Can Exercise Adaptations Be Maintained in Men with Prostate Cancer Following Supervised Programmes? Implications to the COVID-19 Landscape of Urology and Clinical Exercise.

In this brief correspondence, we evaluate the potential impact of pivoting from face-to-face supervised to unsupervised home-based exercise programmes to contextualise the coronavirus disease 2019 (COVID-19) pandemic in prostate cancer patients. A meta-analysis was undertaken in fatigue, quality of life, and lean and fat mass outcomes in the four studies included. Our analysis indicates that unsupervised home-based exercise maintains patient-reported outcomes, except for fat mass. In summary, changing to unsupervised exercise is unlikely to provide further benefits on patient-reported and body composition outcomes, but may help maintain initial gains during physical distancing restrictions. PATIENT SUMMARY: We discuss the potential impacts of transitioning from face-to-face supervised to unsupervised home-based exercise programmes in prostate cancer patients during the coronavirus disease 2019 (COVID-19) pandemic. Our analysis suggests that patients are likely to maintain patient-reported and body composition benefits from current nonsupervised programmes; however, evolution of exercise delivery to prostate cancer patients is required to continue health and fitness improvement in this group.

Efficacy of a weight loss program prior to robot assisted radical prostatectomy in overweight and obese men with prostate cancer.

BACKGROUND: Obesity in prostate cancer patients is associated with poor prostate-cancer specific outcomes. Exercise and nutrition can reduce fat mass; however, few studies have explored this as a combined pre-surgical intervention in clinical practice. PURPOSE: This study examined the efficacy of a weight loss program for altering body composition in prostate cancer patients prior to robot assisted radical prostatectomy (RARP). METHODS: A retrospective analysis of 43 overweight and obese prostate cancer patients, aged 47-80 years, who completed a very low-calorie diet (~3000-4000 kJ) combined with moderate-intensity exercise (90 min/day) prior to RARP. Whole body and regional fat mass (FM) and lean mass (LM) were assessed by dual-energy x-ray absorptiometry pre- and post-program. Body weight, waist circumference, and blood pressure were assessed weekly, with surgery-related adverse effects recorded at time of surgery and follow-up appointments. RESULTS: With a median of 29 days (IQR: 24-35days) on the program, patients significantly (p < 0.001) reduced weight (-7.3 ± 2.9 kg), FM (-5.0 ± 2.6 kg), percent body fat (-3.1 ± 2.5%), trunk FM (-3.4 ± 1.8 kg), LM (-2.4 ± 1.8 kg), and appendicular LM (-1.2 ± 1.0 kg). Lower weight, FM, percent FM, trunk FM, and visceral FM were associated with less surgery-related adverse effects (rs = 0.335 to 0.468, p < 0.010). Systolic and diastolic blood pressure were reduced (p < 0.001) by 15 ± 22 and 8 ± 10 mmHg, respectively over the weight loss intervention. CONCLUSION: Undertaking a combined low-calorie diet and exercise program for weight loss in preparation for RARP resulted in substantial reductions in FM, with improvements in blood pressure, that may benefit surgical outcomes.

Radiation Dose Escalation or Longer Androgen Suppression to Prevent Distant Progression in Men With Locally Advanced Prostate Cancer: 10-Year Data From the TROG 03.04 RADAR Trial.

PURPOSE: To clarify the relative effects of duration of androgen suppression (AS) and radiation dose escalation (RDE) on distant progression (DP) in men with locally advanced prostate cancer. METHODS AND MATERIALS: Participants with locally advanced prostate cancer in the TROG 03.04 RADAR trial were randomized to 6 or 18 months AS ± 18 months zoledronic acid (Z). The trial incorporated a RDE program by stratification at randomization and dosing options were 66, 70, or 74 Gy external beam radiation therapy (EBRT), or 46 Gy EBRT plus high-dose-rate brachytherapy boost (HDRB). The primary endpoint for this study was distant progression (DP). Secondary endpoints included local progression, bone progression, prostate cancer-specific mortality and all-cause mortality. Effect estimates for AS duration and RDE were derived using Fine and Gray competing risk models adjusting for use of Z, age, tumor stage, Gleason grade group, prostate-specific antigen, and treatment center. Cumulative incidence at 10 years was estimated for each RDE group. RESULTS: A total of 1051 out of 1071 randomized subjects were eligible for inclusion in this analysis. Compared with 6 months AS, 18 months AS significantly reduced DP independently of radiation dose (subhazard ratio 0.70; 95% confidence interval [CI], 0.56-0.87; P = .002). No statistically significant interaction between effect of AS duration and RT dose was observed (Wald test P = .76). In subgroup analyses, DP was significantly reduced by the longer duration of AS in the 70 Gy and HDRB groups but not in the 66 Gy and 74 Gy. Compared with 70 Gy, HDRB significantly reduced DP (subhazard ratio 0.68 [95% CI, 0.57-0.80]; P < .0001) independently of AS duration. At 10 years, adjusted cumulative incidences were 26.1% (95% CI, 18.9%-33.2%), 26.7% (22.9%-30.6%), 24.9% (20.0%-29.8%) and 19.7% (15.5%-23.8%) for DPs in the respective radiation dose groups. CONCLUSIONS: Compared with 6 months AS, 18 months AS reduced DP independently of radiation dose. Men treated with HDRB gained a significant benefit from a longer duration of AS. Evidence of improved oncologic outcomes for HDRB compared with dose-escalated EBRT needs to be confirmed in a randomized trial.

The Prevalence and Determinants of Vitamin D Status in Community-Dwelling Older Adults: Results from the English Longitudinal Study of Ageing (ELSA).

Vitamin D deficiency is often associated with adverse health outcomes in older adults. The circulating 25-hydroxyvitamin D (25(OH)D) status predominately relies on UV exposure. However, the extent of which northerly latitude exasperates deficiency is less explored in ageing. We aimed to investigate vitamin D deficiency in community-dwelling, older adults, residing at latitudes 50-55° north. This study was comprised of 6004 adults, aged >50 years from wave 6 (2012-2013) of the English Longitudinal Study of Ageing (ELSA). Deficiency was categorised by two criteria: Institute of Medicine (IOM) (<30 nmol/L) and Endocrine Society (ES) (<50 nmol/L). The overall prevalence of Institute of Medicine (IOM) and Endocrine Society (ES) definitions of deficiency were 26.4% and 58.7%, respectively. Females (odds ratio (OR) 1.23; CI: 1.04-1.44), those aged 80+ (OR: 1.42; CI: 1.01-1.93), smoking (OR: 1.88; CI: 1.51-2.34); of non-white ethnicity (OR: 3.8; CI:2.39-6.05); being obese (OR: 1.32; CI:1.09-1.58), and of poor self-reported health (OR:1.99; CI:1.33, 2.96), were more likely to be vitamin D deficient (by IOM). Residents in the south of England had a reduced risk of deficiency (OR: 0.78; CI:0.64-0.95), even after adjustment for socioeconomic and traditional predictors (obesity, age, lifestyle, etc.) of vitamin D status. Other factors, such as being retired, having a normal BMI, engaging in regular vigorous physical activity, vitamin D supplement use, sun travel, and summer season were also significantly positive correlates of deficiency. Similar results were observed for the ES cut-off definition. Importantly, more than half of adults aged >50 years had 25(OH)D concentrations <50 nmol/L. These findings demonstrate that low vitamin D status is highly prevalent in older English adults and the crucial importance of public health strategies throughout midlife and older age to achieve optimal vitamin D status.

The Prevalence of Vitamin D Deficiency and the Determinants of 25(OH)D Concentration in Older Irish Adults: Data From The Irish Longitudinal Study on Ageing (TILDA).

Background: Few data are available examining the determinants of vitamin D status exclusively in older adults. We aimed to investigate the prevalence and determinants of vitamin D deficiency in a representative sample of the older Irish population (aged 50-98 years). Methods: The concentration of 25-hydroxyvitamin D (25(OH)D) was measured in 5,356 community-dwelling older Irish adults from The Irish Longitudinal Study on Ageing (TILDA). Detailed demographic, geographic, lifestyle, and socioeconomic factors were assessed by questionnaire. Proportions of deficiency prevalence were generated by season sampled. Linear regression was used to investigate the association between 25(OH)D concentration and reported risk factors. Results: The prevalence of deficiency (25(OH)D < 30 nmol/L) was 13.1% (95% CI: 12.1-14.2). Deficiency status was more prevalent in nonsupplement users, in winter, in smokers, in obese adults, the physically inactive, those living alone, and in the oldest old (>80 years). The main predictors (p < .05) of 25(OH)D concentration were supplement use (coefficient nmol/L: 27.2 [95% CI: 15.3-39.2]), smoking (-8.9 [-12.6--5.2]), summer season (5.9 [2.7-9.1]), and obesity (-4.0 [-6.3--1.7]). Conclusion: Vitamin D deficiency is common among older Irish adults. These data indicate the need for targeted strategies within sections of the older population to improve vitamin D status.

The Australian laparoscopic radical prostatectomy learning curve.

BACKGROUND: International estimates of the laparoscopic radical prostatectomy (LRP) learning curve extend to as many as 1000 cases, but is unknown for Fellowship-trained Australian surgeons. METHODS: Prospectively collected data from nine Australian surgeons who performed 2943 consecutive LRP cases was retrospectively reviewed. Their combined initial 100 cases (F100, n = 900) were compared to their second 100 cases (S100, n = 782) with two of nine surgeons completing fewer than 200 cases. RESULTS: The mean age (61.1 versus 61.1 years) and prostate specific antigen (7.4 versus 7.8 ng/mL) were similar between F100 and S100. D'Amico's high-, intermediate- and low-risk cases were 15, 59 and 26% for the F100 versus 20, 59 and 21% for the S100, respectively. Blood transfusions (2.4 versus 0.8%), mean blood loss (413 versus 378 mL), mean operating time (193 versus 163 min) and length of stay (2.7 versus 2.4 days) were all lower in the S100. Histopathology was organ confined (pT2) in 76% of F100 and 71% of S100. Positive surgical margin (PSM) rate was 18.4% in F100 versus 17.5% in the S100 (P = 0.62). F100 and S100 PSM rates by pathological stage were similar with pT2 PSM 12.2 versus 9.5% (P = 0.13), pT3a PSM 34.8 versus 40.5% (P = 0.29) and pT3b PSM 52.9 versus 36.4% (P = 0.14). CONCLUSION: There was no significant improvement in PSM rate between F100 and S100 cases. Perioperative outcomes were acceptable in F100 and further improved with experience in S100. Mentoring can minimize the LRP learning curve, and it remains a valid minimally invasive surgical treatment for prostate cancer in Australia even in early practice.

The Australian laparoscopic non robotic radical prostatectomy experience - analysis of 2943 cases (USANZ supplement).

OBJECTIVES: To analyse the Australian experience of high-volume Fellowship-trained Laparoscopic Radical Prostatectomy (LRP) surgeons. MATERIALS AND METHODS: 2943 LRP cases were performed by nine Australian surgeons. The inclusion criteria were a prospectively collected database with a minimum of 100 consecutive LRP cases. The surgeons' LRP experience commenced at various times from July 2003 to September 2009. Data were analysed for demographic, peri-operative, oncological and functional outcomes. RESULTS: The mean age of patients were 61.5 years and mean preoperative PSA 7.4 ng/ml. Mean operating time was 168 minutes with conversion to open surgery in 0.5% and a blood transfusion rate of 1.1%. Overall mean length of stay was 2.5 days. 73.6% of pathological specimens were pT2 and 86.3% had Gleason Score >7. Overall positive surgical margins (PSM) occurred in 15.9% with pT2 PSM 9.8%, pT3a PSM 30.8% and pT3b PSM 39.2%. Mean urinary continence at 12 months was 91.4% (data available from five surgeons). Mean 12 months potency after bilateral nerve spare was 47.2% (data available from four surgeons). Biochemical recurrence occurred in 10.6% (mean follow up 17 months). CONCLUSION: The Australian experience of Fellowship trained surgeons performing LRP demonstrates favourable peri-operative, oncological and functional outcomes in comparison to published data for open, laparoscopic and robotic assisted radical prostatectomy. In our Australian centres, LRP remains an acceptable minimally invasive surgical treatment for prostate cancer despite the increasing use of robotic assisted surgery.

Ten-year outcomes using low dose rate brachytherapy for localised prostate cancer: An update to the first Australian experience.

INTRODUCTION: To report long-term prostate-specific antigen (PSA) and toxicity outcomes for patients with localised prostate cancer treated with Iodine-125 permanent implantation at a single Australian centre. METHODS: Between September 1994 and November 2007, 207 patients at Sir Charles Gairdner Hospital with localised prostate cancer were consecutively treated with Iodine-125 permanent interstitial implantation. Post-therapy assessment was performed three times a month and included clinical review and biochemical (PSA) evaluation. PSA progression was evaluated using the Phoenix (nadir + 2.0) definition. Treatment-related morbidity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 guidelines. The rate of biochemical failure was calculated by Kaplan-Meier plots. Univariate and multivariate analyses were performed to evaluate outcomes by pre-treatment clinical prognostic factors and radiation dosimetry. RESULTS: Median follow-up was 7.8 years. The 10-year biochemical disease-free survival (bDFS) for the entire cohort was 89%. Ten-year bDFS estimates by pre-treatment risk group were 96% for low-risk, 83% for intermediate-risk and 50% for high-risk disease. On multivariate analysis, pre-treatment PSA was an independent predictor of bDFS. D90 dose did not show a statistically significant effect on bDFS. The peak incidences of late grade 3 or higher urinary and rectal toxicities were 10.7% and 1.1% respectively. CONCLUSION: Excellent long-term biochemical control was demonstrated with Iodine-125 permanent interstitial implantation in appropriately selected patients with prostate cancer. The results of our single centre experience are comparable with those of other single institutions.

Enhancing active surveillance of prostate cancer: the potential of exercise medicine.

Active surveillance (AS) is a strategy for the management of patients with low-risk, localized prostate cancer, in which men undergo regular monitoring of serum PSA levels and tumour characteristics, using multiparametric MRI and repeat biopsy sampling, to identify signs of disease progression. This strategy reduces overtreatment of clinically insignificant disease while also preserving opportunities for curative therapy in patients whose disease progresses. Preliminary studies of lifestyle interventions involving basic exercise advice have indicated that exercise reduces the numbers of patients undergoing active treatment, as well as modulating the biological processes involved in tumour progression. Therefore, preliminary evidence suggests that lifestyle and/or exercise interventions might have therapeutic potential in this growing population of men with prostate cancer. However, several important issues remain unclear: the exact value of different types of lifestyle and exercise medicine interventions during AS; the biological mechanisms of exercise in delaying disease progression; and the influence of the anxieties and distress created by having a diagnosis of cancer without then receiving active treatment. Future studies are required to confirm and expand these findings and determine the relative contributions of each lifestyle component to specific end points and patient outcomes during AS.

Laparoscopic donor nephrectomy.

BACKGROUND: Kidney transplantation is a definitive treatment of end-stage renal disease. Laparoscopic donor nephrectomy (LDN) has been widely accepted around the world since its introduction in 1995 as a minimum invasive procedure. We report our clinical experience of 141 consecutive LDNs performed in two tertiary hospitals in Western Australia. METHODS: From December 2000 (Royal Perth Hospital) and January 2005 (Sir Charles Gairdner Hospital) to January 2009, 141 LDNs were performed in two tertiary hospitals by four urologists. All donors underwent rigorous work-up prior to surgery. Donor age ranged from 23 years to 81 years (49.85 ± 11.30 years). The male to female ratio was 1 to 1.3. Donor body mass index (BMI) was 26.77 ± 4.31, and glomerular filtration rate was 96.25 ± 12.33 mL/min/1.73 sqm. The laparoscopic technique was transperitoneal approach exclusively. RESULTS: All LDNs were performed successfully without hand assistance. The warm ischaemic time ranged from 3 to 11 min. The hospital stay was 4.16 ± 1.30 days. The overall complication rate was 17.0%, with three major complications (2.1%): a splenetic infarction, a chylous ascites and a pulmonary embolism occurred. Donors' demographic data (age, sex, BMI, side of surgery) did not show a statistically significant association with surgical complications. CONCLUSIONS: Transperitoneal laparoscopic live donor nephrectomy is a safe and effective procedure. Combined use of vascular stapler and Hem-o-Lok is very important for management of the renal artery stump. It is our current practice to administer anticoagulants during and post-surgery for at least 2 weeks.

Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer.

OBJECTIVE: To assess the effects of androgen deprivation therapy (ADT) on whole-body and regional muscle, fat and bone mass in men with prostate cancer without metastatic bone disease. PATIENTS AND METHODS: Seventy-two men aged 44-88 years underwent spine, hip and whole-body dual-energy X-ray absorptiometry scans at baseline and after 36 weeks of ADT. The change in whole-body and regional lean mass (LM), fat mass (FM), and bone mineral content and density (BMD) were determined. In addition, the prostate specific antigen (PSA), serum testosterone and haemoglobin levels were measured, and the level of physical activity and fatigue assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-30. RESULTS: The upper limb, lower limb, trunk and whole-body LM decreased by a mean (sem) of 5.6 (0.6)%, 3.7 (0.5)%, 1.4 (0.5)% and 2.4 (0.4)% (P < 0.01), respectively, while FM increased by 20.7 (3.3)%, 18.7 (2.7)%, 12.0 (2.5)% and 13.8 (2.3)% (P < 0.001). Hip, spine, whole-body and upper limb BMD decreased by 1.9 [corrected] (0.3)% [corrected], 3.3 [corrected] (0.4)%, 1.6 [corrected] (0.3)% and 1.3 (0.3%) (P < 0.001), but not lower limb BMD. Serum testosterone, PSA and haemoglobin levels decreased by 93.3 (0.4)%, 98.2 (0.5)%, and 8.8 (0.9)% (P < 0.001), respectively. In addition, physical activity levels decreased and levels of fatigue increased. CONCLUSION: After 36 weeks of ADT there was a significant decrease in whole-body and regional LM and bone mass, while whole-body and regional FM increased in older men with prostate cancer. Strategies to counteract changes in soft tissue and bone mass during ADT should be formulated to minimize the risk of sarcopenia, osteoporosis and obesity.

Propionibacterium acnes associated with inflammation in radical prostatectomy specimens: a possible link to cancer evolution?

PURPOSE: Inflammation is commonly observed in the prostate gland and has been implicated in the development of prostate cancer. The etiology of prostatic inflammation is unknown. However, the involvement of a carcinogenic infectious agent has been suggested. MATERIALS AND METHODS: Prostatic tissue from 34 consecutive patients with prostate cancer was cultured to detect the presence of bacterial agents. Prostatic inflammation was assessed by histological examination of wholemount tissue sections. RESULTS: The predominant microorganism detected was Propionibacterium acnes, found in 35% of prostate samples. A significantly higher degree of prostatic inflammation was observed in cases culture positive for P. acnes (p =0.007). P. acnes was separated into 3 groups based on cell surface properties, phenotype and genetic grouping. All skin control isolates were classified as group 1 whereas most prostatic isolates were classified as groups 2 and 3. CONCLUSIONS: P. acnes has been isolated from prostatic tissues in men who underwent radical prostatectomy for localized cancer and has been shown to be positively associated with prostatic inflammation. This inflammation may then be linked to the evolution of carcinoma. Furthermore, organisms infecting these patients with prostate cancer differ genetically and phenotypically from the commonly identified cutaneous P. acnes isolates, suggesting that specific subtypes may be involved in development of prostatic inflammation.