. . .

Published ahead of Print

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Resistance Exercise Dosage in Men with Prostate Cancer:
Systematic Review, Meta-analysis, and Meta-regression

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Pedro Lopez1,2, Dennis R. Taaffe1,2, Robert U. Newton1,2,3, Daniel A. Galvão1,2
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Exercise Medicine Research Institute, Edith Cowan University, Perth, Western Australia,
Australia; 2School of Medical and Health Sciences, Edith Cowan University, Perth, Western
Australia, Australia; 3School of Human Movement and Nutrition Sciences, University of
Queensland, Queensland, Australia
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Accepted for Publication: 14 August 2020
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Medicine & Science in Sports & Exercise® Published ahead of Print contains articles in unedited
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Copyright © 2020 the Author(s). Published by Wolters Kluwer Health on behalf of the
American College of Sports Medicine
Medicine & Science in Sports & Exercise, Publish Ahead of Print
DOI: 10.1249/MSS.0000000000002503

Resistance Exercise Dosage in Men with Prostate Cancer:

Systematic Review, Meta-analysis, and Meta-regression

Pedro Lopez1,2, Dennis R. Taaffe1,2, Robert U. Newton1,2,3, Daniel A. Galvão1,2

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1
Exercise Medicine Research Institute, Edith Cowan University, Perth, Western Australia,

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Australia; 2School of Medical and Health Sciences, Edith Cowan University, Perth, Western

Australia, Australia; 3School of Human Movement and Nutrition Sciences, University of

Queensland, Queensland, Australia

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Address for correspondence and reprint requests to:

Pedro Lopez, MSc

Exercise Medicine Research Institute

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Edith Cowan University

270 Joondalup Drive, Joondalup WA 6027

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AUSTRALIA

T +61 416463228
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Email: [email protected]

Acknowledgments: Pedro Lopez is supported by the National Health and Medical Research

Council (NHMRC) Centre of Research Excellence (CRE) in Prostate Cancer Survivorship

Scholarship. Daniel A. Galvão and Robert U. Newton are funded by a NHMRC CRE in Prostate
Cancer Survivorship. The results of the study are presented clearly, honestly, without fabrication,

falsification, or inappropriate data manipulation, and do not constitute endorsement by the

American College of Sports Medicine.

Conflict of Interest: None to declare.

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Role of funding source: Sponsors had no involvement in the study design, analysis or

interpretation of data, manuscript writing and decision to submit the manuscript for publication.

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This is an open-access article distributed under the terms of the Creative Commons Attribution-

Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to

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download and share the work provided it is properly cited. The work cannot be changed in any

way or used commercially without permission from the journal.

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ABSTRACT

Purpose: Resistance training (RT) improves an array of treatment-related adverse effects in men

with prostate cancer, however, the minimal dosage required is unknown. We systematically

reviewed the RT effects in prostate cancer patients to determine the minimal dosage regarding

the exercise components (type, duration, volume, and intensity) on body composition, physical

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function, muscle strength, cardiorespiratory fitness, body mass index (BMI), and prostate-

specific antigen (PSA). Methods: Using PRISMA guidelines, MEDLINE, CINAHL, EMBASE,

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SPORTDiscus, and Web of Science databases were searched. Eligible randomised controlled

trials examined prostate cancer patients undertaking resistance-based exercise programs during

or following treatment. Meta-analysis was undertaken when more than 3 studies were included.
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Associations between mean differences and the exercise components were tested by univariate

and multivariate meta-regression analysis. Results: Twenty-four papers describing 22 trials and

involving 1,888 prostate cancer patients were included. Exercise improved fat mass (-1% in body

fat and -0.5 kg in fat mass), lean mass (+0.5 kg in lean and appendicular lean mass), functional
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capacity (i.e., chair rise, 400-m test, 6-m fast walk and stair climb tests) and fitness outcomes
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(i.e., VO2 peak and muscle strength) (P=0.040 - <0.001) with no change in BMI or PSA (P= .440

- .735). Meta-regression indicated no association between exercise type, RT duration, weekly

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volume and intensity and primary outcomes (P= .075 - .965). There was a significant association

between RT intensity and chest press muscle strength (favouring moderate-intensity, P= .012),

but not in other secondary outcomes. Conclusion: In untrained older men with prostate cancer

initiating an exercise program, lower volume at moderate-to-high intensity is as effective as

higher volume RT for enhancing body composition, functional capacity and muscle strength in

the short-term.

Keywords: Prostate cancer; resistance training; dose-response effects; minimal dosage; health-

related outcomes.

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1. INTRODUCTION

The benefits of exercise medicine have been widely attested in different cancer

populations (1, 2). In prostate cancer patients, for example, resistance exercise alone, or

combined with aerobic training has been shown to reduce post-surgical impairments from

prostatectomy (3), reverse the array of adverse effects from androgen deprivation therapy (ADT)

(4-11), and preserve physical function in those with bone metastases (12), in addition to

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improvements in quality of life (5, 8, 12). However, although the role of exercise medicine is

being expanded to include low-grade cancer patients undergoing active surveillance (13-15), or

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high-grade patients in order to enhance tumour growth suppression (16) and survival (17),

information regarding the actual exercise dose-response still needs to be determined (18).
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Considering the overall exercise benefits in prostate cancer patients, the assumption that a

given exercise dosage will promote benefits in all outcomes is premature. In the most recent

exercise guideline for cancer patients (19), a specific resistance exercise dosage (e.g., 2 sets of 8-

15 reps at 60-85% of one-repetition maximum (1RM)) was recommended to address or counter

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anxiety, fatigue, and depressive symptoms based on high-quality publications. However, the
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disproportionately large number of breast cancer trials compared to other cancer trials from

which the recommendations were derived precludes more accurate recommendations for prostate
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cancer patients (19). Further, the paucity of comparative trials regarding resistance training

components (i.e., frequency, intensity, and volume) makes it difficult to establish the dose-

response effect on commonly reported outcomes. In this report, we examined the resistance

exercise dosage in body composition and functional capacity given their strong association with

risk of progression and mortality in prostate cancer patients (20-23).

 Thus, the aim of the present study is to: 1) systematically review and analyse the

resistance training effects on body composition measures, functional capacity tests,

cardiorespiratory fitness, muscle strength, body mass index (BMI), and prostate-specific antigen

(PSA) levels; and 2) verify the minimal dose regarding the prescribed exercise components (i.e.,

type, duration, volume, and intensity) and effects on these outcomes.

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2. METHODS

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2.1. Study selection procedure

The study was undertaken in accordance with the Preferred Reporting Items for

Systematic Reviews and Meta-Analyses (PRISMA) statement (24, 25), and the method used was
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based on the minimum criteria established by the Cochrane Back Review Group (CBRG) (26).

This systematic review was not registered in any prospectively systematic review database (e.g.,

PROSPERO).
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This review included published data from randomised controlled trials that evaluated the
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effects of resistance-based exercise programs in prostate cancer patients at any treatment stage

(e.g., presurgical, during treatment, and with bone metastases). The primary outcomes of this
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review were body composition (i.e., body fat percentage, fat mass, trunk fat mass, lean mass, and

appendicular lean mass), and functional capacity tests (i.e., 30s sit-to-stand-test, 6-minute walk,

400-m walk, 6-m usual and fast walk, timed up-and-go, stair climb, and repeated sit-to-stand

where patients repeated the task 5 times). The secondary outcomes were cardiorespiratory fitness

(i.e., VO2peak or VO2max), muscle strength (i.e., chest press, leg press, leg extension, and seated
row), PSA and BMI. Trials were excluded when: 1) home-based exercise was used in the whole

intervention period; 2) involved mixed cancer patients without specific information on prostate

cancer patient results; 3) did not include or report the specific outcomes included in this review,

or did not include sufficient information for analysis; and 4) written in a language other than

English. Eligibility was assessed independently evaluated in duplicate, with differences resolved

by consensus.

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The search was conducted up to November 2019 using the following electronic

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databases: MEDLINE, CINAHL, EMBASE, SPORTDiscus, and Web of Science. The terms

used were: ‘prostate cancer’ and ‘resistance training’ in association with a list of sensitive terms

to search for experimental studies. In addition, we performed a manual search of the reference
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lists provided in the selected papers as well as previous systematic reviews and meta-analytic

studies (27-33) to detect studies potentially eligible for inclusion. The search strategy used is

shown in the Supplemental Digital Content Table S1 (see in Supplemental Digital Content 1,

literature search strategy, http://links.lww.com/MSS/C125).

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2.2. Data extraction

Titles and abstracts of all articles identified by the search strategy were independently
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evaluated in duplicate. Abstracts that did not provide sufficient information regarding the

inclusion and exclusion criteria were selected for full-text evaluation. In the second phase, the

same reviewers independently evaluated these full-text articles and selected them in accordance

with the eligibility criteria. Disagreements between reviewers were resolved by consensus. The

data extraction was performed via a standardised form. Information on the interventions,
outcomes, and patients were collected. Study characteristics, intervention duration, components

of the resistance training prescription (i.e. frequency, intensity, volume, and modality),

adherence (i.e., number of patients that completed the program), attendance (i.e., number of

sessions attended), compliance (i.e., number of patients that successfully completed the exercise

prescription), and adverse events were extracted, along with the main outcomes. The prescribed

resistance training was summarised as follows: frequency (number of sessions per week),

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intensity (prescribed intensity of resistance training), type (resistance training, combined

resistance and aerobic training, or multimodal exercise program), and volume (sets and

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repetitions). When studies incorporated supervised and unsupervised periods of training,

information was extracted on the longest period of the supervised exercise intervention.

Outcomes were extracted in their absolute units (e.g., kg for lean and fat mass assessments).
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When graphs were used instead of numerical data, the graphs were measured through their plots

using a specific tool for data extraction (WebPlotDigitizer, San Francisco, California, USA) (34).

2.3. Assessment of Risk of Bias

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Risk of bias of individual studies was evaluated according to the 2nd version of the
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Cochrane risk-of-bias tool for randomised trials (RoB 2) (35), focusing on different aspects of

the trial design, conduct and reporting. Each assessment using the RoB 2 tool is focused at the
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outcome level. The six-item instrument evaluates: 1) the randomisation process; 2) deviation

from intended interventions; 3) missing outcome data; 4) measurement of the outcome; 5)

selection of the reported result; and 6) overall bias, and was used to evaluate each included

randomised controlled trial for each outcome of interest. Risk of bias for each of the six domains

was expressed as “low risk”, “some concern” and “high risk” (35).
2.4. Data analysis

The pooled-effect estimates were obtained from the mean difference of baseline to the

final assessment of the intervention for each group. These values were expressed as the mean

difference between-groups. In studies with multiple exercise interventions, the groups were

divided with each respective sample size, within-group mean difference, and SD or 95% CI for

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further analysis. Meta-analyses were conducted for overall studies and a subgroup analysis was

provided based on RoB 2.0 low risk classification when more the 3 studies were included.

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Calculations were performed using a random-effects model (36). The level of significance was

set at P ≤0.05. Statistical heterogeneity was assessed using the Cochran Q test. A threshold P-

value of 0.1 as well as values greater than 50% in the statistical test of heterogeneity (I²) were
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considered indicative of high heterogeneity (37). Heterogeneity between studies was explored by

omitting one study at a time and comparing the pooled with the original estimates, while the

presence of publication bias was explored by contour-enhanced funnel plots along with Egger’s

test, considering a P-value <0.1 as indicative of publication bias (38, 39). When necessary, the
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trim-and-fill computation was used to estimate the effect of publication bias on the interpretation
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of results (40, 41). Analyses were conducted using the package metan, confunnel, metabias, and

metatrim from Stata 14.0 software (Stata, College Station, USA). Forest plots presented for the
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outcome measures are after sensitivity analysis and/or trim-and-fill procedure adjustments.

In addition, we tested the association between the mean difference effect and the exercise

components to identify a dose-response relationship using univariate and multivariate meta-

regression. Using one variable at a time or multivariable models we assessed whether

components such as type, intervention duration, prescribed weekly volume and peak intensity

influence the association of resistance-based exercise with the main effects. Analyses were

undertaken in outcomes significantly affected by exercise provided the models had more than 5

studies. For intervention duration, prescribed weekly volume and peak intensity, analyses were

considered when the values presented a range higher than 5%, while exercise type was coded as

0= resistance training alone, and 1= resistance training combined with other components (e.g.,

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aerobic, flexibility, impact-loading, or balance). Analyses were conducted using the package

metareg from Stata 14.0 software (Stata, College Station, USA).

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3. RESULTS

3.1. Studies included

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All studies selected reported the aim to investigate the effect of resistance training (i.e.

resistance training alone, combined with aerobic exercise, or included in a multimodal exercise

program) in prostate cancer patients at any treatment stage. We retrieved 1,030 studies, 794 of

which were retained for screening after duplicate removals. Of these, 694 were excluded and 100
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full-text articles were assessed for eligibility (Figure 1). The eligibility assessment resulted in 23
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papers (describing 21 trials) (5-12, 42-56) which were included in the present review and meta-

analyses (see in Table S2, Supplemental Digital Content 2, characteristics of included studies,
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http://links.lww.com/MSS/C126), with 6 to 13 studies being included in the dose-response

relationship analysis involving exercise type, intervention duration, prescribed weekly volume

and peak intensity.

INSERT FIGURE 1 HERE

3.2. Prostate cancer patients and exercise intervention characteristics

A total of 1,748 prostate cancer patients with an average age of 69.5±2.1 yrs participated

in the included studies. Exercise interventions were predominantly undertaken in patients on

ADT (17 of 23 studies) (5, 7-9, 11, 42, 44-49, 52-56). Exercise modality included predominantly

combined resistance and aerobic training (12 of 23 studies) (5-7, 9, 10, 42, 44, 46, 51-53, 56)

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followed by multimodal exercise program (4 of 23 studies) (11, 12, 49, 55), resistance training

plus impact-loading (5 of 23 studies) (7, 9, 45, 47, 50), and resistance training only (4 of 23

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studies) (8, 43, 48, 54), in a cohort of 901 patients allocated to the intervention group compared

to 847 patients in the control group. In addition, 3 studies (42, 44, 49) also provided nutrition

advice during the intervention. Studies were designed to compare the exercise intervention vs.
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usual care control (15 of 23 studies) (5, 8, 11, 12, 42-44, 46, 48-50, 51-53, 56), a home-based

program involving aerobic or flexibility training and physical activity (6 of 23 studies) (6, 10, 45,

47, 54, 55), or to a delayed exercise group (2 of 23 studies) (7, 9). Two studies compared

multiple exercise interventions (7, 9).

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The mean exercise intervention duration was 19.5±10.7 wks with an average of 2.4±0.7

sessions per week. The average total prescribed resistance training volume was 9,136±4,534
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repetitions with a weekly training volume of 468±177 repetitions. In addition, the mean peak

intensity reached throughout the resistance training program was 79±8% of 1-RM ranging from

60 to 85%. Information about resistance training frequency was not reported by one study (54),

while 4 studies did not report volume (42, 44, 49, 55), or intensity (42, 51, 55, 56), respectively.

Exercise program adherence ranged from 74 to 100% (reported in 22 of 23 studies) (5-9, 11, 12,
42-56), while the attendance and compliance ranged from 65 to 100% (reported in 21 of 23

studies) (5-12, 42, 43, 45-47, 49-56), and from 85 to 94% (reported in 5 of 23 studies) (42, 43,

48, 50, 54), respectively. Adverse events related to the exercise interventions were identified in 8

studies (6, 8, 9, 46, 48, 51, 52, 55), while 14 studies (5, 7, 11, 12, 42-45, 47, 49, 50, 53, 54, 56)

reported no adverse events throughout the intervention period. The adverse events were mostly

related to musculoskeletal pain (e.g., back, shoulder, and knee), and only 1 study (54) presented

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a moderate adverse event with no detail provided.

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3.3. Risk of bias assessment

For the primary outcomes of this review, 13.3% of the studies presented some concern

for risk of bias in body composition assessment (2 of 15 studies) (49, 56), and 76.9% in the
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functional capacity tests (10 of 13 studies) (5, 6, 9, 12, 43, 46, 48, 51, 52, 54). The concerns in

body composition were mainly due to the measurement of the outcome as 2 studies (49, 56)

evaluated body composition outcomes through the use of bioelectrical impedance. For functional

capacity, the concerns were mainly due to the measurement of the outcome as studies performed
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non-blinded assessments on measurement of the outcome (76.9%, 10 of 13 studies) (5, 6, 9, 12,

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43, 46, 48, 51, 52, 54) and one study (7.7%, 1 of 13 studies) (51) did not report the concealment

of allocation in the randomisation process. For the secondary outcomes, concerns were observed
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in cardiorespiratory fitness (some concerns: 60.0%, 3 of 5 studies) (44, 54, 55), muscle strength

(some concerns: 84.6%, 11 of 13 studies) (5, 6, 7, 8, 10, 12, 43, 46, 48, 51, 54), and BMI (16.7%,

1 of 6 studies) (48). Concerns were not observed in the PSA assessment. The overall risk of bias

assessment is shown in Table S3 (see in Supplemental Digital Content 3, overall risk of bias of

included studies, http://links.lww.com/MSS/C127), while the individual assessment is presented

in Figure S1 (see in Supplemental Digital Content 4, individual risk of bias assessment,

http://links.lww.com/MSS/C128).

3.4. Exercise effects on body composition

Exercise resulted in significant positive overall effects in percent body fat (-1.0%, 95%

CI: -1.3 to -0.6%), fat mass (-0.6 kg, 95% CI: -0.8 to -0.3 kg), trunk fat mass (-0.3 kg, 95% CI: -

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0.6 to -0.0 kg), lean mass (0.5 kg, 95% CI: 0.3 to 0.7 kg) and appendicular lean mass (0.4 kg,

95% CI: 0.3 to 0.7 kg) with heterogeneity ranging from I2= 0 to 47% after sensitivity analysis

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and/or trim-and-fill procedure adjustments (Figure 2 and 3). The samples ranged from 490 to 917

participants (see in Table S4, Supplemental Digital Content 5, overall and subgroup analyses,

http://links.lww.com/MSS/C129). In subgroup analysis, the main effects were significantly

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maintained in the outcomes (I2= 0 to 47%; P= <.001 to .025). Outliers were identified in the

overall analysis for body fat percentage (6) and trunk fat mass (53), and subgroup analysis of

appendicular lean mass (7), while publication bias and trim and fill procedure suggested that data

from 3 studies were missing for appendicular lean mass (P= .050). These studies were omitted
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from the abovementioned overall and subgroup effects (Figure 2 and 3). The meta-analysis

power to detect changes in body composition was 1-β= 1.0.

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INSERT FIGURE 2 HERE

In the dose-response analysis, the univariate (P= .075 to .965; see in Table S5,

Supplemental Digital Content 6, univariate meta-regression results,

http://links.lww.com/MSS/C130) and multivariate meta-regression models (P= .203 to .785; see

in Table S6, Supplemental Digital Content 7, multivariate meta-regression results,

http://links.lww.com/MSS/C131) did not explain the variation in body composition outcomes.

INSERT FIGURE 3 HERE

3.5. Exercise effects on functional capacity

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There was a significant positive overall exercise effect for the time to perform the 30s sit-

to-stand repetitions (2.8 reps, 95% CI: 1.7 to 4.0 reps), repeated sit-to-stand test (-1.0 sec, 95%

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CI: -1.4 to -0.6 sec), 400-m walk (-8.3 sec, 95% CI: -12.4 to -4.2 sec), 6-m fast walk (-0.1 sec,

95% CI: -0.2 to -0.0) and stair climb (-0.2 sec, 95% CI: -0.3 to -0.1 sec) with an heterogeneity

ranging from I2=0 to 45.2% after sensitivity analysis and/or trim-and-fill procedure adjustments
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(Figure 4). The samples ranged from 213 to 519 participants (see in Table S4, Supplemental

Digital Content 5, overall and subgroup analyses, http://links.lww.com/MSS/C129). Subgroup

analyses were not undertaken on these outcomes as well as the overall analyses in the 6-min

walk test and 6-m backwards walk test given the small number of studies included (<3). The
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study of Galvão et al. (12) was considered an outlier in the 6-m fast walk time analysis and
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omitted from the abovementioned results, while publication bias was only found for the 400-m

walk (P=.063) with no trimming needed to be performed (data unchanged). The meta-analysis
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power to detect change in the 6-m usual walk and timed-up and go test was 1-β= 0.57 and 0.64,

respectively, while a 1-β= 1.0 was found for the remaining functional capacity outcomes.

INSERT FIGURE 4 HERE

 In the dose-response analysis, the univariate (P= .182 to .341; see in Table S5,

Supplemental Digital Content 6, univariate meta-regression results,

http://links.lww.com/MSS/C130) and multivariate meta-regression models (P=.358; see in Table

S6, Supplemental Digital Content 7, multivariate meta-regression results,

http://links.lww.com/MSS/C131) were not statistically significant in explaining the variation in

400-m test performance. Analyses of 30s sit-to-stand, 6-min walk test, 6-m usual and fast walk,

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stair climb, and repeated sit-to-stand tests were not undertaken due to the small number of

studies (≤5) reporting on these components. Performing univariate meta-regression resulted in

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non-significant associations between exercise type, resistance training duration, weekly volume

and peak intensity with 30s sit-to-stand (P= .311 for exercise type and resistance training

duration), 6-minute fast walk (P= .165 - .793), stair climbs (P= .523 – .930) and repeated sit-to-
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stand tests (P= .681 - .868).

3.6. Exercise effects on secondary outcomes

There was a significant increase in chest press (3.9 kg, 95% CI: 2.9 to 4.9 kg), leg press
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(23.5 kg, 95% CI: 15.2 to 31.7 kg), leg extension (8.8 kg, 95% CI: 6.9 to 10.7 kg) and seated row

strength (5.2 kg, 95% CI: 3.9 to 6.5 kg) with heterogeneity ranging from I2= 0 to 77.4% after
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sensitivity analysis and/or trim-and-fill procedure adjustments (Figure 5). The samples ranged
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from 321 to 728 participants (see in Table S4, Supplemental Digital Content 5, overall and

subgroup analyses, http://links.lww.com/MSS/C129). Subgroup analyses were not undertaken

for these outcomes due to the small number of studies that were considered of low risk (<3).

Outliers were identified in the overall analysis for chest press (8), leg extension (12) and seated

row test (54). Meta-analysis power to detect change in muscle strength was 1-β= 1.0.
INSERT FIGURE 5 HERE

Regarding VO2peak, there was a positive overall effect of 1.3 ml.kg.min-1 (95% CI: 0.8 to

1.7 ml.kg.min-1) after the publication bias and trim and fill procedure suggesting that data were

missing from 2 studies (P= .078; see in Table S4, Supplemental Digital Content 5, overall and

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subgroup analyses, http://links.lww.com/MSS/C129, and Figure 6). Finally, exercise did not

result in a significant change in BMI or PSA levels (P= .440 - .735; see in Table S4,

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Supplemental Digital Content 5, overall and subgroup analyses,

http://links.lww.com/MSS/C129, and Figure 6). Meta-analysis power to detect change in VO2peak

was 1-β= 1.0, while power for BMI and PSA was 0.25 and 0.57, respectively.
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INSERT FIGURE 6 HERE

In the univariate dose-response analysis, resistance training type and intensity (r2= 64.0%,
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P= .010; and r2= 100%, P< .001, respectively; see in Table S5, Supplemental Digital Content 6,
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univariate meta-regression results, http://links.lww.com/MSS/C130) explained the variation in

chest press muscle strength. In the multivariate model, gain in chest press muscle strength (r2=
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100%, P= .012, see in Table S6, Supplemental Digital Content 7, multivariate meta-regression

results, http://links.lww.com/MSS/C131) was greater in studies prescribing resistance training

with moderate intensity (P= .022). Although the resistance training volume was significant in the

univariate model to explain leg extension and leg press muscle strength (P= .043 and .050,

respectively; see in Table S5, Supplemental Digital Content 6, univariate meta-regression results,
http://links.lww.com/MSS/C130), the results were not maintained in the multivariate meta-

regression model (P= .147 - .204). Dose-response analyses of VO2peak and the seated row test

were not undertaken due to the small number of studies (≤5) reporting on these components.

Performing univariate meta-regression resulted in non-significant associations between exercise

type, resistance training duration, weekly volume and peak intensity with VO 2peak (P= .598 -

.651, see in Table S5, Supplemental Digital Content 6, univariate meta-regression results,

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http://links.lww.com/MSS/C130), while seated row test variation was explained by exercise type

(coefficient ± SE: -14.9±2.9, P= .014; favouring resistance training alone), resistance training

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weekly volume (coefficient ± SE: 0.0±0.1, P= .032; favouring higher weekly volume), but not

resistance training duration (P= .624; see in Table S5, Supplemental Digital Content 6, univariate

meta-regression results, http://links.lww.com/MSS/C130).

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4. DISCUSSION

The present review produced four important findings in prostate cancer patients. First,

body composition is enhanced by resistance exercise (i.e., increase in whole body and regional
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lean mass and decrease in fat mass) regardless of type, duration, weekly volume and peak
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intensity. Second, exercise promotes significant improvements in multiple components of

physical function, in a non-linear dose-response fashion. Third, muscle strength and

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cardiorespiratory fitness are improved with exercise, with greater effects in chest press strength

resulting from resistance training performed at a moderate intensity. Finally, resistance-based

exercise does not modify BMI or affect PSA levels. Therefore, the resistance training

prescription combined with different exercise components is a potent therapy against an array of
treatment-related adverse effects in prostate cancer patients regardless of the weekly volume

prescribed when moderate-to-high intensity is achieved.

Obesity has been associated with an increased risk of biochemical recurrence and

mortality in prostate cancer patients in a dose-response fashion (20). In the meta-analysis by Cao

& Ma (20), a 5 kg.m-2 increase in BMI was associated with a 21% increased risk for biochemical

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recurrence and a 20% increased risk for prostate cancer specific-mortality. In our study, PSA

levels did not change in response to exercise involving resistance training indicating no impact of

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this exercise mode on disease progression (e.g., albeit not expected to change as most studies

were short in duration with the majority of patients having local disease). In addition, few studies

reported adverse events, and these were generally minor in nature. Moreover, the similar
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magnitude of change observed in lean mass and fat mass (i.e., increase in lean mass and decrease

in fat mass) accounts for the maintenance in BMI and may result in metabolic health benefits and

enhanced survival (57, 58). Furthermore, the lack of relationship between resistance training

weekly volume, intensity and duration indicates the potential benefit of low dosage resistance
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training to improve overall body composition. Likewise, in a previous report by Stamatakis et al.
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(59), a low weekly dosage of resistance training was associated with a ~25% reduced risk of

mortality. Thus, undertaking exercise programs that include resistance training results not only in
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benefits for body composition in men with prostate cancer, but may also provide a protective

effect against cancer recurrence and cancer-specific mortality even when performed at a low

weekly dosage. These results are of importance for prostate cancer patients and the prescription

of exercise for this patient group as it suggests that even modest amounts of exercise may result
in the accrual of significant body composition benefits and this may also contribute to increased

attendance and compliance to an exercise program.

Considering the World Health Organization (WHO) report (60), the concept of healthy

ageing should be seen as the process of developing and maintaining functional capacity. Several

studies report the association between muscle strength, cardiorespiratory fitness and functional

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tests with independence, hospitalization rate, and mortality (61-66). Thus, the observed gains in

muscle strength and cardiorespiratory fitness, and functional capacity support translation of

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exercise medicine effects into functional independence and autonomy in older prostate cancer

patients. For example, the reduction in time to walk 400-m represents an increase in the safety

margin before the threshold for disability and may help to reduce the risk for complications such
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as risk for falls and fractures (67, 68), and mortality (21). Reduced risk of mortality is also

associated with enhanced repeated sit-to-stand and stair climb test performance (22, 23). In this

way, the progression of moderate-to-high intensity in resistance training combined with other

exercise components appears to be sufficient to achieve significant improvements in functional

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capacity of patients with prostate cancer regardless of the number of weekly repetitions. Thus,
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the present findings provide an appropriate approach for prostate cancer patients as it allows a

conservative exercise prescription commencement (e.g., less repetitions per exercise at

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moderate-to-high loads) and gradual progression according to comorbidities and the patient’s

treatment-related side effects (69). Furthermore, following the non-significant relationship

between intervention duration and study outcomes, it is also possible to maintain a low dosage

resistance training program for longer periods which may help patients to keep active during and

following treatment.
 One of the critical considerations in the design of exercise trials and of its potential and

feasibility in cancer patients is related to the exercise dose-response (18, 19, 69). However, to

date the assessment and quantification of exercise dosage, as well as the lack of reporting

preclude a minimal dosage prescription for prostate cancer patients. The present review and

analysis provide information that less repetitions per exercise at moderate-to-high intensity (i.e.,

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60-85% of 1-RM) could be sufficient to achieve significant benefits for prostate cancer patients,

at least in the short-term. We hypothesize that due to the large window for adaptation in these

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undeveloped qualities, these men adapt at a similar rate within the volumes and intensities of the

studies analysed, at least over the relatively short duration of these interventions. Our results

partially agree with previous studies comparing different resistance training dosages in older
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adults (70-72), with similar results for various dosages following 12 weeks training (70, 72) but

not for longer training periods such as 20 weeks (71, 72). This could be due to the lower

threshold for muscular adaptations in untrained older participants in the initial stages of training,

and the need for a greater stimulus following this initial period. However, the lack of influence of
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intervention duration suggests the potential use of low-volume resistance training during longer
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periods in prostate cancer patients, different than that observed in healthy older adults (71, 72).

Future studies will be necessary to elucidate if higher dosage and longer duration accrues greater
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benefits in prostate cancer patients. Furthermore, considering the meta-analytic adjustments and

heterogeneity, the positive exercise results observed in body composition and multiple

components of physical function are likely to be observed across different treatment phases (e.g.,

during ADT or after primary treatment). Given the lower between-studies heterogeneity in the

meta-analysis (I2< 30%), the observed results in body fat, muscle mass, 6-minute walk, 400-m
walk, stair climb, repeated sit-to-stand and cardiorespiratory fitness indicate that prostate cancer

patients may experience similar benefits in these outcomes regardless of the treatment phase.

Thus, the low resistance training dosage could be a useful strategy to improve body composition

and muscle function in patients at different treatment stages.

The strengths of this review and analysis is that it included a large number of exercise

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trials encompassing prostate cancer patients at different disease stages (21 trials reported in 23

papers with 1,748 patients included) in a conservative approach employing univariate and

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multivariate meta-regression models, as well as sensitivity analysis to explore the common

objectively assessed physical health-related outcomes. However, there are also some limitations

that are worthy of comment. First, although our findings indicate a minimal dosage for health-
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related outcomes based on studies undertaken to date, it should not be seen as an “optimal”

dosage for each of the outcomes investigated. Second, the use of prescribed dosage (not the

actual dosage undertaken) may be considered a limitation in the present study. Although the

compliance ranges from 65 to 94% in the included studies (42, 43, 48, 50, 54), most did not
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report this metric, precluding a determination of how much exercise was actually undertaken in
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the attended sessions. We recently reported on compliance in an exercise trial on men with

prostate cancer who had bone metastases (73) and outlined the methodology and metrics that can
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be employed in future studies. Finally, the exercise program duration was considered short in

most of the included studies. Only two papers from the same trial (45, 47) lasted longer than 6

months and, as a result, it is difficult to infer our results regarding exercise dosage beyond a

period of 24 weeks in duration. Future trials involving longer exercise durations will be

necessary to confirm these results.

 In conclusion, the results indicate that there is no difference in effect when prescribing

low and high volume or moderate and high intensity resistance exercise in untrained older men

with prostate cancer on body composition, functional capacity and muscle strength outcomes, at

least in the short-term. Considering the array of benefits observed in the present study, a low

resistance training weekly volume could represent a time-efficient approach during and after

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active treatment, resulting in higher adherence, attendance and compliance while accruing

similar health and function benefits to that of higher volume exercise. We suggest the

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examination of resistance training dose-response in future trials to determine if a minimal dose-

approach could culminate in substantial cancer-related benefits.

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Acknowledgments: Pedro Lopez is supported by the National Health and Medical Research

Council (NHMRC) Centre of Research Excellence (CRE) in Prostate Cancer Survivorship

Scholarship. Daniel A. Galvão and Robert U. Newton are funded by a NHMRC CRE in Prostate

Cancer Survivorship. The results of the study are presented clearly, honestly, without fabrication,

falsification, or inappropriate data manipulation, and do not constitute endorsement by the

American College of Sports Medicine.

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Conflict of Interest: None to declare.

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Role of funding source: Sponsors had no involvement in the study design, analysis or

interpretation of data, manuscript writing and decision to submit the manuscript for publication.
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Contributorship: Substantial contributions to the conception and design of the work were done

by Pedro Lopez; Dennis R. Taaffe, Robert U. Newton, and Daniel A. Galvão. The work draft and

revision, as well as the approval of the final version, were done by Pedro Lopez; Dennis R.
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Taaffe, Robert U. Newton, and Daniel A. Galvão. In addition, all aspects of this work related to
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the accuracy or integrity were ensured by Pedro Lopez; Dennis R. Taaffe, Robert U. Newton,

and Daniel A. Galvão.

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Figure Legends/Captions:

Figure 1. Flow chart of study selection process. *, Primary outcome.

Figure 2. Mean difference effects of resistance-based exercise compared with control on

percentage body fat (A), fat mass (B) and trunk fat mass (C). Overall and subgroup analyses

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conducted with a random effects model. Grey and white circles represent study specific estimates

based on risk of bias assessment (Low risk, and some concern or high risk of bias, respectively);

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I2 represents the heterogeneity test; diamonds represent pooled estimates of random-effect meta-

analysis. *, Combined resistance and aerobic group; #, Resistance training plus impact-loading

group.
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Figure 3. Mean difference effects of resistance-based exercise compared with control on lean

mass (A) and appendicular lean mass (B). Overall and subgroup analyses conducted with a

random effects model. Grey and white circles represent study specific estimates based on risk of
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bias assessment (Low risk, and some concern or high risk of bias, respectively); I2 represents the
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heterogeneity test; diamonds represent pooled estimates of random-effect meta-analysis. *,

Combined resistance and aerobic group; #, Resistance training plus impact-loading group.
A

Figure 4. Mean difference effects of resistance-based exercise compared with control on 30s sit-

to-stand repetitions (A), 5 sit-to-stand test (B), 400-m walk test (C), 6-m usual walk test (D), 6-m

fast walk test (E), timed-up and go test (F) and stair climb test (G). Overall and subgroup

analyses conducted with a random effects model. Grey and white circles represent study specific
estimates based on risk of bias assessment (Low risk, and some concern or high risk of bias,

respectively); I2 represents the heterogeneity test; diamonds represent pooled estimates of

random-effect meta-analysis. *, combined resistance and aerobic group; #, resistance training

plus impact-loading group; 30SS, 30s sit-to-stand test; TUG, timed-up and go test.

Figure 5. Mean difference effects of resistance-based exercise compared with control on chest

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press (A), leg press (B), leg extension (C) and seated row (D). Overall and subgroup analyses

conducted with a random effects model. Grey and white circles represent study specific estimates

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based on risk of bias assessment (Low risk, and some concern or high risk of bias, respectively);

I2 represents the heterogeneity test; diamonds represent pooled estimates of random-effect meta-

analysis. *, combined resistance and aerobic group; #, resistance training plus impact-loading
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group.

Figure 6. Mean difference effects of resistance-based exercise compared with control on

VO2peak (A), body mass index (B) and prostate-specific antigen levels (C). Overall and
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subgroup analyses conducted with a random effects model. Grey and white circles represent
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study specific estimates based on risk of bias assessment (Low risk, and some concern or high

risk of bias, respectively); I2 represents the heterogeneity test; diamonds represent pooled
A

estimates of random-effect meta-analysis. BMI, body mass index; PSA, prostate-specific antigen.
Supplemental Digital Content (SDC)

SDC1.docx - (SDC 1) Table S1. Literature search strategy used for the PubMed database.

SDC2.docx - (SDC 2) Table S2. Study characteristics: treatment stage, sample size, exercise

prescription, adherence, attendance, compliance and outcomes assessed.

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SDC3.docx - (SDC 3) Table S3. Risk of bias of included studies.

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SDC4.docx - (SDC 4) Figure S1. Individual risk of bias assessment at outcome level for A)

body composition, B) functional capacity, C) cardiorespiratory fitness, D) muscle strength, E)

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prostate-specific antigen and F) body mass index. Green circles, low risk; yellow circles, some

concerns; red circles, high risk of bias.

SDC5.docx - (SDC 5) Table S4. Overall and subgroup analysis effects on body composition,
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functional capacity, and the secondary outcomes in prostate cancer patients.

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SDC6.docx - (SDC 6) Table S5. Univariate meta-regression on main outcomes mean difference
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and exercise type, resistance training duration, weekly volume and peak intensity.

SDC7.docx - (SDC 7) Table S6. Multivariate meta-regression on main outcomes mean

difference and exercise type, resistance training duration, weekly volume and peak intensity.
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(SDC 1) Table S1. Literature search strategy used for the PubMed database

#1” Search “prostate cancer”(Mesh) OR Prostate Neoplasms (title/abstract) OR Neoplasms,

Prostate (title/abstract) OR Neoplasm, Prostate (title/abstract) OR Prostate Neoplasm
(title/abstract) OR Neoplasms, Prostatic (title/abstract) OR Neoplasm, Prostatic
(title/abstract) OR Prostatic Neoplasm (title/abstract) OR Prostate Cancer (title/abstract) OR
Cancer, Prostate (title/abstract) OR Cancers, Prostate (title/abstract) OR Prostate Cancers
(title/abstract) OR Cancer of the Prostate (title/abstract) OR Prostatic Cancer (title/abstract)

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OR Cancer, Prostatic (title/abstract) OR Cancers, Prostatic (title/abstract) OR Prostatic
Cancers (title/abstract) OR Cancer of Prostate (title/abstract)

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#2” Search “resistance training”(Mesh) OR Training, Resistance (title/abstract) OR
Strength Training (title/abstract) OR Training, Strength (title/abstract) OR Weight-Lifting
Strengthening Program (title/abstract) OR Strengthening Program, Weight-Lifting
(title/abstract) OR Strengthening Programs, Weight-Lifting (title/abstract) OR Weight
Lifting Strengthening Program (title/abstract) OR Weight-Lifting Strengthening Programs
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(title/abstract) OR Weight-Lifting Exercise Program (title/abstract) OR Exercise Program,
Weight-Lifting (title/abstract) OR Exercise Programs, Weight-Lifting (title/abstract) OR
Weight Lifting Exercise Program (title/abstract) OR Weight-Lifting Exercise Programs
(title/abstract) OR Weight-Bearing Strengthening Program (title/abstract) OR Strengthening
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Program, Weight-Bearing (title/abstract) OR Strengthening Programs, Weight-Bearing

(title/abstract) OR Weight Bearing Strengthening Program (title/abstract) OR Weight-
Bearing Strengthening Programs (title/abstract) OR Weight-Bearing Exercise Program
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(title/abstract) OR Exercise Program, Weight-Bearing (title/abstract) OR Exercise

Programs, Weight-Bearing (title/abstract) OR Weight Bearing Exercise Program
(title/abstract) OR Weight-Bearing Exercise Programs (title/abstract).
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#1 AND #2
(SDC 2) Table S2. Study characteristics: treatment stage, sample size, exercise prescription, adherence, attendance, compliance and outcomes assessed.

Adherence
Exercise prescription and
Author, year Disease stage Treatment stage Experimental design Attendance Adverse events Outcomes

D
sample
Compliance
In the resistance Body fat;
Resistance training
training group, Cardiorespiratory
I-IV; Radiotherapy; n=40, 3 sessions per Adh: 82.5%

TE
Segal et al., 121 randomised one man fitness;
Gleason Score: Radiotherapy week for 24 weeks Att: 88.0%
2009(8) RT vs. AT vs. UC experienced chest Chest press and leg
6.7±0.9 plus ADT performing 2 sets of 8-12 Comp: NR
pain during press 1-RM;
reps at 60-70% of 1-RM
exercise. PSA
Body fat, Fat mass,
Trunk fat mass,
Lean mass,

EP
Appendicular lean
Combined resistance mass;
Localised and and aerobic training 400-m walk, 6-m
57 randomised
nodal n=29, 2 sessions per Adh: 96.6% usual, fast and
Galvão et al., Combined resistance No adverse
metastases; ADT week for 12 weeks; Att: 94.0% backwards walk,
2010(5) and aerobic training events.
Gleason Score: RT: 2-4 sets of 6-12RM Comp: NR stair climb,
vs. UC
7.3 AT: 15-20min at 65-80% repeated sit-to-

C HR stand;
Chest press, leg
press and seated
row 1-RM;
C
PSA
50 randomised Combined resistance
Adh: 84.0% 30s sit-to-stand
Bourke et al., Gleason Score: Lifestyle intervention and aerobic training No adverse
ADT Att: 95.2% repetitions;
2011(42) 7±1.1 (combined resistance n=25, 2 sessions per events.
A
Comp: 87.0% BMI
and aerobic training, week for 12 weeks;
 nutrition advice, and AT: 30min at 55-85%
home-based AT) vs. HR;
UC RT: 2-4 sets
Body fat, Fat mass,

D
Trunk fat mass,
Lean mass,
Resistance training Appendicular lean
20 randomised n=10, 2 sessions per Adh: 80.0% mass;
Cormie et al., Gleason Score: No adverse

TE
Bone metastasis RT plus home-based week for 12 weeks Att: 83.0% 400-m walk, 6-m
2013(43) 8.2 events.
AT vs. UC performing 2-4 sets of 8- Comp: 93.2% usual and fast
12RM walk, Timed up-
and-go;
leg extension 1-
RM
Body fat, Fat mass,

EP
One participant
Lean mass,
Combined resistance with pre-existing
100 randomised Appendicular lean
and aerobic training back pain elected
Combined resistance mass;
Galvão et al., n=50, 2 sessions per Adh: 84.0% to cease the
Previous ADT and aerobic training 400-m walk,
2014(6) II-IV week for 24 weeks Att: 77.0% exercise program,
and radiotherapy plus home-based AT repeated sit-to-
(RADAR trial) RT: 2-4 sets of 6-12RM Comp: NR as did one patient
vs. physical activity stand;
AT: 20-30min at 70-85% with a pre-
material Chest press and leg

C 100 randomised
Lifestyle intervention
HR

Combined resistance
and aerobic training
existing knee
injury.
extension 1-RM;
PSA
C
(combined resistance n=50, 2 sessions per Adh: 94.0%
Bourke et al., No adverse BMI;
NR ADT and aerobic training, week during 12 weeks; Att: 94.0%
2014(44) events. PSA
nutrition advice, and AT: 30min at 55-75% of Comp: NR
A
home-based AT) HR;
vs. UC RT: 2-4 sets of 8-12 reps
 at 60% of 1-RM
Impact + Resistance
training
51 randomised
ADT; n=29, 2 sessions per Repeated sit-to-
Impact + RT plus Adh: 82.8%

D
Winters-Stone Chemotherapy; week for 48 weeks; No adverse stand;
NR home-based AT vs. Att: 83.0%
et al., 2015(45) Radiotherapy; Impact: 50 two-footed events. Chest press and leg
home-based AT and Comp: NR
Bone metastasis jumps from the ground press 1-RM
FLX
with weighted vests

TE
RT: 1-3 sets of 8-12RM
Body fat, Fat mass,
Trunk fat mass,
Lean mass,
Appendicular lean
One participant
mass;
from the exercise
Combined resistance 400-m walk, 6-m

EP
group withdrew
63 randomised and aerobic training usual, fast and
from the
ADT; Combined resistance n=32, 2 sessions per Adh: 93.8% backwards walk,
Cormie et al., Gleason Score: intervention due
Chemotherapy; and aerobic training week for 12 weeks; Att: 96.2% stair climb,
2015(46) 7.5 to feeling too
Radiotherapy plus home-based AT AT: 20-30min at 70-85% Comp: NR repeated sit-to-
nauseous, dizzy
vs. UC HR; stand;
and fatigued to
RT: 1-4 sets of 6-12RM Cardiorespiratory
attend the exercise
fitness;

C sessions.
chest press, leg
press and seated
row 1-RM;
PSA
C
51 randomised Impact + Resistance
ADT; Impact + RT plus training Adh: 82.8% Body fat, Fat mass,
Winters-Stone Including bone No adverse
Chemotherapy; home-based AT vs. n=29, 2 sessions per Att: 84.0% Trunk fat mass,
et al., 2015(47) metastases events.
A
Radiotherapy home-based AT and week for 48 weeks; Comp: NR Lean mass
FLX Impact: 50 two-footed
 jumps from the ground
with weighted vests
RT: 1-3 sets of 8-12RM
Body fat, Fat mass,
Resistance training Three patients in

D
Trunk fat mass,
n=28, 3 sessions per the resistance
Lean mass,
week for 16 weeks training group
Intermediate and Appendicular lean
Radiotherapy performing 1-3 sets of Adh: 78.6% discontinued the
Nilsen et al., high-risk based 58 randomised mass;
plus ADT; 10RM on Mondays, 2-3 Att: NR intervention due

TE
2015(48) on PSA and RT vs. UC 30s sit-to-stand-
following ADT sets of 10 reps at 80-90% Comp: 85.0% to pain, two due
primary tumour test, stair climb;
of 10RM on to pain in the knee
Chest press and leg
Wednesdays, and 2-3 and one patient
press 1-RM;
sets of 6RM on Fridays. due to back pain.
BMI
Multimodal exercise
program

EP
50 randomised n=25, 2 sessions per
Fat mass, Lean
Multimodal exercise week for 12 weeks; Adh: 80.0%
Gilbert et al., No adverse mass
NR ADT program plus home- AT: 30min at 55-75% Att: 93.0%
2016(49) events. BMI;
based AT and RT vs. HR Comp: NR
PSA
UC RT: 2-4 sets of 8-12 reps
at 60% of 1-RM
BAL: NR

C
Patients
following
primary
treatment other
64 randomised
Impact + RT vs. UC
Impact + Resistance
training
n=32, 2 sessions per
Adh: 100%
Body fat, Fat mass,
Trunk fat mass,
Lean mass;
C
Winters-Stone week for 24 weeks; No adverse
NR than hormone Sessions with patients Att: 78.0% repeated sit-to-
et al., 2016(50) Impact: 1 set of 8–15 events.
therapy and not and spouses training Comp: 94.0% stand;
repetitions with weighted
currently together Chest press and leg
vests
A
undergoing press 1-RM
RT: 1 set of 8-15RM
radiation or
 chemotherapy
One man in the
intervention
Surgery; condition

D
Radiotherapy; Combined resistance aggravated a
30s sit-to-stand-
Surgery plus 119 randomised and aerobic training previous rotator
test, 6-minute
radiotherapy; Combined resistance n=53, 2 sessions per Adh: 98.1% cuff injury during
Gaskin et al., walk;
I-III ADT plus and aerobic training week for 12 weeks; Att: 75.0% exercise training.
2016(51) BMI;

TE
radiotherapy; plus home-based AT AT: 20-30min at 40-70% Comp: NR One man in the
Chest press and leg
Surgery plus and RT vs. UC HR control condition
press 1-RM
radiotherapy and RT: 2 sets of 8-12 reps aggravated a
ADT. previous meniscus
injury during
baseline testing.
Combined resistance

EP
and aerobic training Three overuse
72 randomised n=36, 3 sessions per injuries to the
Adh: 97.2%
Hojan et al., Gleason Score: Combined resistance week for 12 weeks; lower extremities 6-minute walk;
ADT Att: 86.0%
2017(52) 8.8±1.9 and aerobic training AT: 30min at 70-80% were reported in BMI
Comp: NR
vs. UC HR the exercise
RT: 2 sets of 8 reps at group.
70-75% of 1-RM

Taaffe et al.,
Localised and
nodal
C
ADT;
ADT plus
radiotherapy;
159 randomised
Impact + RT vs.
Impact + Resistance
training
n=57, 2 sessions per
week for 24 weeks;
Adh: 74.1% &
87.0%
Two men in
Impact + RT
group withdrew
due to compressed
C
Combined resistance
2017(9) metastases; ADT plus Impact: bounding, Att: 65.0 and spinal discs and 400-m walk
and aerobic training
(NHMRC trial) Gleason Score: antiandrogen; skipping, drop jumping, 69.0% shoulder issues.
plus home-based AT
7.8 ADT plus hopping, and leaping Comp: NR Two men in
vs. Delayed AT
A
surgery activities Combined RT and
RT: 2-4 sets of 6-12RM AT had
 Combined resistance cardiovascular
and aerobic training problems, with
n=54, 2 sessions per one requiring
week for 24 weeks; heart bypass

D
AT: 20-30min at 60-85% surgery while
HR another
RT: 2-4 sets of 6-12RM participant
developed back

TE
pain.
Combined resistance
Body fat, Fat mass,
ADT; 97 randomised and aerobic training
Trunk fat mass,
ADT plus Combined resistance n=50, 2 sessions per Adh: 86.0%
Wall et al., Gleason Score: No adverse Lean mass;
radiotherapy; and aerobic training week for 24 weeks; Att: 69.0%
2017(53) 8.0 events. Cardiorespiratory
ADT plus plus home-based AT RT: 2-4 sets of 6-12RM Comp: NR
fitness;
antiandrogen vs. UC AT: 20-30min at 70-90%

EP
PSA
HR
Combined resistance
57 randomised
and aerobic training
Combined resistance
Taaffe et al., n=28, 2 sessions per Adh: NR
Previous ADT and aerobic training
2018(10) II-IV week during 24 weeks; Att: 77.0% NR Leg press 1-RM
and radiotherapy plus home-based AT
(RADAR trial) RT: 2-4 sets of 6-12RM Comp: NR
vs. physical activity
AT: 20-30min at 70-85%

Patients with
C
ADT;
material
HR
Multimodal exercise
program
n=28, 3 sessions per
Fat mass and Lean
mass;
400-m walk, 6-m
C
Prostatectomy; 57 randomised Adh: 82.1%
Galvão et al., established bone week for 12 weeks; No adverse usual, fast and
Radiotherapy; Multimodal exercise Att: 89.0%
2018(12) metastatic RT: 2 sets of 10-12 reps events. backward walk,
Brachytherapy; program vs. UC Comp: NR
disease at 10-12RM Timed up-and-go,
Chemotherapy
A
AT: 20-30min at 60-85% repeated sit-to-
HR stand;
 FLX: 2-4 reps for 30-60 Leg extension 1-
seconds RM
Body fat, Fat mass,
Lean mass,

D
Appendicular lean
ADT; 37 randomised
Including bone Resistance training mass;
Antiandrogen; RT vs. home-based
and nodal n=16, 3 sessions per Adh: 87.5% 400-m walk, timed
Dawson et al., Radiotherapy; FLX No adverse
metastases week for 12 weeks Att: 93.8% up-and-go, stair
2018(54) Surgery; Part of the sample events.

TE
Gleason Score: performing 3 sets of 8-15 Comp: 88.3% climb;
Chemotherapy received whey protein
7.5 reps at 60-83% of 1-RM Chest press, leg
isolate (~50%)
extension, leg
press and seated
row 1-RM
Three adverse
events (two grade

EP
2 events in home-
based exercise
53 randomised
Multimodal exercise program
Gleason score Personal supervised Adh: 85.0%
Alibhai et al., program participants and Cardiorespiratory
range from 6 to ADT vs. group supervised Att: 75.0%
2019(55) n=19, 3 sessions per one grade 1 event fitness
10 vs. home-based Comp: NR
week for 24 weeks in a personal
exercise program
supervised

Locally
C Combined resistance
participant;
primarily
musculoskeletal)
C
50 randomised
advanced and and aerobic training Fat mass;
ADT; Combined resistance Adh: 91.7%
Ndjavera et al., metastatic n=24, 2 sessions per No adverse Cardiorespiratory
ADT plus and aerobic training Att: 70.0%
2019(56) patients; week during 12 weeks; events. fitness;
radiotherapy plus home-based AT Comp: NR
A
Gleason score AT: 6 bouts of 5 min at PSA
and RT vs. UC
range from 6 to 55-85% HR
 10 RT: 2-4 sets of 10 reps at
11-15 RPE
104 randomised Multimodal exercise
Combined resistance program

D
and aerobic training + n=54, 3 sessions per
ADT; Impact loading plus week for 24 weeks; Body fat, Fat mass,
ADT plus home-based AT vs. Impact: bounding, Adh: 88.9% Trunk fat mass,
Taaffe et al., Gleason score: No adverse
surgery; UC skipping, drop jumping, Att: 79.0% Lean mass,
2019(11) 7.6 events.

TE
ADT plus All patients received hopping, and leaping Comp: NR Appendicular lean
radiotherapy standard daily activities mass
supplementation with RT: 2-4 sets of 6-12RM
calcium and vitamin AT: 25-40min at 60-85%
D3 HR
Impact + Resistance
training

EP
n=57, 2 sessions per
week for 24 weeks;
Impact: bounding, Fat mass, Lean
154 randomised
skipping, drop jumping, mass,
Localised and ADT; Impact + Resistance Adh: 73.7% &
hopping, and leaping Appendicular lean
Newton et al., nodal ADT plus training vs. Combined 86.0%
activities No adverse mass;
2019(7) metastases; radiotherapy; resistance and aerobic Att: 65.0 and
RT: 2-4 sets of 6-12RM events. Chest press, leg
(NHMRC trial) Gleason Score:
7.8
C
ADT plus
antiandrogen.
training plus home-
based AT vs. Delayed
AT
Combined resistance
and aerobic training
n=50, 2 sessions per
week for 24 weeks;
70.0%
Comp: NR
press, leg
extension and
seated row 1-RM
C
AT: 20-30min at 60-85%
HR
RT: 2-4 sets of 6-12RM
A
Legend: 1-RM, 1-repetition maximum; Add, Adherece, ADT, Androgen deprivation therapy; AT, Aerobic training; Att, Attendance; BAL, balance exercises; BMI,

Body mass index; Comp, Compliance; FLX, Flexibility training; GnRH, Gonadotrophin-releasing hormone; NHMRC, National Health and Medical Research

D
Council; NR, Not reported; PSA, Prostate-specific antigen; RT, Resistance training; UC, Usual care control group; VO2peak, Peak Oxygen Uptake

TE
EP
C
C
A
 (SDC 3) Table S3. Risk of bias of included studies.

Deviation from
Randomisation Missing outcome Measurement of Selection of the Overall
Outcome intended

D
process data the outcome reported result bias
interventions
Body composition, n= 15
Low risk 15 (100%) 15 (100%) 15 (100%) 13 (86.7%) 15 (100%) 13 (86.7%)
Some concerns 0 0 0 2 (13.3%) 0 2 (13.3%)

TE
High risk 0 0 0 0 0 0
Functional capacity, n= 13
Low risk 12 (92.3%) 13 (100%) 13 (100%) 3 (23.1%) 13 (100%) 3 (23.1%)
Some concerns 1 (7.7%) 0 0 10 (76.9%) 0 10 (76.9%)
High risk 0 0 0 0 0 0
Cardiorespiratory fitness, n= 5

EP
Low risk 5 (100%) 5 (100%) 5 (100%) 3 (60.0%) 4 (80.0%) 2 (40.0%)
Some concerns 0 0 0 2 (40.0%) 1 (20.0%) 3 (60.0%)
High risk 0 0 0 0 0 0
Muscle strength, n= 13
Low risk 12 (92.3%) 13 (100%) 13 (100%) 2 (15.4%) 13 (100%) 2 (15.4%)
Some concerns 1 (7.7%) 0 0 11 (84.6%) 0 11 (84.6%)
High risk 0 0 0 0 0 0
C
PSA, n= 8
Low risk 8 (100%) 8 (100%) 8 (100%) 8 (100%) 8 (100%) 8 (100%)
Some concerns 0 0 0 0 0 0
High risk 0 0 0 0 0 0
C
BMI, n= 6
Low risk 5 (83.3%) 6 (100%) 6 (100%) 6 (100%) 6 (100%) 5 (83.3%)
Some concerns 1 (16.7%) 0 0 0 0 1 (16.7%)
High risk 0 0 0 0 0 0
A

Legend: BMI, Body mass index; n, number of studies; PSA, Prostate-specific antigen.
 D
TE
EP
C
C
A

(SDC 4) Figure S1. Individual risk of bias assessment at outcome level for A) body

composition, B) functional capacity, C) cardiorespiratory fitness, D) muscle strength, E)

prostate-specific antigen and F) body mass index. Green circles, low risk; yellow circles, some

concerns; red circles, high risk of bias.

 (SDC 5) Table S4. Overall and subgroup analysis effects on body composition, functional
capacity, and the secondary outcomes in prostate cancer patients.

Outcomes Analysis n Sample Mean difference 95% CI I2 P-value

Body composition
All# 10 603 -1.0 -1.3 to -0.6 29.1% <.001
Body fat, %
Low risk# 10 603 -1.0 -1.3 to -0.6 29.1% <.001
All 15 917 -0.6 -0.8 to -0.3 0% <.001
Fat mass, kg
Low risk 13 825 -0.6 -0.8 to -0.3 0% <.001
All# 7 490 -0.3 -0.6 to -0.0 26.9% .025
Trunk fat mass, kg
Low risk#

D
7 490 -0.3 -0.6 to -0.0 26.9% .025
All 14 914 0.5 0.3 to 0.7 0% <.001
Lean mass, kg
Low risk 13 825 0.5 0.3 to 0.7 0% <.001
All† 9 578 0.4 0.2 to 0.6 47.0% <.001
Appendicular lean mass, kg

TE
Low risk † 9 578 0.4 0.2 to 0.6 47.0% <.001
Functional capacity
30 seconds sit-to-stand-up, All 3 220 2.8 1.7 to 4.0 45.2% <.001
reps Low risk ǂ - - - - - -
All 5 325 -1.0 -1.4 to -0.6 0% <.001
Repeated sit-to-stand, sec
Low risk ǂ - - - - - -
All† 8 519 -8.3 -12.4 to -4.2 7.0% <.001
EP
400-m walk, sec
Low risk ǂ - - - - - -
All 4 189 -0.2 -0.5 to 0.1 85.4% .225
6-m usual walk, sec
Low risk ǂ - - - - - -
All# 3 140 -0.1 -0.2 to -0.0 0% .040
6-m fast walk, sec
Low risk ǂ - - - - - -
All 3 102 -0.3 -0.8 to 0.2 52.4% .261
Timed-up and go, sec
Low risk ǂ - - - - - -
C

All 4 213 -0.2 -0.3 to -0.1 0% .008

Stair climb, sec
Low risk ǂ - - - - - -
Secondary outcomes
All†
C

5 331 1.3 0.8 to 1.7 0% <.001

VO2peak, ml.kg.min-1
Low risk ǂ - - - - - -
All# 10 728 3.9 2.9 to 4.9 0% <.001
Chest press, kg
Low risk ǂ - - - - - -
A

All# 6 399 8.8 6.9 to 10.7 0% <.001

Leg extension, kg
Low risk ǂ - - - - - -
All 11 769 23.5 15.2 to 31.7 77.4% <.001
Leg press, kg
Low risk ǂ - - - - - -
All# 4 321 5.2 3.9 to 6.5 0% <.001
Seated row, kg
Low risk ǂ - - - - - -
All 6 418 0 -0.2 to 0.2 0% .735
BMI, kg.m-2
Low risk 5 299 0.1 -0.1 to 0.3 0% .440
All 8 576 0.1 -0.2 to 0.3 0% .586
PSA, ng.ml-1
Low risk 8 576 0.1 -0.2 to 0.3 0% .586
#, Adjustment after sensitivity analysis omitting one study at a time. †, Trim-and-fill adjustment

after significant effect of publication bias in egger’s test. ǂ, Insufficient data for analysis. BMI,

Body mass index; n, Number of comparisons; PSA, Prostate-specific antigen; VO2peak, Peak

Oxygen Uptake.

D
TE
EP
C
C
A
(SDC 6) Table S5. Univariate meta-regression on main outcomes mean difference and exercise type, resistance training duration,
weekly volume and peak intensity.
Outcomes n RT components Range Coeff ± SE 95% CI P-value
Body composition

D
11 Type RT alone/ RT combined 0.1±0.5 -1.0 to 1.1 .888
11 Training duration, wk 12 to 48 -0.0±0.03 -0.07 to 0.07 .965
Body fat, %
11 RT weekly volume, reps 306 to 975 -0.0±0.001 -0.002 to 0.001 .650
10 RT intensity, 1-RM 70 to 85% 0.05±0.06 -0.1 to 0.2 .456

TE
15 Type RT alone/ RT combined -0.3±0.3 -1.0 to 0.5 .458
15 Training duration, wk 12 to 48 -0.01±0.02 -0.06 to 0.04 .628
Fat mass, kg
14 RT weekly volume, reps 306 to 975 0.001±0.001 -0.0 to 0.003 .139
14 RT intensity, 1-RM 60 to 85% -0.004±0.03 -0.06 to 0.06 .897
8 Type RT alone/ RT combined -0.5±0.3 -1.4 to 0.3 .149
8 Training duration, wk 12 to 48 -0.03±0.02 -0.08 to 0.02 .158
Trunk fat mass, kg

EP
8 RT weekly volume, reps 306 to 682 0.002±0.001 -0.001 to 0.004 .129
8 RT intensity, 1-RMǂ 80 to 85% - - -
14 Type RT alone/ RT combined -0.3±0.3 -1.0 to 0.3 .303
14 Training duration, wk 12 to 48 -0.01±0.02 -0.05 to 0.02 .385
Lean mass, kg
13 RT weekly volume, reps 306 to 975 -0.0±0.001 -0.002 to 0.001 .819
14 RT intensity, 1-RM 60 to 85% -0.0±0.01 -0.02 to 0.02 .965
9 Type RT alone/ RT combined -0.3±0.2 -0.7 to 0.05 .076
C
Appendicular lean 9 Training duration, wk 12 to 24 -0.03±0.01 -0.06 to 0.003 .075
mass, kg 9 RT weekly volume, reps 320 to 975 0.0±0.001 -0.001 to 0.002 .589
9 RT intensity, 1-RMǂ 80 to 85% - - -
Functional capacity
C
8 Type RT alone/ RT combined 7.7±5.9 -6.7 to 22.2 .239
8 Training duration, wk 12 to 24 -0.8±0.7 -2.5 to 1.0 .332
400-m walk, sec
8 RT weekly volume, reps 270 to 975 0.02±0.02 -0.02 to 0.05 .341
8 RT intensity, 1-RM 75 to 87% -0.7±0.5 -1.9 to 0.5 .182
A

Secondary outcomes
5 Type RT alone/ RT combined -0.3±0.6 -2.3 to 1.6 .630
VO2peak, ml.kg.min-1
5 Training duration, wk 12 to 24 0.0±0.0 -0.1 to 0.2 .651
 4 RT weekly volume, reps 305 to 720 0.0±0.0 -0.1 to 0.1 .598
3 RT intensity, 1-RM 70 to 85% -0.0±0.0 -0.6 to 0.5 .614

11 Type RT alone/ RT combined -6.1±1.9 -10.4 to -1.9 .010

D
11 Training duration, wk 12 to 48 -0.02±0.1 -0.3 to 0.3 .907
Chest press, kg
10 RT weekly volume, reps 135 to 504 0.02±0.01 -0.01 to 0.04 .110
10 RT intensity, 1-RM 70 to 85% -0.6±0.1 -0.9 to -0.4 <.001
7 Type RT alone/ RT combined -0.6±3.1 -8.7 to 7.4 .851

TE
7 Training duration, wk 12 to 24 0.1±0.2 -0.5 to 0.6 .738
Leg extension, kg
6 RT weekly volume, reps 135 to 324 -0.03±0.01 -0.06 to -0.002 .043
6 RT intensity, 1-RMǂ 80 to 85% - - -
11 Type RT alone/ RT combined -21.2±10.2 -44.4 to 1.9 .068
11 Training duration, wk 12 to 48 -0.8±0.6 -2.1 to 0.6 .220
Leg press, kg
10 RT weekly volume, reps 149 to 379 0.1±0.1 -0.0001 to 0.3 .050
10 RT intensity, 1-RM 70 to 85% 0.3±1.4 -2.9 to 3.5 .854

EP
5 Type RT alone/ RT combined -14.9±2.9 -24.1 to -5.6 .014
5 Training duration, wk 12 to 24 -0.3±0.5 -2.0 to 1.4 .624
Seated row, kg
5 RT weekly volume, reps 160 to 683 0.03±0.01 0.01 to 0.05 .032
5 RT intensity, 1-RMǂ 83 to 85% - - -
ǂ, insufficient data for analysis; 1-RM, 1-repetition maximum; 95% CI, 95% confidence intervals; BMI, Body mass index; Coeff,

Meta-regression coefficient; n, Number of comparisons; PSA, Prostate-specific antigen; RT, Resistance training; SE, Standard error;
C
VO2peak, Peak Oxygen Uptake; wk, Weeks.
C
A
 (SDC 7) Table S6. Multivariate meta-regression on main outcomes mean difference and exercise type, resistance training duration,
weekly volume and peak intensity.

Outcomes n RT components Range Coeff ± SE 95% CI P-value Model

D
Body composition
10 Type RT alone/ RT combined -1.0±0.9 -3.4 to 1.4 .326
r2=-73.0%
10 Training duration, wk 12 to 48 -0.01±0.03 -0.1 to 0.1 .799
Body fat, % I2=44.3%
10 RT weekly volume, reps 306 to 975 -0.002±0.002 -.01 to 0.0 .359

TE
P=.785
10 RT intensity, 1-RM 70 to 85% 0.05±0.07 -0.1 to 0.2 .544
13 Type RT alone/ RT combined 0.15±0.5 -1.0 to 1.3 .771
r2=-77.9%
13 Training duration, wk 12 to 48 -0.01±0.03 -0.08 to 0.06 .780
Fat mass, kg I2=13.2%
13 RT weekly volume, reps 306 to 975 0.001±0.001 -0.002 to 0.004 .334
P=.777
13 RT intensity, 1-RM 60 to 85% 0.002±0.06 -0.14 to 0.14 .977
8 Type RT alone/ RT combined -0.08±0.5 -1.6 to 1.4 .896
r2=43.0%

EP
8 Training duration, wk 12 to 48 -0.02±0.02 -0.09 to 0.04 .344
Trunk fat mass, kg I2=33.5%
8 RT weekly volume, reps 306 to 682 0.001±0.002 -0.004 to 0.01 .467
P=.334
8 RT intensity, 1-RMǂ 80 to 85% - - -
13 Type RT alone/ RT combined -0.7±0.5 -1.8 to 0.4 .162
r2=100%
13 Training duration, wk 12 to 48 -0.01±0.02 -0.06 to 0.03 .449
Lean mass, kg I2=0%
13 RT weekly volume, reps 306 to 975 -0.002±0.001 -0.004 to 0.001 .207
P=.386
13 RT intensity, 1-RM 60 to 85% 0.03±0.05 -0.1 to 0.2 .522
C
9 Type RT alone/ RT combined -0.3±0.3 -1.1 to 0.4 .299
r2=100%
Appendicular lean 9 Training duration, wk 12 to 24 -0.02±0.02 -0.06 to 0.03 .361
I2=0%
mass, kg 9 RT weekly volume, reps 320 to 975 -0.0±0.0 -0.002 to 0.001 .657
P=.203
9 RT intensity, 1-RMǂ 80 to 85% - - -
C
Functional capacity
8 Type RT alone/ RT combined 9.5±5.4 -7.6 to 26.7 .175
r2=100%
8 Training duration, wk 12 to 24 -0.6±0.8 -3.0 to 1.9 .500
400-m walk, sec I2=0%
8 RT volume, weekly reps 270 to 975 -0.01±0.03 -0.1 to 0.1 .794
A

P=.358
8 RT intensity, 1-RM 75 to 87% -1.0±1.0 -4.1 to 2.1 .392
Secondary outcomes
10 Type RT alone/ RT combined -2.9±1.5 -6.6 to 0.8 .104 r2=100%
Chest press, kg
10 Training duration, wk 12 to 48 -0.03±0.1 -0.3 to 0.2 .746 I2=0%
 10 RT volume, weekly reps 135 to 504 -0.0±0.01 -0.02 to 0.02 .959 P= .012
10 RT intensity, 1-RM 70 to 85% -0.5±0.2 -0.9 to -0.1 .022
6 Type RT alone/ RT combined -3.7±3.2 -17.4 to 10.0 .366
r2=100%
6 Training duration, wk 12 to 24 -0.3±0.2 -1.2 to 0.6 .313
Leg extension, kg I2=0%

D
6 RT volume, weekly reps 135 to 324 -0.04±0.02 -0.1 to 0.02 .087
P=.204
6 RT intensity, 1-RMǂ 80 to 85% - - -
10 Type RT alone/ RT combined -68.4±44.0 -181.5 to 44.6 .181
r2=88.2%
10 Training duration, wk 12 to 48 -0.4±0.6 -1.9 to 1.1 .498
Leg press, kg I2=57.4%

TE
10 RT volume, weekly reps 149 to 379 -0.2±0.2 -0.8 to 0.3 .375
P=.147
10 RT intensity, 1-RM 70 to 85% 3.2±2.2 -2.4 to 8.8 .205
ǂ, insufficient data for analysis; 1-RM, 1-repetition maximum; 95% CI, 95% confidence intervals; BMI, Body mass index; Coeff,

Meta-regression coefficient; I2= Statistical test of heterogeneity; n, Number of comparisons; PSA, Prostate-specific antigen; r2,

Adjusted coefficient of determination; RT, Resistance training; SE, Standard error; VO2peak, Peak Oxygen Uptake; wk, Weeks

EP
C
C
A