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1.
Responsiveness to Resistance-Based Multimodal Exercise Among Men With Prostate Cancer Receiving Androgen Deprivation Therapy.
Taaffe, DR, Newton, RU, Spry, N, Joseph, DJ, Galvão, DA
Journal of the National Comprehensive Cancer Network : JNCCN. 2019;(10):1211-1220
Abstract
BACKGROUND Androgen deprivation therapy (ADT) in the management of prostate cancer (PCa) results in an array of adverse effects, and exercise is one strategy to counter treatment-related musculoskeletal toxicities. This study assessed the prevalence of exercise responsiveness in men with PCa undergoing ADT in terms of body composition, muscle strength, and physical function. METHODS Prospective analyses were performed in 152 men (aged 43-90 years) with PCa receiving ADT who were engaged in resistance exercise combined with aerobic or impact training for 3 to 6 months. Whole-body lean mass and fat mass (FM), trunk FM, and appendicular skeletal muscle were assessed with dual x-ray absorptiometry; upper and lower body muscle strength were assessed with the one-repetition maximum; and physical function was assessed with a battery of tests (6-m usual, fast, and backward walk; 400-m walk; repeated chair rise; stair climb). RESULTS Significant improvements were seen (P<.01) in lean mass (0.4±1.4 kg [range, -2.8 to +4.1 kg]), appendicular skeletal muscle (0.2±0.8 kg [range, -1.9 to +1.9 kg]), and all measures of muscle strength (chest press, 2.9±5.8 kg [range, -12.5 to +37.5 kg]; leg press, 29.2±27.6 kg [range, -50.0 to +140.0 kg]) and physical function (from -0.1±0.5 s [range, +1.3 to -2.1 s] for the 6-m walk; to -8.6±15.2 s [range, +25.2 to -69.7 s] for the 400-m walk). An increase in FM was also noted (0.6±1.8 kg [range, -3.6 to +7.3 kg]; P<.01). A total of 21 men did not exhibit a favorable response in at least one body composition component, 10 did not experience improved muscle strength, and 2 did not have improved physical function. However, all patients responded in at least one of the areas, and 120 (79%) favorably responded in all 3 areas. CONCLUSIONS Despite considerable heterogeneity, most men with PCa receiving ADT responded to resistance-based multimodal exercise, and therefore our findings indicate that this form of exercise can be confidently prescribed to produce beneficial effects during active treatment.
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Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study.
Adams, CD, Richmond, R, Ferreira, DLS, Spiller, W, Tan, V, Zheng, J, Würtz, P, Donovan, J, Hamdy, F, Neal, D, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2019;(1):208-216
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Abstract
BACKGROUND Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR). METHODS The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. RESULTS Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. CONCLUSIONS We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. IMPACT The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
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A lifestyle intervention of weight loss via a low-carbohydrate diet plus walking to reduce metabolic disturbances caused by androgen deprivation therapy among prostate cancer patients: carbohydrate and prostate study 1 (CAPS1) randomized controlled trial.
Freedland, SJ, Howard, L, Allen, J, Smith, J, Stout, J, Aronson, W, Inman, BA, Armstrong, AJ, George, D, Westman, E, et al
Prostate cancer and prostatic diseases. 2019;(3):428-437
Abstract
PURPOSE The objective of this study was to test a low-carbohydrate diet (LCD) plus walking to reduce androgen deprivation therapy (ADT)-induced metabolic disturbances. MATERIALS AND METHODS This randomized multi-center trial of prostate cancer (PCa) patients initiating ADT was designed to compare an LCD (≤20g carbohydrate/day) plus walking (≥30 min for ≥5 days/week) intervention vs. control advised to maintain usual diet and exercise patterns. Primary outcome was change in insulin resistance by homeostatic model assessment at 6 months. To detect 20% reduction in insulin resistance, 100 men were required. The study was stopped early after randomizing 42 men due to slow accrual. Secondary outcomes included weight, body composition, lipids, and prostate-specific antigen (PSA). Changes from baseline were compared between arms using rank-sum tests. RESULTS At 6 months, LCD/walking reduced insulin resistance by 4% vs. 36% increase in control (p = 0.13). At 3 months, vs. control, LCD/walking arm significantly lost weight (7.8kg; p<0.001), improved insulin resistance (↑36%; p = 0.015), hemoglobin A1c (↓3.3%; p = 0.01), high-density lipoprotein (HDL) (↑13%; p = 0.004), and triglyceride (↓37%; p = 0.036). At 6 months, weight loss (10.6kg; p<0.001) and HDL (↑27%; p = 0.003) remained significant. LCD/walking preserved total body bone mineral count (p = 0.025), reduced fat mass (p = 0.002), lean mass (p = 0.036), and percent body fat (p = 0.004). There were no differences in PSA. Limitations include the effect of LCD, weight loss vs. walking instruction are indistinguishable, and small sample size. CONCLUSIONS In an underpowered study, LCD/walking did not improve insulin sensitivity at 6 months. Given most secondary outcomes were improved at 3 months with some remaining improved at 6 months and a secondary analysis showed that LCD/walking reduced insulin resistance over the study, supporting future larger studies of LCD/walking intervention to reduce ADT-induced disturbances.
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WATER II (80-150 mL) procedural outcomes.
Desai, M, Bidair, M, Bhojani, N, Trainer, A, Arther, A, Kramolowsky, E, Doumanian, L, Elterman, D, Kaufman, RP, Lingeman, J, et al
BJU international. 2019;(1):106-112
Abstract
OBJECTIVES To present early safety and feasibility data from a multicentre prospective study (WATER II) of aquablation in the treatment of symptomatic men with large-volume benign prostatic hyperplasia (BPH). METHODS Between September and December 2017, 101 men with moderate-to-severe BPH symptoms and prostate volume of 80-150 mL underwent aquablation in a prospective multicentre international clinical trial. Baseline demographics and standardized postoperative management variables were carefully recorded in a central independently monitored database. Surgeons answered analogue scale questionnaires on intra-operative technical factors and postoperative management. Adverse events up to 1 month were adjudicated by an independent clinical events committee. RESULTS The mean (range) prostate volume was 107 (80-150) mL. The mean (range) operating time was 37 (15-97) min and aquablation resection time was 8 (3-15) min. Adequate adenoma resection was achieved with a single pass in 34 patients and with additional passes in 67 patients (mean 1.8 treatment passes), all in a single operating session. Haemostasis was achieved using either a Foley balloon catheter placed in the bladder under traction (n = 98, mean duration 18 h) or direct tamponade using a balloon inflated in the prostate fossa (n = 3, mean duration 15 h). No patient required electrocautery for haemostasis at the time of the primary procedure. The mean length of stay after the procedure was 1.6 days (range same day to 6 days). The Clavien-Dindo grade ≥2 event rate observed at 1 month was 29.7%. Bleeding complications were recorded in 10 patients (9.9%) during the index procedure hospitalization prior to discharge, and included six (5.9%) peri-operative transfusions. CONCLUSIONS Aquablation is feasible and safe in treating men with men with large prostates (80-150 mL). The 6-month efficacy data are being accrued and will be presented in future publications (ClinicalTrials.gov number, NCT03123250).
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Comparison of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and bone scintigraphy in the diagnosis of bone metastases in patients with prostate cancer: a systematic review and meta-analysis.
Zhou, J, Gou, Z, Wu, R, Yuan, Y, Yu, G, Zhao, Y
Skeletal radiology. 2019;(12):1915-1924
Abstract
OBJECTIVE A systematic review and meta-analysis to compare the diagnostic performance of prostate-specific membrane antigen (PSMA)-PET/CT, choline-PET/CT, Sodium Fluoride (NaF) PET/CT, MRI, and bone scintigraphy (BS) in detecting bone metastases in patients with prostate cancer. METHODS We searched PubMed and Embase for articles published between January 1990 and September 2018. Two evaluators independently extracted the sensitivity, specificity, the numbers of true and false positives, and true and false negatives. We calculated the pooled sensitivity, specificity, and 95% confidence intervals (CI) for each method. We calculated the tests' diagnostic odds ratios (DOR); drew the summary receiver operating characteristic (SROC) curves; and obtained the areas under the curves (AUC), Q* values, and 95% CIs. RESULTS The per-patient pooled sensitivities of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and BS were 0.97, 0.87, 0.96, 0.91, and 0.86, respectively. The pooled specificities were 1.00, 0.99, 0.97, 0.96, and 0.95, respectively. The pooled DOR values were 504.16, 673.67, 242.63, and 114.44, respectively. The AUC were 1.00, 0.99, 0.99, 0.98, and 0.95, respectively. The per-lesion pooled sensitivities of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and bone imaging were 0.88, 0.80, 0.97, 0.81 and 0.68, respectively. CONCLUSIONS According to the meta-analysis, PSMA-PET/CT had the highest per-patient sensitivity and specificity in detecting bone metastases with prostate cancer. The sensitivities of NaF-PET/CT and MRI were better than those for choline-PET/CT and BS. The specificity of PSMA-PET/CT was significantly better than BS. Others were similar. For per-lesion, NaF-PET/CT had the highest sensitivity, PSMA-PET/CT had higher sensitivity than choline-PET/CT and MRI, and BS had the lowest sensitivity.
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18F-NaF-PET/CT for the detection of bone metastasis in prostate cancer: a meta-analysis of diagnostic accuracy studies.
Sheikhbahaei, S, Jones, KM, Werner, RA, Salas-Fragomeni, RA, Marcus, CV, Higuchi, T, Rowe, SP, Solnes, LB, Javadi, MS
Annals of nuclear medicine. 2019;(5):351-361
Abstract
PURPOSE This meta-analysis aims to establish the diagnostic performance of 18F-NaF-PET/CT for the detection of bone metastases in prostate cancer patients. The performance of 18F-NaF-PET/CT was compared with other imaging techniques in the same cohort of patients. METHODS A systematic search was performed in PubMed/Medline and EMBASE (last Updated, September 28, 2018). Studies with histopathology confirmation and/or clinical/imaging follow-up as reference standard were eligible for inclusion. RESULTS A total of 14 studies were included. Twelve studies including 507 patients provided per-patient basis information. The pooled sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristics curve (AUC) of 18F-NaF-PET/CT for the detection of bone metastases were 0.98 (95% CI 0.95-0.99), 0.90 (95% CI 0.86-0.93), 123.2 and 0.97, respectively. Seven studies provided the lesion-based accuracy information of 1812 lesions identified on 18F-NaF-PET/CT with the pooled sensitivity, specificity, DOR and AUC of 0.97 (95% CI 0.95-0.98), 0.84 (95% CI 0.81-0.87), 206.8 and 0.97, respectively. The overall diagnostic performance of 18F-NaF-PET/CT is superior to 99mTc-bone scintigraphy (AUC 0.842; P < 0.001; four studies) and 99mTc-SPECT (AUC 0.896; P < 0.001, four studies). Compared to 18F NaF-PET/CT, whole-body MRI with diffusion-weighted imaging (DWI) was shown to have lower sensitivity (0.83, 95% CI 0.68-0.93), with no significant difference in the overall performance (AUC 0.947; P = 0.18, four studies). CONCLUSION 18F-NaF-PET/CT has excellent diagnostic performance in the detection of bone metastases in staging and restaging of high-risk prostate cancer patients. The performance of 18F-NaF-PET/CT is superior to 99mTc bone scintigraphy and SPECT, and comparable to DWI-MRI.
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Nutrition care guidelines for men with prostate cancer undergoing androgen deprivation therapy: do we have enough evidence?
Barnes, KA, Ball, LE, Galvão, DA, Newton, RU, Chambers, SK
Prostate cancer and prostatic diseases. 2019;(2):221-234
Abstract
BACKGROUND To review the evidence available to support clinical practice guidelines for dietary interventions aimed at mitigating the side effects of androgen deprivation therapy (ADT) in men with prostate cancer, and to identify future research priorities. METHODS An analytical model was designed to select and interpret evidence for the effect of dietary interventions on ADT side effects. Key terms identified articles that investigated dietary interventions to mitigate ADT side effects among men treated for prostate cancer. Medline, Embase, Proquest, CINAHL, Cochrane databases, and PubMed were searched from inception through June, 2018. Clinical trial registries were also searched for up-to-date study protocols. Articles were not restricted on design. Methodological quality was assessed using the mixed methods appraisal tool. RESULTS Sixteen articles met inclusion criteria, each with distinct dietary interventions. Twelve studies used interventions that combined diet with physical activity and/or medication and/or counselling. Four articles examined the effect of diet alone on ADT side effects. Of those, three articles measured changes to participants' dietary intake and influence on ADT side effects. One article showed daily caffeinated beverages improved cancer-related fatigue. Two articles showed no impact of isoflavone supplementation on hot flushes, quality of life, body mass index, or blood lipids. Dietary intake and compliance was poorly reported across all studies limiting knowledge of acceptability and feasibility for dietary interventions. Information on the nutrition care practices and views of clinicians treating men for prostate cancer is limited. No articles measured the impact of diet on long-term ADT side effects. Methodological quality of included papers ranged from weak to strong. CONCLUSIONS Current evidence for dietary interventions to mitigate ADT side effects is limited. Further investigations are warranted to explore the impact of changes in dietary intake on ADT side effects before practice guidelines can be considered.
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Lost in translation: lessons learned from the "demise" of MRSI of the prostate.
Westphalen, AC
Abdominal radiology (New York). 2019;(9):3185-3187
Abstract
At times, technologies fail for reasons other than an inability to deliver on their promises. The iconic Blackberry, for example, was once coined "Research in Motion", sold tens of millions of units, and then "disappeared" from the market because it did not accompany the new trends in design. Promising technologies may also "disappear" in the medical field. What follows is the tale of the rise and fall of proton magnetic resonance spectroscopic imaging (1H MRSI) of the prostate.
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Exercise Mode Specificity for Preserving Spine and Hip Bone Mineral Density in Prostate Cancer Patients.
Newton, RU, Galvão, DA, Spry, N, Joseph, D, Chambers, SK, Gardiner, RA, Wall, BA, Bolam, KA, Taaffe, DR
Medicine and science in sports and exercise. 2019;(4):607-614
Abstract
PURPOSE Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with an array of adverse effects, including reduced bone mineral density (BMD) predisposing patients to increased fracture risk. Our purpose was to examine the effects of targeted exercise modes on BMD in men with PCa undergoing ADT. METHODS Between 2009 and 2012, 154 PCa patients 43-90 yr old on ADT were randomized to exercise targeting the musculoskeletal system (impact loading + resistance training [ImpRes], n = 57) supervised for 12 months, cardiovascular and muscular systems (aerobic + resistance training, n = 50) supervised for 6 months followed by a 6-month home-based program, or delayed aerobic exercise (DelAer, n = 47) received exercise information for 6 months followed by 6 months of supervised aerobic exercise (stationary cycling). End points were lumbar spine, hip and whole-body BMD measured by dual-energy x-ray absorptiometry with secondary end points of lean and fat mass, appendicular skeletal muscle mass, and neuromuscular strength. ANOVA was used to compare the exercise groups with DelAer at 6 and 12 months. RESULTS There was a between-group difference in BMD for ImpRes and DelAer at the spine (6 months, P = 0.039; 12 months, P = 0.035) and femoral neck (6 months, P = 0.050), with decline attenuated in ImpRes (~-1.0% vs ~-2.0%). Compared with DelAer, ImpRes increased appendicular skeletal muscle at 6 months (0.3 kg, P = 0.045) and improved muscle strength at 6 and 12 months (P ≤ 0.012) by 9%-34%. A limitation was inclusion of well-functioning patients. CONCLUSION Combined impact loading and resistance exercise attenuates bone loss at the spine and enhances overall musculoskeletal function in PCa patients undergoing ADT.
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A self-help diet and physical activity intervention with dietetic support for weight management in men treated for prostate cancer: pilot study of the Prostate Cancer Weight Management (PRO-MAN) randomised controlled trial.
Mohamad, H, Ntessalen, M, Craig, LCA, Clark, J, Fielding, S, N'Dow, J, Heys, SD, McNeill, G
The British journal of nutrition. 2019;(5):592-600
Abstract
Overweight and obesity may increase risk of disease progression in men with prostate cancer, but there have been few studies of weight loss interventions in this patient group. In this study overweight or obese men treated for prostate cancer were randomised to a self-help diet and activity intervention with telephone-based dietitian support or a wait-list mini-intervention group. The intervention group had an initial group meeting, a supporting letter from their urological consultant, three telephone dietitian consultations at 4-week intervals, a pedometer and access to web-based diet and physical activity resources. At 12 weeks, men in both groups were given digital scales for providing follow-up weight measurements, and the wait-list group received a mini-intervention of the supporting letter, a pedometer and access to the web-based resources. Sixty-two men were randomised; fifty-four completed baseline and 12-week measurements, and fifty-one and twenty-seven provided measurements at 6 and 12 months, respectively. In a repeated-measures model, mean difference in weight change between groups (wait-list mini-intervention minus intervention) at 12 weeks was -2·13 (95 % CI -3·44, -0·82) kg (P = 0·002). At 12 months the corresponding value was -2·43 (95 % CI -4·50, -0·37) kg (P = 0·022). Mean difference in global quality of life score change between groups at 12 weeks was 12·3 (95 % CI 4·93, 19·7) (P = 0·002); at 12 months there were no significant differences between groups. Results suggest the potential of self-help diet and physical activity intervention with trained support for modest but sustained weight loss in this patient group.