Background:Although statins do not affect the incidence of prostate cancer (CaP), usage reduces the risk of clinical progression and mortality. Although statins are known to downregulate the mevalonate pathway, the mechanism by which statins reduce CaP progression is unknown.Methods:Bone marrow stroma (BMS) was isolated with ethical approval from consenting patients undergoing surgery for non-malignant disease. PC-3 binding, invasion and colony formation within BMS was assessed by standardised in vitro co-culture assays in the presence of different statins.Results:Statins act directly on PC-3 cells with atorvastatin, mevastatin, simvastatin (1 μℳ) and rosuvastatin (5 μℳ), but not pravastatin, significantly reducing invasion towards BMS by an average of 66.68% (range 53.93–77.04% P<0.05) and significantly reducing both number (76.2±8.29 vs 122.9±2.48; P=0.0055) and size (0.2±0.0058 mm2 vs 0.27±0.012 mm2; P=0.0019) of colonies formed within BMS. Statin-treated colonies displayed a more compact morphology containing cells of a more epithelial phenotype, indicative of a reduction in the migrational ability of PC-3 cells. Normal PC-3 phenotype and invasive ability was recovered by the addition of geranylgeranyl pyrophosphate (GGPP).Conclusion:Lipophilic statins reduce the migration and colony formation of PC-3 cells in human BMS by inhibiting GGPP production, reducing the formation and the spread of metastatic prostate colonies.

Study Type – Preference (prospective cohort)
Level of Evidence 1b What’s known on the subject? and What does the study add? In general the literature suggests that there is a need for improvement in aiding men diagnosed with early prostate cancer in their decision making about treatment options and that our understanding of this process is inadequate. There is limited data analyzing the reasons why these men decide between potentially curative or observational treatments and data evaluating patients’ views before and after definitive therapy are scarce. This study begins the process of understanding the reasons underlying a patient’s final treatment decision. Being a prospective study, it looks at the thought processes of these men before treatment during the time the decision is made. It also documents how satisfied patients are with their choice after their treatment and whether they would choose the same treatment again. OBJECTIVE • To identify the reasons for patients with localised prostate cancer choosing between treatments and the relationship of procedure type to patient satisfaction post‐treatment. PATIENTS AND METHODS • 768 men with prostate cancer (stage T1/2, Gleason ≤7, PSA <20 ug/L) chose between four treatments: radical prostatectomy, brachytherapy, conformal radiotherapy and active surveillance. • Prior to choosing, patients were counselled by a urological surgeon, clinical (radiation) oncologist and uro‐oncology specialist nurse. • Pre‐treatment reasons for choice were recorded. Post‐treatment satisfaction was examined via postal questionnaire. RESULTS • Of the 768 patients, 305 (40%) chose surgery, 237 (31%) conformal beam radiotherapy, 165 (21%) brachytherapy and 61 (8%) active surveillance. • Sixty percent of men who opted for radical prostatectomy were motivated by the need for physical removal of the cancer. • Conformal radiotherapy was mainly chosen by patients who feared other treatments (n = 63, 27%). Most men chose brachytherapy because it was more convenient for their lifestyle (n = 64, 39%). • Active surveillance was chosen by patients for more varied reasons. Post‐treatment satisfaction was assessed in a subgroup who took part in the QOL aspect of this study. • Of the respondents to the questionnaire, 212(87.6%) stated that they were satisfied/extremely satisfied with their choice and 171(92.9%) indicated they would choose the same treatment again. CONCLUSION • Men with early prostate cancer have clear reasons for making decisions about treatment. Overall, patients were satisfied with the treatment and indicated that despite different reasons for choosing treatment, they would make the same choice again.

Background The prostate cancer (PCa) diagnostic pathway is undergoing a radical change with the introduction of multiparametric magnetic resonance imaging (mpMRI), genomic testing, and different prostate biopsy techniques. It has been proposed that these tests should be used in a sequential manner to optimise risk stratification. Objective To characterise the genomic, epigenomic, and transcriptomic features of mpMRI-visible and -nonvisible PCa in clinically localised disease. Design, setting, and participants Multicore analysis of fresh prostate tissue sampled immediately after radical prostatectomy was performed for intermediate- to high-risk PCa. Intervention Low-pass whole-genome, exome, methylation, and transcriptome profiling of patient tissue cores taken from microscopically benign and cancerous areas in the same prostate. Circulating free and germline DNA was assessed from the blood of five patients. Outcome measurement and statistical analysis Correlations between preoperative mpMRI and genomic characteristics of tumour and benign prostate samples were assessed. Gene profiles for individual tumour cores were correlated with existing genomic classifiers currently used for prognostication. Results and limitations A total of 43 prostate cores (22 tumour and 21 benign) were profiled from six whole prostate glands. Of the 22 tumour cores, 16 were tumours visible and six were tumours nonvisible on mpMRI. Intratumour genomic, epigenomic, and transcriptomic heterogeneity was found within mpMRI-visible lesions. This could potentially lead to misclassification of patients using signatures based on copy number or RNA expression. Moreover, three of the six cores obtained from mpMRI-nonvisible tumours harboured one or more genetic alterations commonly observed in metastatic castration-resistant PCa. No circulating free DNA alterations were found. Limitations include the small cohort size and lack of follow-up. Conclusions Our study supports the continued use of systematic prostate sampling in addition to mpMRI, as avoidance of systematic biopsies in patients with negative mpMRI may mean that clinically significant tumours harbouring genetic alterations commonly seen in metastatic PCa are missed. Furthermore, there is inconsistency in individual genomics when genomic classifiers are applied. Patient summary Our study shows that tumour heterogeneity within prostate tumours visible on multiparametric magnetic resonance imaging (mpMRI) can lead to misclassification of patients if only one core is used for genomic analysis. In addition, some cancers that were missed by mpMRI had genomic aberrations that are commonly seen in advanced metastatic prostate cancer. Avoiding biopsies in mpMRI-negative cases may mean that such potentially lethal cancers are missed.

The nature and extent of the obstructing lesion and its potential for further treatment are the major determinants of post-nephrostomy survival. Every effort should therefore be made to identify the nature of the obstruction before deciding on PND.