Onset of androgen deprivation therapy leads to rapid deterioration of body composition, physical performance, cardiometabolic health and quality-of-life in prostate cancer patients.

OBJECTIVES: To assess the adverse impact of the first 5 months of androgen deprivation therapy on body composition, physical performance, cardiometabolic health and health-related quality-of-life in prostate cancer patients. MATERIALS AND METHODS: Thirty-four prostate cancer patients (70 ± 7 years) were assessed shortly after initiation of androgen deprivation therapy and again 5 months thereafter. Measurements consisted of whole-body dual-energy x-ray absorptiometry (body composition), computed tomography scanning of the upper leg (muscle mass), one-repetition maximum leg press (muscle strength), cardiopulmonary exercise testing (aerobic capacity), blood draws (metabolic parameters), accelerometry (habitual physical activity) and questionnaires (health-related quality-of-life). Data were analyzed with Student's paired t-tests. RESULTS: Over time, whole-body fat mass (from 26.2 ± 7.7 to 28.4 ± 8.3 kg, p < 0.001) and fasting insulin (from 9.5 ± 5.8 to 11.3 ± 6.9 mU/L, p < 0.001) increased. Declines were observed for quadriceps cross-sectional area (from 66.3 ± 9.1 to 65.0 ± 8.5 cm2, p < 0.01), one-repetition maximum leg press (from 107 ± 27 to 100 ± 27 kg, p < 0.01), peak oxygen uptake (from 23.2 ± 3.7 to 20.3 ± 3.4 mL/min/kg body weight, p < 0.001), step count (from 7,048 ± 2,277 to 5,842 ± 1,749 steps/day, p < 0.01) and health-related quality-of-life (from 84.6 ± 13.5 to 77.0 ± 14.6, p < 0.001). CONCLUSIONS: Androgen deprivation therapy induces adverse changes in body composition, muscle strength, cardiometabolic health and health-related quality-of-life already within 5 months after the start of treatment, possibly largely contributed by diminished habitual physical activity. Prostate cancer patients should, therefore, be stimulated to increase their habitual physical activity immediately after initiation of androgen deprivation therapy, to limit adverse side-effects and to improve health-related quality-of-life.

Resistance Exercise Training Increases Muscle Mass and Strength in Prostate Cancer Patients on Androgen Deprivation Therapy.

PURPOSE: This study aimed to assess the effects of 20 wk resistance exercise training with or without protein supplementation on body composition, muscle mass, muscle strength, physical performance, and aerobic capacity in prostate cancer patients receiving androgen deprivation therapy (ADT). METHODS: Sixty prostate cancer patients receiving ADT were randomly assigned to perform 20 wk of resistance exercise training with supplementation of 31 g whey protein (EX + PRO, n = 30) or placebo (EX + PLA, n = 30), consumed immediately after exercise and every night before sleep. A separate control group (CON, n = 36) only received usual care. At baseline and after 20 wk, body composition (dual-energy x-ray absorptiometry), muscle mass (computed tomography scan), muscle strength (1-repetition maximum strength tests), physical performance (Timed Up and Go Test, 30-Second Chair Stand Test, and Stair Climb Test), aerobic capacity (cardiopulmonary exercise test), and habitual dietary intake (food diary) were assessed. Data were analyzed using a two-factor repeated-measures ANOVA. RESULTS: Over time, muscle mass and strength increased in EX + PRO and EX + PLA and decreased in CON. Total fat mass and fat percentage increased in EX + PRO and CON, but not in EX + PLA. Physical performance did not significantly change over time in either group. Aerobic capacity was maintained in EX + PLA, but it decreased in EX + PRO and CON. Habitual protein intake (without supplements) averaged >1.0 g·kg body weight -1 ·d -1 , with no differences over time or between groups. CONCLUSIONS: In prostate cancer patients, resistance exercise training counteracts the adverse effects of ADT on body composition, muscle mass, muscle strength, and aerobic capacity, with no additional benefits of protein supplementation.

A Prospective Multicenter Comparison Study of Risk-adapted Ultrasound-directed and Magnetic Resonance Imaging-directed Diagnostic Pathways for Suspected Prostate Cancer in Biopsy-naïve Men.

BACKGROUND: European Association of Urology guidelines recommend a risk-adjusted biopsy strategy for early detection of prostate cancer in biopsy-naïve men. It remains unclear which strategy is most effective. Therefore, we evaluated two risk assessment pathways commonly used in clinical practice. OBJECTIVE: To compare the diagnostic performance of a risk-based ultrasound (US)-directed pathway (Rotterdam Prostate Cancer Risk Calculator [RPCRC] #3; US volume assessment) and a magnetic resonance imaging (MRI)-directed pathway. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective multicenter study (MR-PROPER) with 1:1 allocation among 21 centers (US arm in 11 centers, MRI arm in ten). Biopsy-naïve men with suspicion of prostate cancer (age ≥50 yr, prostate-specific antigen 3.0-50 ng/ml, ± abnormal digital rectal examination) were included. INTERVENTION: Biopsy-naïve men with elevated risk of prostate cancer, determined using RPCRC#3 in the US arm and Prostate Imaging Reporting and Data System scores of 3-5 in the MRI arm, underwent systematic biopsies (US arm) or targeted biopsies (MRI arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of men with grade group (GG) ≥2 cancer. Secondary outcomes were the proportions of biopsies avoided and GG 1 cancers detected. Categorical (nonparametric) data were assessed using the Mann-Whitney U test and χ2 tests. RESULTS AND LIMITATIONS: A total of 1965 men were included in the intention-to-treat population (US arm n = 950, MRI arm n = 1015). The US and MRI pathways detected GG ≥2 cancers equally well (235/950, 25% vs 239/1015, 24%; difference 1.2%, 95% confidence interval [CI] -2.6% to 5.0%; p = 0.5). The US pathway detected more GG 1 cancers than the MRI pathway (121/950, 13% vs 84/1015, 8.3%; difference 4.5%, 95% CI 1.8-7.2%; p < 0.01). The US pathway avoided fewer biopsies than the MRI pathway (403/950, 42% vs 559/1015, 55%; difference -13%, 95% CI -17% to -8.3%; p < 0.01). Among men with elevated risk, more GG ≥2 cancers were detected in the MRI group than in the US group (52% vs 43%; difference 9.2%, 95% CI 3.0-15%; p < 0.01). CONCLUSIONS: Risk-adapted US-directed and MRI-directed pathways detected GG ≥2 cancers equally well. The risk-adapted US-directed pathway performs well for prostate cancer diagnosis if prostate MRI capacity and expertise are not available. If prostate MRI availability is sufficient, risk assessment should preferably be performed using MRI, as this avoids more biopsies and detects fewer cases of GG 1 cancer. PATIENT SUMMARY: Among men with suspected prostate cancer, relevant cancers were equally well detected by risk-based pathways using either ultrasound or magnetic resonance imaging (MRI) to guide biopsy of the prostate. If prostate MRI availability is sufficient, risk assessment should be performed with MRI to reduce unnecessary biopsies and detect fewer irrelevant cancers.

Study protocol of a phase II clinical trial of oral metformin for the intravesical treatment of non-muscle invasive bladder cancer.

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) is the most common neoplasm of the urinary tract and requires life-long invasive surveillance to detect disease recurrence. Currently, there are no effective oral therapies that delay disease recurrence or progression. We recently demonstrated that in mice, metformin accumulates unchanged in the urine. Urothelial cells are exposed to metformin concentrations ~ 240-fold higher than in serum. This was effective in the treatment of mouse bladder cancer models. METHODS: We describe the protocol of a multi-centre, open-label, phase II clinical trial of metformin in up to 49 evaluable patients with intermediate-risk NMIBC with the aim to determine the overall response to administration of oral metformin for 3 months on a marker tumour deliberately left following transurethral resection of multiple, papillary NMIBC tumours. All patients will receive metformin orally at doses up to 3000 mg per day. Metformin treatment will start within 2 weeks following transurethral resection of all tumours except one marker lesion. After 3 months of metformin treatment, the effect of metformin on the marker lesion is evaluated by cystoscopy and biopsy under anaesthesia. Residual tumour, if present at this evaluation, will be resected. In case of complete disappearance of the marker lesion, the former tumour area will be biopsied. The primary outcome is the complete response rate of the marker lesion, as determined by decentralised scoring of pre- and post-treatment cystoscopy images by expert independent urologists. Secondary outcomes are the partial response rate, overall safety of metformin and the duration of the time to recurrence. DISCUSSION: Preclinical studies show the potential role of oral metformin treatment in the management of NMIBC. It could offer an alternative to current adjuvant intravesical treatment. If positive, the reported results of this study could warrant further phase III trials to compare the efficacy of metformin against current treatments of intravesical installations with chemotherapy or Bacillus Calmette-Guérin (BCG). TRIAL REGISTRATION: This trial is registered in ClinicalTrials.gov under NCT03379909.

Impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) on prostate-specific antigen (PSA) testing by Dutch general practitioners.

OBJECTIVE: To determine the impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) publication in 2009 on prostate-specific antigen (PSA) level testing by Dutch general practitioners (GPs) in men aged ≥40 years. MATERIALS AND METHODS: Retrospective study with a Dutch insurance company database (containing PSA test claims) and a large district hospital-laboratory database (containing PSA-test results). The difference in primary PSA-testing rate as well as follow-up testing before and after the ERSPC was tested using the chi-square test with statistical significance at P < 0.05. RESULTS: Decline in PSA tests 4 months after ERSPC publication, especially for men aged ≥60 years. Primary testing as well as follow-up testing decreased, both for PSA levels of <4 ng/mL as well as for PSA levels of 4-10 ng/mL. Follow-up testing after a PSA level result of >10 ng/mL moderately increased (P = 0.171). Referral to a urologist after a PSA level result of >4 ng/mL decreased slightly after the ERSPC publication (P = 0.044). CONCLUSIONS: After the ERSPC publication primary PSA testing as well as follow-up testing decreased. Follow-up testing seemed not to be adequate after an abnormal PSA result. The reasons for this remain unclear.

Prostate specific antigen testing policy worldwide varies greatly and seems not to be in accordance with guidelines: a systematic review.

BACKGROUND: Prostate specific antigen (PSA) testing is widely used, but guidelines on follow-up are unclear. METHODS: We performed a systematic review of the literature to determine follow-up policy after PSA testing by general practitioners (GPs) and non-urologic hospitalists, the use of a cut-off value for this policy, the reasons for repeating a PSA test after an initial normal result, the existence of a general cut-off value below which a PSA result is considered normal, and the time frame for repeating a test. Data sources. MEDLINE, Embase, PsychInfo and the Cochrane library from January 1950 until May 2011. Study eligibility criteria. Studies describing follow-up policy by GPs or non-urologic hospitalists after a primary PSA test, excluding urologists and patients with prostate cancer. Studies written in Dutch, English, French, German, Italian or Spanish were included. Excluded were studies describing follow-up policy by urologists and follow-up of patients with prostate cancer. The quality of each study was structurally assessed. RESULTS: Fifteen articles met the inclusion criteria. Three studies were of high quality. Follow-up differed greatly both after a normal and an abnormal PSA test result. Only one study described the reasons for not performing follow-up after an abnormal PSA result. CONCLUSIONS: Based on the available literature, we cannot adequately assess physicians' follow-up policy after a primary PSA test. Follow-up after a normal or raised PSA test by GPs and non-urologic hospitalists seems to a large extent not in accordance with the guidelines.

Bilateral macrodystrophia lipomatosa of the upper extremities with syndactyly and multiple lipomas.

Macrodystrophia lipomatosa is a rare disease that causes congenital local gigantism of part of an extremity, which is characterised by an increase in all mesenchymal elements, particularly fibroadipose tissue. This is the first report to our knowledge of a case of histologically confirmed bilateral macrodystrophia lipomatosa of the upper extremities with syndactyly and multiple lipomas.

Modified distal revascularization with interval ligation procedure for steal syndrome after arteriovenous fistula creation for hemodialysis access.

Patients diagnosed with steal syndrome after hemodialysis access surgery have a few options for symptom relief while maintaining vascular access. These include fistula lengthening, banding, distal revascularization with interval ligation (DRIL), revision using distal inflow (RUDI) or proximalization of the arterial inflow (PAI). Two cases are described in which a modified DRIL procedure without interval ligation was used to relieve steal syndrome, leaving the arterial supply of an ischemic hand not entirely dependent upon a bypass. Furthermore, a review of the literature is presented in order to elucidate this relatively new treatment option as a viable means to improve hand perfusion while maintaining a functional fistula.