Are all gonadotrophin-releasing hormone agonists equivalent for the treatment of prostate cancer? A systematic review.

To review direct comparative studies of the gonadotrophin-releasing hormone (GnRH) agonists goserelin, triptorelin, and leuprorelin for the treatment of prostate cancer, and identify whether there are meaningful clinical differences between these agents. In June 2017, the following searches were performed independently by two reviewers in PubMed: (i) 'prostate cancer' and 'triptorelin' and 'leuprorelin', (ii) 'prostate cancer' and 'triptorelin' and 'goserelin', and (iii) 'prostate cancer' and 'goserelin' and 'leuprorelin', without time restriction. Duplicates were deleted. Relevant conference abstracts were also screened. A total of 16 direct comparative trials were identified: 12 reported on efficacy outcomes, four on safety/tolerability, and five on the convenience of administration/user perceptions. These studies are restricted in terms of patient numbers, formulations assessed, and endpoints measured; none were adequately powered for survival outcome measures. Studies reporting on efficacy endpoints did not show major differences in the ability of these GnRH agonists to reduce levels of testosterone or prostate-specific antigen. Some studies suggest differences in short- or long-term testosterone control, the rate of injection site adverse events, and patient/healthcare professional perceptions, but definitive conclusions cannot be drawn from the existing evidence. Few direct comparative trials of GnRH agonists have been conducted. Whilst GnRH agonists provide a similar castration effect, there is not enough evidence to show that GnRH agonists are equivalent.

The transobturator suburethral sling: a safe and effective option for all degrees of post prostatectomy urinary incontinence.

INTRODUCTION: Male stress urinary incontinence (SUI) after radical prostatectomy (RP) is common. The surgical standard of care traditionally has been placement of an artificial urinary sphincter (AUS) but since its introduction the transobturator male sling has been shown to have particular unique advantages. Our aim was to assess outcomes of a consecutive series of suburethral sling insertions in men presenting with all degrees of post RP SUI. MATERIALS AND METHODS: A consecutive cohort of men undergoing AdVance sling insertion following RP were studied. Parameters assessed included pre and postoperative urinary function, 24 hour pad use, quality of life (QoL) outcomes, complications and further treatments. Degree of incontinence was categorized as mild (1-2), moderate (3-5) or severe (≥ 6) depending on daily pad use. Patients were reviewed at 1, 4 and 6 months. The International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) was used to assess symptom severity and QoL outcomes. RESULTS: Seventy-seven patients were included, mean age 68 and mean time to sling post RP 34 (8-113) months. Preoperative degree of incontinence: mild 22%, moderate 58%, severe 20%. Fourteen percent had undergone post RP radiation therapy (RT). In total 73% experienced complete resolution of symptoms post sling, 12% significant improvement, 15% no reduction in pad use. Sixty percent with severe incontinence were classified as cured (no pad or 1 dry pad for security reasons). When patients with preoperative RT were excluded, cure rate rose to 82%. On follow up survey at 30 months (mean), the ICIQ-SF score decreased from baseline 17.7 (9-21.0) to 8.0 (0-20) (p < 0.0001), CI 95% (8-12). CONCLUSIONS: Suburethral slings are effective and safe for all degrees of post RP incontinence, are associated with improved QoL parameters and with appropriate selection and counseling are a viable option for more severe degrees of post RP SUI.

Noncoding RNAs in prostate cancer: the long and the short of it.

As the leading culprit in cancer incidence for American men, prostate cancer continues to pose significant diagnostic, prognostic, and therapeutic tribulations for clinicians. The vast spectrum of disease behavior warrants better molecular classification to facilitate the development of more robust biomarkers that can identify the more aggressive and clinically significant tumor subtypes that require treatment. The untranslated portion of the human transcriptome, namely noncoding RNAs (ncRNA), is emerging as a key player in cancer initiation and progression and boasts many attractive features for both biomarker and therapeutic research. Genetic linkage studies show that many ncRNAs are located in cancer-associated genomic regions that are frequently deleted or amplified in prostate cancer, whereas aberrant ncRNA expression patterns have well-established links with prostate tumor cell proliferation and survival. The dysregulation of pathways controlled by ncRNAs results in a cascade of multicellular events leading to carcinogenesis and tumor progression. The characterization of RNA species, their functions, and their clinical applicability is a major area of biologic and clinical importance. This review summarizes the growing body of evidence, supporting a pivotal role for ncRNAs in the pathogenesis of prostate cancer. We highlight the most promising ncRNA biomarkers for detection and risk stratification and present the state-of-play for RNA-based personalized medicine in treating the "untreatable" prostate tumors.

Long noncoding RNAs and prostate carcinogenesis: the missing 'linc'?

Long noncoding RNAs (lncRNAs) are rapidly becoming essential pieces in the cancer puzzle. Our understanding of their functional capabilities is in its infancy. One certain fact, however, is that their molecular interactions extend beyond chromatin complexes into diverse biological processes. In prostate cancer, aberrant expression of lncRNAs is associated with disease progression. Overexpression of oncogenic lncRNAs promotes tumor-cell proliferation and metastasis through chromatin looping and distal engagement with the androgen receptor, antisense gene regulation, alternative splicing, and impeding DNA repair. Several lncRNAs, such as prostate cancer antigen 3 (PCA3), prostate cancer gene expression marker 1 (PCGEM1), and prostate cancer associated ncRNA transcript 1 (PCAT1), are highly prostate-specific, posing as attractive biomarkers. Herein we review the mechanisms of action of lncRNAs in prostate carcinogenesis and their potential clinical utility for disease.