Background Androgen deprivation therapy (ADT) for prostate cancer with luteinizing hormone-releasing hormone (LHRH) agonists can be improved. Objective To assess safety, the frequency and severity of hot flushes (HFs), bone health, and antitumor effects of high-dose estetrol (HDE4) when combined with ADT. Design, setting and participants A phase II, double-blind, randomized, placebo-controlled study was conducted in advanced prostate cancer patients requiring ADT (the PCombi study). Intervention Patients receiving LHRH agonist treatment were randomized 2:1 to 40 mg HDE4 ( n = 41) or placebo ( n = 21) cotreatment for 24 wk. Outcome measurements and statistical analysis Coprimary endpoints were frequency/severity of HFs and levels of total and free testosterone (T). Secondary endpoints included assessments of bone metabolism (osteocalcin and type I collagen telopeptide [CTX1]), prostate-specific antigen (PSA), and follicle-stimulating hormone (FSH). Efficacy analysis was based on the selected per-protocol (PP) population. Results and limitations Of 62 patients included in the study, 57 were suitable for a PP analysis (37 HDE4; 20 placebo). No E4-related serious cardiovascular adverse events occurred at 24 wk. Weekly HFs were reported by 13.5% of patients with HDE4 and 60.0% with placebo ( p < 0.001). Daily HFs occurred in 5.9% versus 55%. Bone turnover parameters decreased significantly with HDE4 ( p < 0.0001). Total and free T decreased earlier ( p < 0.05), and free T was suppressed further ( p < 0.05). PSA suppression was more profound and earlier ( p < 0.005). FSH levels were suppressed by 98% versus 57% ( p < 0.0001). Estrogenic side effects were nipple sensitivity (34%) and gynecomastia (17%). Conclusions HDE4 cotreatment of ADT patients with advanced prostate cancer was well tolerated, and no treatment-related cardiovascular adverse events were observed at 24 wk. HFs and bone turnover were substantially reduced. Suppression of free T, PSA, and FSH was more rapid and profound, suggesting enhanced disease control by HDE4 cotreatment. Larger and longer-lasting studies are needed to confirm the results of the study reported here. Patient summary Cotreatment of androgen deprivation therapy with high-dose estetrol in advanced prostate cancer patients results in fewer occurrences of hot flushes, bone protection, and other antitumor benefits. Nipple sensitivity and gynecomastia may occur as side effects.

OBJECTIVE To determine the long‐term efficacy of endoscopically implanting polydimethylsiloxane (PDS, Macroplastique®, Uroplasty BV, Geleen, the Netherlands) for treating vesico‐ureteric reflux (VUR) in children. PATIENTS AND METHODS We retrospectively reviewed the records of 195 children treated with PDS over the past 10 years in two European centres (Netherlands and UK) and conducted follow‐up investigations where deemed necessary. In the Dutch centre patients were treated according to a prospective approved study protocol. RESULTS Of the 195 treated children, 155 had a successful outcome; in all, 311 refluxing renal units were treated, with an overall success rate of 82.3% in a mixed group of patients with unilateral or bilateral VUR and duplex systems. CONCLUSION The long‐term data from these two independent centres confirms the viability of PDS and the technique for treating VUR in children. We conclude that the material is safe and effective and can be used in VUR grades II–V. Treating patients with grade I VUR is recommended in those cases where there is no spontaneous resolution and ‘breakthrough’ infections.

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Introduction: [ 18 F]-fluoro-methylcholine (FCH) PET/CT and MRI with diffusion-weighted MRI (DW-MRI) have insufficient performance in lymph node staging of primary prostate cancer by themselves, but the combination may perform better. We aim to prospectively determine the diagnostic performance of combined FCH PET and MRI for lymph node staging. Methods: This was a single site study of diagnostic accuracy in a well-defined group of 21 consecutive high-risk primary prostate cancer patients (>30% chance of lymph node metastases) in a large community hospital. We performed FCH PET/CT and MRI with DW-MRI prior to endoscopic extended pelvic lymph node dissection (EPLND). PET was fused and interpreted together with various MRI image sets (T1, T2, DWIBS) and was only scored positive when a lymph node seen on MRI coincided with increased focal FCH uptake on PET. Findings were compared with detailed histological evaluation, on a per-patient and per-region level. We calculated sensitivity, specificity, positive and negative predictive value of combined PET-MRI. Results: 14 out of 21 patients had metastatic lymph nodes with 37 out of 164 evaluable regions harboring metastases. On a per-patient analysis, PET-MRI had a sensitivity/specificity of 79/100% with a PPV/NPV of 100/77%. On a per-region analysis (n = 164) these figure were 65/99% and 96/91%, respectively. Conclusions: Combined DW-MRI and FCH PET/CT has a very high positive predictive value in high risk prostate cancer patients. If confirmed in larger series a positive combined scan may safely allow cancellation of surgical staging