Citation: Hughes S, Egger S, Carle C, Smith DP, Chambers S, Kahn C, et al. (2019) Factors associated with the use of diet and the use of Objective exercise for prostate cancer by long-term survivors. PLoS ONE 14(10): e0223407. https:// To assess the use of diet and the use of exercise for prostate cancer (and/or its treatments’ doi.org/10.1371/journal.pone.0223407 side effects) by long-term survivors and whether such use is associated with selected socio- Editor: Justin C. Brown, Pennington Biomedical demographic, clinical, health-related quality-of-life (HRQOL) and psychological factors. Research Center, UNITED STATES Received: July 19, 2019 Design, setting and participants Accepted: September 21, 2019 Population-based cohort study in New South Wales, Australia of prostate cancer survivors Published: October 3, 2019 aged<70 years at diagnosis and who returned a 10-year follow-up questionnaire. Peer Review History: PLOS recognizes the benefits of transparency in the peer review Methods process; therefore, we enable the publication of Validated instruments assessed patient’s HRQOL and psychological well-being. Poisson all of the content of peer review and author responses alongside final, published articles. The regression was used to estimate adjusted relative proportions (RRs) of prostate cancer sur- editorial history of this article is available here: vivor groups who were currently eating differently (‘using diet’) or exercise differently (‘using https://doi.org/10.1371/journal.pone.0223407 exercise’) to help with their prostate cancer. Copyright:© 2019 Hughes et al. This is an open access article distributed under the terms of the Results Creative Commons Attribution License, which permits unrestricted use, distribution, and 996 (61.0% of 1634) participants completed the 10-year questionnaire of whom 118 (11.8%; reproduction in any medium, provided the original 95%CI[9.8–13.9]) were using diet and 78 (7.8%; 95%CI[6.2–9.5]) were using exercise to author and source are credited. help with their prostate cancer. Men were more likely to use diet or use exercise for prostate Data Availability Statement: Data used in this cancer if they were younger (p-trend = 0.020 for diet, p-trend = 0.045 for exercise), more study are partially restricted for use because of educated (p-trend<0.001, p-trend = 0.011), support group participants (p-nominal<0.001, restrictions imposed by ethical approval, the research aims governing the study and consent p-nominal = 0.005), had higher Gleason score at diagnosis (p-trend<0.001, p-trend = 0.002) PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 1 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors agreements with study participants. The data is and had knowledge of cancer spread (p-nominal = 0.002, p-nominal = 0.001). Use of diet available through an application to the Cancer was also associated with receipt of androgen deprivation therapy (RR = 1.59; 95%CI[1.04– Council NSW Cancer Research Division and with 2.45]), a greater fear of cancer recurrence (p-trend = 0.010), cognitive avoidance (p-trend = approval from the Cancer Council NSW Ethics 0.025) and greater perceived control of cancer course (p-trend = 0.014). Use of exercise Committee. Researchers who wish to access data owned or held by Cancer Council NSW must hold was also associated with receipt of prostatectomy (RR = 2.02; 95%CI[1.12–3.63]), receipt all relevant ethics approvals before access can be of androgen deprivation therapy (RR = 2.20; 95%CI[1.34–3.61]) and less satisfaction with granted. Researchers may be required to enter into medical treatments (p-trend = 0.044). a Data Transfer Agreement. To find out how to access data please contact the Cancer Research Division at firstname.lastname@example.org. Details and Conclusions contact information are available at https://www. cancercouncil.com.au/research/for-researchers/ Few long-term prostate cancer survivors use diet or exercise to help with their prostate can- ethics/. The data custodian for the NSW Prostate cer. Survivors may benefit from counselling on the scientific evidence supporting healthy Cancer Care and Outcomes Study is Cancer eating and regular exercise for improving quality-of-life and cancer-related outcomes. Council NSW. Funding: This work was supported by the Prostate Cancer Foundation of Australia (PG40) (to DLO’C). DPS was supported by a Career Development Fellowship from the Cancer Institute NSW (#15/ CDF/1-10). Introduction Competing interests: The authors have declared Worldwide, prostate cancer is the second most common cancer for men and the fourth most that no competing interests exist. common cancer overall . In higher-income countries where prostate specific antigen (PSA) testing is common, substantial numbers of men are living with a diagnosis of prostate cancer and the adverse consequences (e.g., incontinence, erectile dysfunction, pain, psychological dis- tress) that can persist for many years after diagnosis [2–3]. In New South Wales (NSW), Aus- tralia’s most populous state, the number of men living with prostate cancer was estimated to have risen by at least 59% (>22,500 extra prevalent cases) in the ten years from 2007 to 2017 . Given the significant and increasing prevalent pool, there is growing interest in lifestyle modifications that might help reduce the risk of prostate cancer progression and improve prostate cancer treatment related quality-of-life . Because poor diet and lack of physical activity are thought to play a role in the development of cancer , it seems plausible that these factors may also play a role in the progression of can- cer, including prostate cancer. In terms of diet, three randomised controlled trials (RCTs) [6– 8]—each judged to be at low risk of bias and of high methodological quality —demon- strated that certain dietary interventions might improve markers of prostate cancer progres- sion. Limited evidence from observational studies has also suggested that engaging in healthy dietary practices (e.g., increased fruit and vegetable consumption, reduced total and saturated fat consumption) may help in reducing prostate cancer progression [10–11]. With regards to exercise, there appears to be little or no evidence from RCTs that changes in physical activity levels slow prostate cancer progression, but evidence of this effect has been found in observa- tional studies [12–14]. For other outcomes, evidence from RCTs suggests that various physical activity interventions can improve physical functioning, physical fitness, muscular strength, body composition and quality of life for patients receiving androgen deprivation therapy (ADT) [15–17]. In addition to the possible benefits of a healthy diet and physical activity on prostate cancer related outcomes, survivors potentially receive additional health benefits unre- lated to their cancer, such as reduced risks of cardiovascular disease  and additional pri- mary cancers . Taking into account the available evidence and expert clinical opinion, the American Can- cer Society Prostate Cancer Survivorship Care Guidelines (ACSSCG)  recommend that diets for prostate cancer survivors should—among other things—emphasise vegetables, fruits PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 2 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors and foods with low amounts of saturated fat, while consuming adequate, but not excessive, amounts of dietary sources of calcium. In the absence of physical limitations or contraindica- tions, the ACSSCG recommend that survivors should aim for at least 75 or 150 minutes per week of vigorous or moderate intensity exercise, respectively. The ACSSCG also recommend that survivors with post-prostatectomy incontinence be referred to a physical therapist for pel- vic floor rehabilitation. Despite these recommendations, few previous quantitative studies have examined the die- tary and exercise changes that prostate cancer survivors actually adopt to help with their cancer or its treatments’ side effects. In this cross-sectional analysis, we used information from a group of long-term survivors of prostate cancer (mean = 10 years) from NSW, to describe the use of diet and the use of exercise “for prostate cancer and/or its treatments’ side effects” (here- after abbreviated as “for prostate cancer”) and whether such use was associated with selected socio-demographic, clinical, health-related quality-of-life (HRQOL) and psychological factors. We also discuss the cohort’s use of diet and exercise for prostate cancer in comparison to their use of complementary and alternative medicines (CAMs) for prostate cancer—the latter hav- ing been reported in detail in a previous publication . Materials and methods Study sample The New South Wales Prostate Cancer Care and Outcomes Study (PCOS) is a population- wide longitudinal cohort study conducted in NSW, Australia, with a primary objective of assessing the effects of various treatments on HRQOL after a prostate cancer diagnosis. A total of 3195 men aged less than 70 years with histopathologically confirmed T1-4 prostate cancer diagnosed between October 2000 and October 2002 were identified through the NSW Cancer Registry and, after verbal informed consent had been given by their doctor, were invited to participate in PCOS. Of these patients, 1995 completed a baseline questionnaire (S1 Fig) after providing written informed consent. By January 2011, 1634 men were still alive, and 1427 of these men remained in PCOS and were invited to participate in a 10-year follow-up question- naire (mean of 10 years after diagnosis; range 9–12 years). The 10-year questionnaire assessed various HRQOL and psychological outcomes for participants and their use of diet and exercise for prostate cancer (participants were also asked about their use of CAMs for prostate cancer and the corresponding results were reported in a previous publication ). Of the 1634 men, 996 (61%) completed and returned the 10-year questionnaire. Additional details of the initial recruitment process for PCOS are provided elsewhere [21–22]. PCOS was approved by the human research ethics committees of Cancer Council NSW, the Cancer Institute NSW, and the NSW Department of Health. The 10-year follow-up questionnaire was approved by the Cancer Council NSW Human Research Ethics Committee (Approval number: 2010#244). Data collection Clinical and socio-demographic data. Clinical data relating to diagnosis and primary treatment were collected for each participant by either a trained field worker or the treating doctor using a data collection form and protocol. These data were collected between 12 and 24 months after the histological diagnosis of prostate cancer and included prostate-specific antigen (PSA) level at diagnosis, Gleason score and clinical stage at diagnosis, and treatment received within 12 months of diagnosis. Place and socio-economic status of each man’s resi- dence at diagnosis were based on the Accessibility/Remoteness Index of Australia (ARIA+)  and the Socio-Economic Indexes for Areas (SEIFA)  respectively. Highest level of education completed was self-reported in the baseline questionnaire. Information on prostate PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 3 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors cancer treatments received was obtained from the treating doctors’ records (diagnosis to 12 months) and from linked administrative health datasets (covering from diagnosis to ten- year follow-up). For each man who provided written informed consent, treatment data were obtained from Medicare Australia and NSW Health’s Admitted Patient Data Collection . Clinical and socio-demographic information obtained in the 10-year questionnaire included current place of residence, employment status, marital status, support group participation and self-report of whether the cancer had spread. Psychological and health-related quality-of-life measures. A number of previously vali- dated psychological and HRQOL patient-reported outcome measures (PROMs) were included in the 10-year questionnaire including (Table 1): a 6-item course of cancer subscale from the Cancer Locus of Control scale measuring the man’s perceived control of the course of their cancer ; Kornblith’s 5-item Cancer Fear of Recurrence scale ; the 22-item Impact of Event Scale-Revised (IES-R)  measuring distress, hyperarousal, intrusive thinking and cognitive avoidance associated with having prostate cancer; the 14-item Hospital Anxiety and Depression Scale (HADS)  measuring anxiety and depression; the 26-item Expanded Pros- tate cancer Index Composite Short Form (EPIC-26)  measuring urinary incontinence, uri- nary irritative/obstructive, bowel, sexual and hormonal summary scores, and also measuring urinary, bowel and sexual bother scores from the University of California-Los Angeles Prostate Cancer Index (UCLA-PCI) ; and the 12-item Short Form-12 (SF-12)  scale measuring Table 1. Psychological and health-related quality-of-life patient-reported outcome measures included in the 10-year questionnaire. Patient-reported outcome measure Domain/scale/subscale Cancer Locus of Control Perceived control of the course of cancer Kornblith’s Fear of Cancer Recurrence Fear of cancer recurrence IES-R Prostate cancer specific distress IES-R Prostate cancer specific hyperarousal IES-R Prostate cancer specific intrusive thinking IES-R Prostate cancer specific cognitive avoidance HADS Anxiety HADS Depression EPIC-26 Urinary incontinence summary EPIC-26 Urinary irritative/obstructive summary EPIC-26 Bowel summary EPIC-26 Sexual summary EPIC-26 Hormonal summary UCLA-PCI Urinary bother UCLA-PCI Bowel bother UCLA-PCI Sexual bother EPIC-50 Satisfaction with medical treatment SF-12 Mental component score SF-12 Physical component score EPIC-26 = Expanded Prostate cancer Index Composite Short Form UCLA-PCI = University of California-Los Angeles Prostate Cancer Index HADS = Hospital Anxiety and Depression Scale IES-R = Impact of Event Scale-Revised EPIC-50 = Expanded Prostate cancer Index Composite Long Form (EPIC-50) SF-12 = Short Form-12 https://doi.org/10.1371/journal.pone.0223407.t001 PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 4 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors the mental and physical dimensions of HRQOL. Satisfaction with medical treatments was ascertained on a 1-item 5-point Likert scale from the Expanded Prostate cancer Index Com- posite Long Form (EPIC-50) . For each psychological domain, higher scores indicate higher levels of the psychological attribute. For each HRQOL domain, higher scores indicate better HRQOL (which corresponds to less bother for the bother domains assessing bother). Diet and exercise changes. Men were asked whether they had “ever” made a change to their diet to help with their prostate cancer and/or its treatments’ side effects. If they answered yes they were then asked whether they were “currently” eating differently to help with their prostate cancer and/or its treatments’ side effects. Participants were asked about their specific dietary changes with available response options being: increased/decreased fruit, soy products, vegetables, dairy, fats, oils, fried foods, processed meats, red meat, dairy products plus free- text fields for user–specified options. Men were also asked whether they had “ever” made a change to the exercise they do to help with their prostate cancer and/or its treatments’ side effects. If they answered yes they were then asked whether they were “currently” exercising dif- ferently to help with their prostate cancer and/or its treatments’ side effects. Participants were asked to describe any changes in exercise and these free-text fields were subsequently coded for analysis. Statistical methods Poisson regression with robust variance estimation  was used to estimate the adjusted rela- tive proportions (RRs) of current diet use and current exercise use for prostate cancer accord- ing to socio-demographic characteristics, clinical characteristics, psychological and HRQOL domains. The dependent variables for all regressions were current diet use for prostate cancer (yes or no) and current exercise use for prostate cancer (yes or no). Independent variables included age at completion of the 10-year questionnaire (<65, 65–69, 70–74, 75+ years; age ranged from 52 to 80 years), education (university or college degree, high school, less than high school), socio-economic status of place of residence (divided into quintiles using SEIFA), place of residence (major city, inner regional, outer regional/ remote/ very remote based on ARIA+), health insurance (private health insurance- with extras, private health insurance- without extras, Medicare only), employment status (in full time paid work, in part time paid work, retired/unemployed, self-employed), married or in defacto partner relationship (no, yes), participation in a support group (no contact with support groups, receive newsletter only, participate regularly or occasionally), country of birth (Australia, elsewhere), overall cancer severity at diagnosis (localised low risk, localised intermediate risk, localised high risk, stage T3-4, unknown)  and treatments used since diagnosis (active surveillance/watchful waiting (AS/WW), prostatectomy, external beam radiotherapy (EBRT)/ brachytherapy, ADT, bone- EBRT/chemotherapy/bisphosphonates). Other independent variables included PSA level at diagnosis (<4, 4 to <10, 10 to <20, 20+ng/mL, unknown), Gleason score at diagnosis (<7, 7, >7, unknown), clinical stage at diagnosis (T1a-c, T2a-c, T3a-c/T4a, unknown), and knowledge of cancer spread (no, yes). In order to avoid collinearity, however, these other variables were not included in models simultaneously with overall cancer severity at diagnosis. Subjects with missing data on any independent variable were excluded from regression analyses, but ‘unknown’ test results for clinical variables were analysed as distinct categories (because ‘unknown’ test results are primarily due to the absence of testing and thus the result is ‘unknown’ to the subject). Tests for linear trends were performed by inclusion of continuous/ ordinal versions of independent variables where appropriate. For ordinal variables that were not interval scaled (eg. health insurance), consecutive integers were used for coding when test- ing for linear trends. Psychological and HRQOL variables were included one at a time as linear PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 5 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors continuous independent variables in regression models after standardising each variable to have variance equal to one. Hence, RRs for psychological and HRQOL variables indicate the change in the probabilities of using diet or of using exercise per standard deviation increase in the variable . Subjects with missing data for any psychological or HRQOL domain were excluded from analyses relating to that particular domain. Sensitivity analyses were conducted to assess whether estimates were unduly affected by missing data. In these analyses, multiple imputation was used to impute missing 10-year data for the 638 surviving PCOS participants who did not complete the 10-year questionnaire. Missing data were also multiply imputed for participants who completed the 10-year question- naire but had missing data for one or more variables. Data were imputed 100 times using the method of chained equations . Variables in the imputation models were the dependent and independent variables in the original multivariable regression models plus baseline socio- economic status of place of residence, place of residence, employment status, health insurance and marital status (age, education, and country of birth at the 10-year follow-up were esti- mated directly from corresponding baseline values). The combined imputed and original data were then analysed using estimation techniques for multiply imputed data. Results Of the 996 men who returned a 10-year follow-up questionnaire, 134 (13.5%; 95%CI[11.3– 15.6])) had ever changed their diet and 102 (10.2%; 95%CI[8.4–12.1])) had ever changed the exercise they do to help with their prostate cancer (Table 2). Of the 996 men, 118 (11.8% 95% CI[9.8–13.9]) were currently using diet and 78 (7.8%%; 95%CI[6.2–9.5]) were currently using exercise for their prostate cancer. The most common dietary and exercise changes were the same for ‘ever’ use and ‘current’ use including ‘more vegetables’, ‘more fruit’, ‘less processed Table 2. Types of diet and exercise changes ever and currently used for prostate cancer and/or its treatments’ side effects. Ever Currently Diet and exercise changes for prostate cancer and/or treatments’ side effects^ n (% of 996) n (% of 996) Changes to diet, exercise or both 193 (19.4) 158 (15.9) Diet changes: 134 (13.5) 118 (11.8) More fruit 86 (8.6) 79 (7.9) More soy products 37 (3.7) 30 (3.0) More vegetables 91 (9.1) 87 (8.7) Less dairy 49 (4.9) 48 (4.8) Less fats, oils or fried foods 61 (6.1) 60 (6.0) Less processed meats 71 (7.1) 71 (7.1) Less red meat 66 (6.6) 63 (6.3) Exercise changes: 102 (10.2) 78 (7.8) More walking 44 (4.4) 40 (4.0) More aerobic exercise (other than walking) 15 (1.5) 13 (1.3) Pelvic floor exercises 33 (3.3) 19 (1.9) Resistance exercises 10 (1.0) 7 (<1%) Unspecified gym activities 18 (1.8) 13 (1.3) Categories of specific diet and exercise changes are listed if ever used by over 1% of men. ^ Men may have more than one type of diet and or exercise change Unspecified gym activities may include “more aerobic exercise”, “pelvic floor exercises” and/or “resistance exercises” (hence numbers for these categories are likely to be underestimates). https://doi.org/10.1371/journal.pone.0223407.t002 PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 6 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors meat’, ‘more walking’, and ‘pelvic floor exercises’. A commonly reported reason for both cur- rently using diet and currently using exercise was ‘to make me feel better’ (45% and 58% of current users respectively) (S1 Table). Current diet users also frequently cited ‘to boost my immune system’ (46% of current users), ‘to prevent cancer returning or spreading’ (46%) and ‘to do as much as I can for myself’ (46%) as reasons. Relatively few of the men using exercise for their prostate cancer (1 in 4) indicated that information about exercise came from their doctor. Men were more likely to currently use diet or currently use exercise for prostate cancer if they were younger (p-trend = 0.020 for diet, p-trend = 0.045 for exercise), more educated (p-trend<0.001, p-trend = 0.011), support group participants (p-nominal<0.001, p-nomi- nal = 0.005) (Table 3), had higher Gleason score at diagnosis (p-trend<0.001, p-trend = 0.002) (Table 4) or had knowledge of cancer spread (p-nominal = 0.002, p-nominal = 0.001). Men were more likely to currently use exercise if they had received a prostatectomy (RR = 2.02; 95% CI[1.12–3.63]) or ADT (RR = 2.20; 95%CI[1.34–3.61]) (Table 3), and were more likely to cur- rently use diet if they had ever received ADT (RR = 1.59; 95%CI[1.04–2.45]). PSA level was also associated with use of exercise (p-nominal = 0.024), but the difference was driven by the ‘unknown’ category and not related to clinical levels (Table 4). For the psychological domains, diet was more likely to be currently used by men who reported a greater fear of cancer recurrence (RR = 1.25; 95%CI[1.05–1.47]), cancer-specific cognitive avoidance (RR = 1.21; 95%CI[1.02–1.42]) and perceived control of cancer course (RR = 1.25; 95%CI[1.05–1.50]) (Fig 1). Current use of exercise was associated with less satisfac- tion with medical treatments (RR = 0.83; 95%CI[0.69–1.00]) (Fig 1). Analyses using the multiply-imputed data produced marginally, but not materially, higher estimates for prevalences of current diet and exercise use (S2 Table). The estimated magni- tudes of associations from the original analyses were not materially different from those obtained from analyses using the multiply-imputed data (S2–S4 Tables, S2 and S3 Figs). Discussion A cancer diagnosis is often considered to be a ‘teachable moment’ in which patients may be inclined to seek information about lifestyle changes that might improve cancer outcomes and quality-of-life. In this cohort of long-term prostate cancer survivors, however, only about one in seven men had ever made changes to their diet and only one in ten men had ever made changes to the exercise they do to help with their prostate cancer. In terms of the specific die- tary and exercise changes adopted by more than 1% of the cohort (Table 2), most were broadly consistent with recommendations outlined in the ACSSCG , and none were unequivocally contraindicated by these guidelines. Younger, more educated survivors and those who partici- pate in support groups were more likely to currently use diet or exercise to help with their prostate cancer. ADT recipients were more likely to currently use diet or exercise than non- recipients, while prostatectomy recipients were more likely to currently use exercise than non- recipients. Psychological distress also appeared to be a motivator for diet and exercise use with current diet users having greater fear of recurrence and cognitive avoidance than non-users, while current exercise users were less satisfied with their medical treatments than non-users. A number of previous studies have reported on the prevalence of dietary and exercise behaviours among prostate cancer survivors [38–44]. In a 2008 systematic review , investi- gators found that the prevalence of physically active prostate cancer survivors was less than 30% in some study cohorts. With regards to diet, two U.S surveys [38–39] reported that only about 1/3 of prostate cancer survivors were meeting the American Cancer Society’s (contem- poraneous) recommendations for fruit and vegetable intake . It is important to note that PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 7 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors Table 3. Associations between current use of diet and exercise for prostate cancer and/or its treatments’ side effects and socio-demographic/clinical characteristics for Australian long-term prostate cancer survivors. Diet Exercise � � Characteristic N Current-user RR p-nominal Current-user RR p-nominal n (%) p-trend^^ n (%) p-trend^^ 996 118 (11.8) 78 (7.8) Age (years) <65 164 24 (14.6) ref. 0.220 17 (10.4) ref. 0.195 65–69 267 37 (13.9) 1.06 (0.67, 1.67) 0.020 19 (7.1) 0.70 (0.37, 1.32) 0.045 70–74 299 28 (9.4) 0.69 (0.41, 1.18) 27 (9.0) 0.88 (0.46, 1.69) 75–80 266 29 (10.9) 0.74 (0.44, 1.24) 15 (5.6) 0.52 (0.26, 1.05) Education University or college degree 297 57 (19.2) ref. <0.001 36 (12.1) ref. 0.023 High school 670 60 (9.0) 0.47 (0.32, 0.67) <0.001 42 (6.3) 0.58 (0.36, 0.93)^ 0.011 Less than high school 25 1 (4.0) 0.25 (0.04, 1.53) 0 (0.0) Missing + 4 0 (0.0) 0 (0.0) Socio-economic status of residence area 1- Highest SES 346 46 (13.3) ref. 0.438 30 (8.7) ref. 0.554 2 204 24 (11.8) 1.13 (0.69, 1.83) 0.914 16 (7.8) 1.30 (0.68, 2.48) 0.288 3 214 21 (9.8) 0.67 (0.38, 1.17) 19 (8.9) 1.01 (0.52, 1.96) 4 144 13 (9.0) 0.96 (0.48, 1.93) 8 (5.6) 0.67 (0.25, 1.77) 5- Lowest SES 83 12 (14.5) 1.24 (0.58, 2.67) 4 (4.8) 0.56 (0.18, 1.77) Missing + 5 2 (40.0) 1 (20.0) Place of residence Major city 580 75 (12.9) ref. 0.934 50 (8.6) ref. 0.237 Inner regional 266 27 (10.2) 0.91 (0.57, 1.48) 0.763 16 (6.0) 0.72 (0.38, 1.33) 0.257 Outer regional/ remote/ very remote 148 15 (10.1) 0.95 (0.48, 1.88) 12 (8.1) 1.36 (0.66, 2.81) Missing + 2 1 (50.0) 0 (0.0) Health insurance Private—with extras 584 75 (12.8) ref. 0.763 55 (9.4) ref. 0.257 Private—without extras 153 16 (10.5) 0.81 (0.47, 1.42) 0.699 9 (5.9) 0.58 (0.28, 1.19) 0.220 Medicare 256 26 (10.2) 0.94 (0.58, 1.50) 14 (5.5) 0.73 (0.38, 1.38) Missing + 3 1 (33.3) 0 (0.0) Employment status In full time paid work 130 18 (13.8) ref. 0.750 9 (6.9) ref. 0.359 In part time paid work 107 12 (11.2) 0.82 (0.41, 1.64) n/a 7 (6.5) 0.94 (0.35, 2.54) n/a Retired/Unemployed 740 83 (11.2) 0.98 (0.60, 1.61) 59 (8.0) 1.60 (0.73, 3.53) Self-employed 17 5 (29.4) 1.46 (0.53, 4.03) 3 (17.6) 2.34 (0.56, 9.78) Missing + 2 0 (0.0) 0 (0.0) Married or living with defacto No 166 20 (12.0) ref. 0.926 13 (7.8) ref. 0.971 Yes 829 98 (11.8) 1.02 (0.63, 1.65) n/a 65 (7.8) 1.01 (0.54, 1.89) n/a Missing + 1 0 (0.0) 0 (0.0) Participate in a support group No contact with support groups 770 76 (9.9) ref. <0.001 46 (6.0) ref. 0.005 Receive newsletter only 153 30 (19.6) 2.13 (1.43, 3.19) n/a 20 (13.1) 2.06 (1.23, 3.45) n/a Participate regularly or occasionally 73 12 (16.4) 1.48 (0.85, 2.59) 12 (16.4) 2.09 (1.14, 3.84) Country of birth In Australia 768 90 (11.7) ref. 0.350 62 (8.1) ref. 0.198 In another country 227 28 (12.3) 0.82 (0.54, 1.24) n/a 16 (7.0) 0.71 (0.42, 1.20) n/a (Continued ) PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 8 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors Table 3. (Continued ) Diet Exercise � � Characteristic N Current-user RR p-nominal Current-user RR p-nominal n (%) p-trend^^ n (%) p-trend^^ Missing + 1 0 (0.0) 0 (0.0) Overall cancer severity at diagnosis† Localised low risk 341 31 (9.1) ref. 0.237 20 (5.9) ref. 0.429 Localised intermediate risk 359 36 (10.0) 1.13 (0.70, 1.82) 0.023 29 (8.1) 1.44 (0.83, 2.51) 0.067 Localised high risk 176 33 (18.8) 1.56 (0.94, 2.58) 16 (9.1) 1.39 (0.73, 2.64) Stage T3-4 68 14 (20.6) 1.91 (0.99, 3.65) 10 (14.7) 2.17 (0.97, 4.87) Unknown 52 4 (7.7) 1.06 (0.39, 2.87) 3 (5.8) 1.27 (0.37, 4.38) Treatments used since diagnosis ^^^ AS/WW 99 13 (13.1) 1.75 (0.94, 3.26) <0.001 # 7 (7.1) 1.81 (0.86, 3.83) <0.001 # Prostatectomy 658 65 (9.9) 0.83 (0.53, 1.30) n/a 56 (8.5) 2.02 (1.12, 3.63) n/a EBRT/Brachytherapy 397 66 (16.6) 1.44 (0.91, 2.27) 37 (9.3) 1.17 (0.69, 1.98) Androgen deprivation therapy 319 60 (18.8) 1.59 (1.04, 2.45) 39 (12.2) 2.20 (1.34, 3.61) � � Other 10 4 (40.0) 2.54 (1.04, 6.21) 3 (30.0) 2.58 (0.88, 7.52) Adjusted for age, education, socio-economic status of residence area, place of residence, health insurance, employment status, marital status, participation in a support group, country of birth, cancer severity at diagnosis, and treatments used since diagnosis; 16 of the 996 participants were excluded from regression analyses due to missing data; Localised (stage 1 or 2) risk groups- low risk (PSA�10, Gleason score�6, and clinical stage = T1-2a), intermediate risk (10<PSA�20, Gleason score = 7 or clinical stage = T2b) high-risk (PSA >20, Gleason score>7, or clinical stage T2c); p-values values correspond to fully adjusted models; ^Groups merged for regression analysis due to zero cell; ^^p-trend analysis excludes ‘missing’ and ‘unknown’ categories; ^^^ Multiple treatments possible for each man and reference group for each treatment is not having had that treatment; p-value is for test that all RRs equal one; � � ‘Other’ group contains 10 patients who received chemotherapy, bisphosphonates and/or bone EBRT; Data from 10-year questionnaire unless “at diagnosis” stated. https://doi.org/10.1371/journal.pone.0223407.t003 these ‘prevalence’ studies are only indirectly related to the current study as we did not collect information on the prevalence of specific dietary and exercise behaviours (ie our data relate to ‘change’ in dietary and exercise behaviours for prostate cancer). The prevalence studies are useful, however, in that they show that some prostate cancer survivorship cohorts have consid- erable room to improve dietary and exercise behaviours in directions more consistent with survivorship guidelines. In addition to the ‘prevalence’ studies mentioned above, another group of studies have reported on ‘change’ in diet and exercise behaviours following prostate cancer diagnosis, but with ‘change’ being for any reason and not necessarily related to the cancer or its treatments’ side effects [47–48]. The distinction between ‘change for any reason’ and ‘change to help with prostate cancer’ is important because individuals–including those who have never been diag- nosed with cancer–often make behavioural changes unrelated to cancer. In our study, for example, only 15.9% of survivors reported currently eating, exercising or doing both differ- ently to help with their prostate cancer and/or its treatments’ side effects (Table 2), yet 51.4% of survivors reported currently eating, exercising or doing both differently for any reason related to improving health and well-being (including to help with prostate cancer). In the cur- rent study, we chose to focus on diet and exercise changes survivors make to help with their prostate cancer because these outcomes capture both men’s willingness to make healthy PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 9 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors Table 4. Associations between current use of diet and exercise for prostate cancer and/or its treatments’ side effects and other clinical characteristics for Australian long-term prostate cancer survivors. Diet Exercise � � Characteristic N+ Current-user RR p-nominal Current-user RR p-nominal n (%) p-trend^^ n (%) p-trend^^ 996 118 (11.8) 78 (7.8) PSA at diagnosis (ng/mL) † <10 652 68 (10.4) ref. 0.826 49 (7.5) ref. 0.024 10 to <20 200 28 (14.0) 1.03 (0.68, 1.58) 0.333 19 (9.5) 1.30 (0.78, 2.18) 0.387 20+ 97 18 (18.6) 0.79 (0.45, 1.39) 7 (7.2) 0.57 (0.24, 1.38) Unknown 47 4 (8.5) 0.78 (0.21, 2.92) 3 (6.4) 0.35 (0.15, 0.82) Gleason score at diagnosis † <7 530 45 (8.5) ref. 0.013 30 (5.7) ref. 0.092 7 353 48 (13.6) 1.43 (0.95, 2.14) <0.001 35 (9.9) 1.43 (0.87, 2.34) 0.002 >7 81 22 (27.2) 2.38 (1.42, 4.00) 10 (12.3) 1.69 (0.85, 3.36) Unknown 32 3 (9.4) 1.35 (0.15, 12.37) 3 (9.4) 3.01 (1.06, 8.52) Clinical stage at diagnosis † T1a-T2a 709 74 (10.4) ref. 0.711 50 (7.1) ref. 0.229 T2b-T2c 185 27 (14.6) 1.06 (0.68, 1.65) 0.404 15 (8.1) 0.98 (0.56, 1.70) 0.350 T3a-c, T4a 68 14 (20.6) 1.37 (0.78, 2.40) 10 (14.7) 1.59 (0.76, 3.30) Unknown 34 3 (8.8) 1.46 (0.22, 9.85) 3 (8.8) 2.30 (0.86, 6.10) Knowledge of cancer spread † No 925 95 (10.3) ref. 0.002 59 (6.4) ref. 0.001 Yes 71 23 (32.4) 2.15 (1.31, 3.51) n/a 19 (26.8) 2.53 (1.45, 4.40) n/a Adjusted for age, education, socio-economic status of residence area, place of residence, health insurance, employment status, marital status, participation in a support group, country of birth, PSA at diagnosis, Gleason score at diagnosis, clinical stage at diagnosis, and treatments used since diagnosis; To avoid collinearity, PSA at diagnosis, Gleason score at diagnosis, clinical stage at diagnosis, knowledge of cancer spread were not included in models simultaneously with overall cancer severity at diagnosis; p-values values correspond to fully adjusted models. ^^p-trend analysis excludes ‘missing’ and ‘unknown’ categories; Data from 10-year questionnaire unless “at diagnosis” stated. 16 of the 996 participants were excluded from regression analyses due to missing data. https://doi.org/10.1371/journal.pone.0223407.t004 lifestyle changes and also their awareness that such changes might help with their prostate cancer. It is important to note, however, that although many survivors in our cohort reported changing eating and exercise habits for reasons unrelated to their cancer, such habits may also help them with their cancer. Few quantitative studies have assessed the dietary or exercise changes that prostate cancer survivors adopt specifically to help with their cancer. Two studies from the U.S. [49–50] and one from the U.K  found similarly small proportions of survivors currently using diet to help with their cancer (12% to 15%) as was observed in the current study (11.8%). In contrast, another study from the U.S  reported 27.4% and 15.8% of 114 prostate cancer patients had changed their dietary intake and/or physical activity within the previous 12 months, respec- tively, to help cope with the cancer or reduce the risk of spread (with changes assessed up to 24 months after diagnosis in 1997 or 1998). Although the estimates from this U.S. study were based on only 114 prostate cancer patients, they are significantly higher than the correspond- ing 13.5% and 10.2% of survivors in the current study who had ‘ever’ made dietary and exer- cise changes for prostate cancer. The study from the U.S. also reported the specific changes in diet and exercise adopted by their cohort and patient factors associated with such changes, but PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 10 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors Fig 1. Relative proportion (RR) of current use of a) diet and b) exercise for prostate cancer and/or its treatments’ side effects per standard deviation increase in psychological or HRQOL domain for Australian long-term prostate cancer survivors. Adjusted for age, education, socio-economic status of residence area, place of residence, health insurance, employment status, marital status, participation in a support group, country of birth, cancer severity at diagnosis and treatments used since diagnosis. https://doi.org/10.1371/journal.pone.0223407.g001 PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 11 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors these results were not reported specifically for prostate cancer survivors (as the cohort also included breast and colon cancer survivors). In a previous publication, we reported the use of CAMs for prostate cancer by this cohort of 996 long-term survivors . Dietary and exercise modifications and the use of CAMs are similar in that they are activities that many prostate cancer survivors adopt with an aim of improving their cancer and/or treatment related outcomes. These activities differ importantly, however, in that current evidence suggests that prostate cancer survivors might benefit from dietary and exercise modifications, but there is no such evidence supporting the use of CAMs (and some CAMs commonly used for prostate cancer, such as vitamin E , have been linked to harmful outcomes). In our cohort, the prevalences of current CAM use  and current use of diet, exercise or both for prostate cancer were similar (16.9% versus 15.9%), and exactly half of the 158 survivors currently using diet, exercise or both for their cancer were also using CAMs concurrently for their cancer. Similar psychological factors appear to play a role in sur- vivors’ use of CAMs and use of diet for prostate cancer, with both behaviours being related to a fear of cancer recurrence but also seemingly providing men with an increased sense of con- trol over their cancer . Given the high degree of overlapping use of diet, exercise and CAMs for prostate cancer and the presence of common psychological motivators, it may be that survivors who seek advice on CAMs for prostate cancer are likely to be amenable to advice on diet and exercise for prostate cancer. This study has several limitations. First, potential interactions between the factors associ- ated with the use of diet and exercise for prostate cancer were not examined due to insufficient statistical power. Second, a potentially important source of bias is the non-response of 39% of surviving PCOS participants to the 10-year questionnaire. Somewhat reassuringly, however, is the fact that other than a higher proportion of non-respondents being aged 75 years and over, respondents and non-respondents had similar demographic and clinical characteristics [S5 Table]. Moreover, the inclusion of the 10-year non-respondents through multiple imputation made little difference to the original estimates (S2–S4 Tables, S2 and S3 Figs) or to our overall conclusions. Third, because changes in diet and exercise were based on men’s recall measured at one time-point rather than from measurements taken before and after prostate cancer diag- nosis, the observed associations cannot be interpreted as causal. Fourth, self-report of having “ever” made changes to diet or exercise for prostate cancer is vulnerable to recall error as men might struggle to remember changes over the 10-year post-diagnosis period. However, self- report of “current” diet or exercise use for prostate cancer would not be vulnerable to the same recall error. Conclusion In this cohort of long-term prostate cancer survivors, to help with their prostate cancer only one in seven prostate cancer survivors had ever made changes to their diet and only one in ten had ever made changes to the exercise they do. Moreover, one in six prostate cancer survivors were currently using diet, exercise or both for their prostate cancer and a similar proportion were currently using CAMs for the same reason. These findings suggest prostate cancer patients may benefit from counselling on the scientific evidence supporting healthy eating and regular exercise and the absence of evidence supporting the use of CAMs. A key challenge, however, is how to motivate men to modify their lifestyles and then maintain these modifica- tions over the course of their (often long) survivorship. Finally, the updating of prostate cancer survivorship guidelines that reference the latest evidence regarding the benefit of diet and exer- cise for health and wellbeing should be considered a priority in setting the agenda on prostate cancer survivorship. PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 12 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors Supporting information S1 Table. Reasons for—And sources of information on—Current use of diet and exercise for prostate cancer and/or its treatment side effects. (DOCX) S2 Table. Estimated prevalences of current diet and exercise changes with and without multiple imputation of missing data for surviving participants who completed the baseline but not the 10-year questionnaire, and for participants who completed the 10-year ques- tionnaire but had missing data for one or more variables. (DOCX) S3 Table. Estimated adjusted relative proportions (RRs) for associations between current diet/exercise changes and socio-demographic/clinical characteristics with and without multiple imputation of missing data for surviving participants who completed the baseline but not the 10-year questionnaire, and for participants who completed the 10-year ques- tionnaire but had missing data for one or more variables. (DOCX) S4 Table. Comparability of estimated adjusted relative proportions (RRs) corresponding to associations between current diet/exercise changes and other clinical characteristics with and without multiple imputation of missing data for the 638 living participants who completed baseline but not 10-year survey, and for participants who did complete the 10-year questionnaire but had missing data for one or more variables. (DOCX) S5 Table. Demographic and clinical characteristics of PCOS men invited to participate in the 10-year questionnaire; respondents versus non-respondents. (DOCX) S1 Fig. Flow diagram showing patients’ participation and follow-up. (DOCX) S2 Fig. Estimated adjusted relative proportions (RRs) for associations between current diet changes and psychological/HRQOL measures with and without multiple imputation of missing data for surviving participants who completed the baseline but not the 10-year questionnaire, and for participants who completed the 10-year questionnaire but had missing data for one or more variables. (DOCX) S3 Fig. Estimated adjusted relative proportions (RRs) for associations between current exercise changes and psychological/HRQOL measures with and without multiple imputa- tion of missing data for surviving participants who completed the baseline but not 10-year questionnaire, and for participants who completed the 10-year questionnaire but had missing data for one or more variables. (DOCX) Acknowledgments We wish to acknowledge the contributions of Carole Pinnock who provided valuable input into the design of the study and analyses of the results, and Maria Albania, who as a research assistant, played a major role in the processes of recruitment, data collection and data entry. PLOS ONE | https://doi.org/10.1371/journal.pone.0223407 October 3, 2019 13 / 17 Factors associated with the use of diet and exercise for prostate cancer by long-term survivors We would also like to thank Olivia Aitkin, Rose Bollard, Alexandra Christian, Brianna Crocker, Peter Gilmore, Richard Hodgkinson, Erica Hodgkinson, Ashoor Khan, Dong Feng Li, Irena Nagorskaia, Caitlin Van der Walt and Lucy Willocquet for their help with data entry, editing and checking. Finally, we would like to thank all the men who participated and made this study possible. Author Contributions Conceptualization: Suzanne Hughes, David P. Smith, Suzanne Chambers, Annette Moxey, Dianne L. O’Connell. 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