Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer

Wendy Demark-Wahnefried; Soroush Rais-Bahrami; Renee A. Desmond; Jennifer B. Gordetsky; Gary R. Hunter; Eddy S. Yang; Maria Azrad; Andrew D. Frugé; Yuko Tsuruta; Lyse A. Norian; Roanne Segal; William E. Grizzle

doi:10.1038/bjc.2017.303

Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer

Wendy Demark-Wahnefried, Soroush Rais-Bahrami, Renee A. Desmond, Jennifer B. Gordetsky, Gary R. Hunter, Eddy S. Yang, Maria Azrad, Andrew D. Frugé, Yuko Tsuruta, Lyse A. Norian, Roanne Segal, William E. Grizzle

Radiation Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight and obese men with prostate cancer. Methods: This single-blinded, two-arm randomised controlled trial explored outcomes of a presurgical weight loss intervention (WLI) that promoted ∼ 1 kg per week loss via caloric restriction and increased physical activity (PA). Forty overweight/obese men with clinically confirmed prostate cancer were randomised to the WLI presurgery or to a control arm; changes in weight, body composition, quality-oflife, circulating biomarkers, gene expression, and immunohistochemical markers in tumour and benign prostatic tissue were evaluated. Results: The study period averaged 50 days. Mean (s.d.) change scores for the WLI vs control arms were as follows: weight: -4.7 (3.1) kg vs -2.2 (4.4) kg (P = 0.0508); caloric intake: -500 (636) vs -159 (600) kcal per day (P = 0.0034); PA: +0.9 (3.1) vs +1.7 (4.6) MET-hours per day (NS); vitality: +5.3 (7.14) vs -1.8 (8.1) (P = 0.0491); testosterone: +55.1 (86.0) vs -48.3 (203.7) ng dl-1 ( P= 0.0418); sex hormone-binding globulin: +14.0 (14.6) vs +1.8 (7.6) nmol l-1 (P = 0.0023); and leptin: -2.16 (2.6) vs -0.03 (3.75) (P = 0.0355). Follow-up Ki67 was significantly higher in WLI vs control arms; median (interquartile range): 5.0 (2.5,10.0) vs 0.0 (0.0,2.5) (P = 0.0061) and several genes were upregulated, for example, CTSL, GSK3B, MED12, and LAMC2. Conclusions: Intentional weight loss shows mixed effects on circulating biomarkers, tumour gene expression, and proliferative markers. More study is needed before recommending weight loss, in particular rapid weight loss, among men with prostate cancer.

Original language	English
Pages (from-to)	1303-1313
Number of pages	11
Journal	British Journal of Cancer
Volume	117
Issue number	9
DOIs	https://doi.org/10.1038/bjc.2017.303
State	Published - 2017

Bibliographical note

Funding Information:
This project is funded by the National Cancer Institute (R21 CA 161263 and P30 CA13148), the National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK079626 and P30 DK56336), and the Webb Family of Birmingham, AL. We acknowledge the efforts of the following individuals who contributed their time and expertise to this investigation: Drs Jeffrey Nix, Sunil Sudarshan, and Scott Tully; Tamika Bennett; David Bryan, MA; Deborah Della Manna; Crystal Ellis, RN; Maryellen Williams; Armando Enriquez; Heather Hunter, MS; Brandon L Kane, MA; Margaret Nelson, RN; Denise Oelschager; Scott Tully, Jr; and Amaad Rana. We also are indebted to Elizabeth Platz, ScD, MPH, who reviewed our data and offered suggestions for interpretation. Finally, we are exceptionally grateful to all of the men who participated in this trial and without whom this research would not be possible.

Publisher Copyright:
© 2017 Nature Publishing Group. All rights reserved.

Keywords

Clinical trial
Diet
Immune response
Ki67
Leptin
Prostatic neoplasms
Testosterone
Weight loss

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/bjc.2017.303

Cite this

Demark-Wahnefried, W., Rais-Bahrami, S., Desmond, R. A., Gordetsky, J. B., Hunter, G. R., Yang, E. S., Azrad, M., Frugé, A. D., Tsuruta, Y., Norian, L. A., Segal, R., & Grizzle, W. E. (2017). Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer. British Journal of Cancer, 117(9), 1303-1313. https://doi.org/10.1038/bjc.2017.303

@article{dd31ae30932645b0abcefb9e45abe79b,

title = "Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer",

abstract = "Background: Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight and obese men with prostate cancer. Methods: This single-blinded, two-arm randomised controlled trial explored outcomes of a presurgical weight loss intervention (WLI) that promoted ∼ 1 kg per week loss via caloric restriction and increased physical activity (PA). Forty overweight/obese men with clinically confirmed prostate cancer were randomised to the WLI presurgery or to a control arm; changes in weight, body composition, quality-oflife, circulating biomarkers, gene expression, and immunohistochemical markers in tumour and benign prostatic tissue were evaluated. Results: The study period averaged 50 days. Mean (s.d.) change scores for the WLI vs control arms were as follows: weight: -4.7 (3.1) kg vs -2.2 (4.4) kg (P = 0.0508); caloric intake: -500 (636) vs -159 (600) kcal per day (P = 0.0034); PA: +0.9 (3.1) vs +1.7 (4.6) MET-hours per day (NS); vitality: +5.3 (7.14) vs -1.8 (8.1) (P = 0.0491); testosterone: +55.1 (86.0) vs -48.3 (203.7) ng dl-1 ( P= 0.0418); sex hormone-binding globulin: +14.0 (14.6) vs +1.8 (7.6) nmol l-1 (P = 0.0023); and leptin: -2.16 (2.6) vs -0.03 (3.75) (P = 0.0355). Follow-up Ki67 was significantly higher in WLI vs control arms; median (interquartile range): 5.0 (2.5,10.0) vs 0.0 (0.0,2.5) (P = 0.0061) and several genes were upregulated, for example, CTSL, GSK3B, MED12, and LAMC2. Conclusions: Intentional weight loss shows mixed effects on circulating biomarkers, tumour gene expression, and proliferative markers. More study is needed before recommending weight loss, in particular rapid weight loss, among men with prostate cancer.",

keywords = "Clinical trial, Diet, Immune response, Ki67, Leptin, Prostatic neoplasms, Testosterone, Weight loss",

author = "Wendy Demark-Wahnefried and Soroush Rais-Bahrami and Desmond, {Renee A.} and Gordetsky, {Jennifer B.} and Hunter, {Gary R.} and Yang, {Eddy S.} and Maria Azrad and Frug{\'e}, {Andrew D.} and Yuko Tsuruta and Norian, {Lyse A.} and Roanne Segal and Grizzle, {William E.}",

note = "Funding Information: This project is funded by the National Cancer Institute (R21 CA 161263 and P30 CA13148), the National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK079626 and P30 DK56336), and the Webb Family of Birmingham, AL. We acknowledge the efforts of the following individuals who contributed their time and expertise to this investigation: Drs Jeffrey Nix, Sunil Sudarshan, and Scott Tully; Tamika Bennett; David Bryan, MA; Deborah Della Manna; Crystal Ellis, RN; Maryellen Williams; Armando Enriquez; Heather Hunter, MS; Brandon L Kane, MA; Margaret Nelson, RN; Denise Oelschager; Scott Tully, Jr; and Amaad Rana. We also are indebted to Elizabeth Platz, ScD, MPH, who reviewed our data and offered suggestions for interpretation. Finally, we are exceptionally grateful to all of the men who participated in this trial and without whom this research would not be possible. Publisher Copyright: {\textcopyright} 2017 Nature Publishing Group. All rights reserved.",

year = "2017",

doi = "10.1038/bjc.2017.303",

language = "English",

volume = "117",

pages = "1303--1313",

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TY - JOUR

T1 - Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer

AU - Demark-Wahnefried, Wendy

AU - Rais-Bahrami, Soroush

AU - Desmond, Renee A.

AU - Gordetsky, Jennifer B.

AU - Hunter, Gary R.

AU - Yang, Eddy S.

AU - Azrad, Maria

AU - Frugé, Andrew D.

AU - Tsuruta, Yuko

AU - Norian, Lyse A.

AU - Segal, Roanne

AU - Grizzle, William E.

N1 - Funding Information: This project is funded by the National Cancer Institute (R21 CA 161263 and P30 CA13148), the National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK079626 and P30 DK56336), and the Webb Family of Birmingham, AL. We acknowledge the efforts of the following individuals who contributed their time and expertise to this investigation: Drs Jeffrey Nix, Sunil Sudarshan, and Scott Tully; Tamika Bennett; David Bryan, MA; Deborah Della Manna; Crystal Ellis, RN; Maryellen Williams; Armando Enriquez; Heather Hunter, MS; Brandon L Kane, MA; Margaret Nelson, RN; Denise Oelschager; Scott Tully, Jr; and Amaad Rana. We also are indebted to Elizabeth Platz, ScD, MPH, who reviewed our data and offered suggestions for interpretation. Finally, we are exceptionally grateful to all of the men who participated in this trial and without whom this research would not be possible. Publisher Copyright: © 2017 Nature Publishing Group. All rights reserved.

PY - 2017

Y1 - 2017

N2 - Background: Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight and obese men with prostate cancer. Methods: This single-blinded, two-arm randomised controlled trial explored outcomes of a presurgical weight loss intervention (WLI) that promoted ∼ 1 kg per week loss via caloric restriction and increased physical activity (PA). Forty overweight/obese men with clinically confirmed prostate cancer were randomised to the WLI presurgery or to a control arm; changes in weight, body composition, quality-oflife, circulating biomarkers, gene expression, and immunohistochemical markers in tumour and benign prostatic tissue were evaluated. Results: The study period averaged 50 days. Mean (s.d.) change scores for the WLI vs control arms were as follows: weight: -4.7 (3.1) kg vs -2.2 (4.4) kg (P = 0.0508); caloric intake: -500 (636) vs -159 (600) kcal per day (P = 0.0034); PA: +0.9 (3.1) vs +1.7 (4.6) MET-hours per day (NS); vitality: +5.3 (7.14) vs -1.8 (8.1) (P = 0.0491); testosterone: +55.1 (86.0) vs -48.3 (203.7) ng dl-1 ( P= 0.0418); sex hormone-binding globulin: +14.0 (14.6) vs +1.8 (7.6) nmol l-1 (P = 0.0023); and leptin: -2.16 (2.6) vs -0.03 (3.75) (P = 0.0355). Follow-up Ki67 was significantly higher in WLI vs control arms; median (interquartile range): 5.0 (2.5,10.0) vs 0.0 (0.0,2.5) (P = 0.0061) and several genes were upregulated, for example, CTSL, GSK3B, MED12, and LAMC2. Conclusions: Intentional weight loss shows mixed effects on circulating biomarkers, tumour gene expression, and proliferative markers. More study is needed before recommending weight loss, in particular rapid weight loss, among men with prostate cancer.

AB - Background: Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight and obese men with prostate cancer. Methods: This single-blinded, two-arm randomised controlled trial explored outcomes of a presurgical weight loss intervention (WLI) that promoted ∼ 1 kg per week loss via caloric restriction and increased physical activity (PA). Forty overweight/obese men with clinically confirmed prostate cancer were randomised to the WLI presurgery or to a control arm; changes in weight, body composition, quality-oflife, circulating biomarkers, gene expression, and immunohistochemical markers in tumour and benign prostatic tissue were evaluated. Results: The study period averaged 50 days. Mean (s.d.) change scores for the WLI vs control arms were as follows: weight: -4.7 (3.1) kg vs -2.2 (4.4) kg (P = 0.0508); caloric intake: -500 (636) vs -159 (600) kcal per day (P = 0.0034); PA: +0.9 (3.1) vs +1.7 (4.6) MET-hours per day (NS); vitality: +5.3 (7.14) vs -1.8 (8.1) (P = 0.0491); testosterone: +55.1 (86.0) vs -48.3 (203.7) ng dl-1 ( P= 0.0418); sex hormone-binding globulin: +14.0 (14.6) vs +1.8 (7.6) nmol l-1 (P = 0.0023); and leptin: -2.16 (2.6) vs -0.03 (3.75) (P = 0.0355). Follow-up Ki67 was significantly higher in WLI vs control arms; median (interquartile range): 5.0 (2.5,10.0) vs 0.0 (0.0,2.5) (P = 0.0061) and several genes were upregulated, for example, CTSL, GSK3B, MED12, and LAMC2. Conclusions: Intentional weight loss shows mixed effects on circulating biomarkers, tumour gene expression, and proliferative markers. More study is needed before recommending weight loss, in particular rapid weight loss, among men with prostate cancer.

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KW - Leptin

KW - Prostatic neoplasms

KW - Testosterone

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Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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