Context. The optimal treatment for men with high-risk localized or locally advanced prostate cancer (PCa) remains unknown. Objective. To perform a systematic review of the existing literature on the effectiveness of the different primary treatment modalities for high-risk localized and locally advanced PCa. The primary oncological outcome is the development of distant metastases at ≥5 years of follow-up. Secondary oncological outcomes are prostate cancer specific mortality (PCSM), overall mortality (OM), biochemical recurrence and need for salvage treatment with ≥5 years of follow-up. Non-oncological outcomes are quality of life (QoL), functional outcomes and treatment-related side effects reported. Evidence acquisition. Medline, Medline In-Process, Embase, and the Cochrane Central Register of Randomized Controlled Trials were searched. All comparative (randomized and non-randomized) studies published between January 2000 and May 2019 with at least 50 participants in each arm were included. Studies reporting on high-risk localized PCa (ISUP grade 4-5 [GS 8-10] or PSA >20 ng/mL or ≥cT2c) and/or locally advanced PCa (any PSA, cT3-4 or cN+, any ISUP grade/ GS score) or where subanalyses were performed on either group were included. The following primary local treatments were mandated: radical prostatectomy (RP), external beam radiotherapy (EBRT) (≥64 Gy), brachytherapy (BT) or multimodality treatment combining any of the local treatments above (+/-any systemic treatment). Risk of Bias (RoB) and confounding factors were assessed for each study. A narrative synthesis was performed. Evidence synthesis. Overall, 90 studies met the inclusion criteria. RoB and confounding factors revealed high RoB for selection, performance and detection bias and low RoB for correction of initial PSA and biopsy GS. When comparing RP to EBRT, retrospective series suggested an advantage for RP, although with a low level of evidence. Both RT and RP should be seen as part of a multimodal treatment plan with possible addition of (post-operative) RT and/or ADT respectively. High levels of evidence exist for EBRT treatment with several RCTs showing superior outcome for adding long-term ADT or BT to EBRT. No clear cutoff can be proposed for RT dose but higher RT doses by means of dose escalation schemes result in an improved biochemical control. Twenty studies reported data on QoL, with RP resulting mainly in GU toxicity and sexual dysfunction, and EBRT in bowel problems. Conclusion. Based on the results of this systematic review, both RP as part of multimodal treatment and EBRT + long-term ADT can be recommended as primary treatment in high-risk and locally advanced PCa. For high-risk PCa, also EBRT + BT can be offered, despite more grade 3 toxicity. Interesting, for selected patients, e.g. with higher comorbidity, a shorter duration of ADT might be an option. For locally advanced PCa, EBRT + BT shows promising result but still needs further validation. In this setting, it is important that patients are aware that the offered therapy will be mos...

Introduction: Mi(cro)RNAs are small non-coding RNAs whose differential expression in tissue has been implicated in the development and progression of many malignancies, including prostate cancer. The discovery of miRNAs in the blood of patients with a variety of malignancies makes them an ideal, novel biomarker for prostate cancer diagnosis. The aim of this study was to identify a unique expression profile of circulating miRNAs in patients with prostate cancer attending a rapid access prostate assessment clinic. Methods: To conduct this study blood and tissue samples were collected from 102 patients (75 with biopsy confirmed cancer and 27 benign samples) following ethical approval and informed consent. These patients were attending a prostate assessment clinic. Samples were reverse-transcribed using stem-loop primers and expression levels of each of 12 candidate miRNAs were determined using real-time quantitative polymerase chain reaction. miRNA expression levels were then correlated with clinicopathological data and subsequently analysed using qBasePlus software and Minitab. Results: Circulating miRNAs were detected and quantified in all subjects. The analysis of miRNA mean expression levels revealed that four miRNAs were significantly dysregulated, including let-7a (p = 0.005) which has known tumour suppressor characteristics, along with miR-141 (p = 0.01) which has oncogenic characteristics. In 20 patients undergoing a radical retropubic-prostatectomy, the expression levels of miR-141 returned to normal at day 10 post-operatively. A panel of four miRNAs could be used in combination to detect prostate cancer with an area under the curve (AUC) of 0.783 and a PPV of 80%. Conclusion: These findings identify a unique expression profile of miRNA detectable in the blood of prostate cancer patients. This confirms their use as a novel, diagnostic biomarker for prostate cancer.

Fear of predators can behaviorally mediate prey population dynamics, particularly when predation risk influences reproductive investment. However, the costs of reproductive investment may mitigate predation risk aversion relative to periods when the link between reproductive output and prey behavior is weaker. We posit that intensity of reproductive investment in ungulates may predict their response to predation risk such that the sexes increase risk exposure during biological seasons that are pivotal to reproductive success, such as the fawn‐rearing and breeding seasons for females and males, respectively. We examined the activity patterns of sympatric white‐tailed deer (Odocoileus virginianus), a sexually segregated polygynous ungulate, and Florida panthers (Puma concolor coryi) in the context of the “risky times – risky places hypothesis” and the reproductive strategy hypothesis. We compared detection rates and diel activity overlap of both species using motion‐triggered camera traps positioned on (n = 120) and off (n = 60) anthropogenic trails across five reproductive seasons. Florida panthers were nocturnal and primarily observed on‐trail providing an experimental framework with risky times and risky places. Contrary to studies in other taxa inversely correlating prey reproductive investment to predation risk, the sexes of deer were more risk prone during sex‐specific seasons associated with intense reproductive investment. Our results suggest spatiotemporally variable predation risk influences sex‐specific behavioral decision‐making in deer such that reproductive success is maximized.

BackgroundThe acquisition of procedural skills is an essential component of learning for medical trainees. The objective of this study was to assess which teaching method of performing urinary catheterisation is associated with most efficient procedural skill acquisition and retention. We evaluated factors affecting acquisition and retention of skills when using simulators as adjuncts to medical training.MethodsForty-two second year medical students were taught urinary catheter insertion using different teaching methods. The interactive group (n = 19) were taught using a lecture format presentation and a high fidelity human urinary catheter simulator. They were provided with the use of simulators prior to examination. The observer group (n = 12) were taught using the same method but without with simulator use prior to examination. The didactic group (n = 11) were taught using the presentation alone. Student characteristics such as hand dexterity and IQ were measured to assess for intrinsic differences. All students were examined at four weeks to measure skill retention.ResultsCatheter scores were significantly higher in the interactive group (p < 0.005). Confidence scores with catheter insertion were similar at index exam however were significantly lower in the didactic group at the retention testing (p < 0.05). Retention scores were higher in the interactive group (p < 0.001). A significant positive correlation was observed between laparoscopy scores and time to completion with overall catheter score (p < 0.05). Teaching method, spatial awareness and time to completion of laparoscopy were significantly associated with higher catheter scores at index exam (p = 0.001). Retention scores at 4 weeks were significantly associated with teaching method and original catheter score (p = 0.001).ConclusionThe importance of simulators in teaching a complex procedural skill has been highlighted. Didactic teaching method was associated with a significantly higher rate of learning decay at retention testing.Electronic supplementary materialThe online version of this article (doi:10.1186/s12909-014-0264-3) contains supplementary material, which is available to authorized users.