clin Nutr ESPEN. 2016; 13: e39-e45
        • Stangl-Kremser J
        • Suarez-Ibarrola R
        • Andrea D
        • Korn SM
        • Pones M
        • Kramer G
        • et al.
        Assessment of body composition in the advanced stage of castration-resistant prostate cancer: special focus on sarcopenia.
        Prostate Cancer Prostatic Dis. 2020; 23: 309-315
        • Iwamoto H
        • Kano H
        • Shimada T
        • Naito R
        • Makino T
        • Kadomoto S
        • et al.
        Sarcopenia and Visceral Metastasis at Cabazitaxel Initiation Predict Prognosis in Patients With Castration-resistant Prostate Cancer Receiving Cabazitaxel Chemotherapy.
        In vivo. 2021; 35: 1703-1709
        • Alibhai SMH
        • Zukotynski K
        • Walker-Dilks C
        • Emmenegger U
        • Finelli A
        • Morgan SC
        • et al.
        Bone Health and Bone-targeted Therapies for Prostate Cancer: a Programme in Evidence-based Care - Cancer Care Ontario Clinical Practice Guideline.
        Clin Oncol (R Coll Radiol). 2017; 29: 348-355
        • Dennison EM
        • Sayer AA
        • Cooper C.
        Epidemiology of sarcopenia and insight into possible therapeutic targets.
        Nat Rev Rheumatol. 2017; 13: 340-347
        • Cruz-Jentoft AJ
        • Baeyens JP
        • Bauer JM
        • Boirie Y
        • Cederholm T
        • Landi F
        • et al.
        Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People.
        Age Ageing. 2010; 39: 412-423
        • Pezaro C
        • Mukherji D
        • Tunariu N
        • Cassidy AM
        • Omlin A
        • Bianchini D
        • et al.
        Sarcopenia and change in body composition following maximal androgen suppression with abiraterone in men with castration-resistant prostate cancer.
        Br J Cancer. 2013; 109: 325-331
        • Sartor O
        • de Bono JS.
        Metastatic Prostate Cancer.
        N Engl J Med. 2018; 378: 645-657
        • Ebadi M
        • Wang CW
        • Lai JC
        • Dasarathy S
        • Kappus MR
        • Dunn MA
        • et al.
        Poor performance of psoas muscle index for identification of patients with higher waitlist mortality risk in cirrhosis.
        J Cachexia Sarcopenia Muscle. 2018; 9: 1053-1062
        • Chakedis J
        • Spolverato G
        • Beal EW
        • Woelfel I
        • Bagante F
        • Merath K
        • et al.
        Pre-operative Sarcopenia Identifies Patients at Risk for Poor Survival After Resection of Biliary Tract Cancers.
        J Gastrointest Surg. 2018; 22: 1697-1708
        • Kurumisawa S
        • Kawahito K.
        The psoas muscle index as a predictor of long-term survival after cardiac surgery for hemodialysis-dependent patients.
        J Artif Organs. 2019; 22: 214-221
        • Bauer J
        • Morley JE
        • Schols A
        • Ferrucci L
        • Cruz-Jentoft AJ
        • Dent E
        • et al.
        Sarcopenia: A Time for Action. An SCWD Position Paper.
        J Cachexia Sarcopenia Muscle. 2019; 10: 956-961