Zhuang Tang

LDL-lowering therapy and the risk of prostate cancer: a meta-analysis of 6 randomized controlled trials and 36 observational studies

The role of statins in preventing prostate cancer is currently a controversial issue. The aim of this review is to investigate the effects of statins use on prostate cancer risk. Electronic databases (the Cochrane Library, PubMed, Medline, Embase, Web of Science, and ClinicalTrials.gov) were searched systematically up to April, 2015. Weighted averages were reported as relative risk (RR) with 95% confidence intervals (CIs). Statistic heterogeneity scores were assessed with the standard Cochran’s Q test and I2 statistic. The pooled estimates of randomized controlled trials (RCTs) and retrospective studies suggest that statins have a neutral effect on total prostate cancer (RR = 1·02, 95% CI: 0·90–1·14; and RR = 0·91, 95% CI: 0·79–1·02, respectively). This research provides no evidence to suggest that the use of statins for cholesterol lowering is beneficial for the prevention of low-grade or localized prostate cancer, although a plausible association between statins use and the reduction risk of advanced (RR = 0·87, 95% CI: 0·82–0·91) or high-grade prostate cancer (RR = 0·83, 95% CI: 0·66–0·99) is observed. Furthermore, it shows that prostate cancer risk does not statistically significant benefit from long-term statins use.

Cryosurgery would be An Effective Option for Clinically Localized Prostate Cancer: A Meta-analysis and Systematic Review

Cryosurgery (CS) has been used on patients with clinically localized PCa for more than 10 years. However, clinical studies evaluating its effectiveness and safety have reported conflicting results. This systematic assessment was performed to obtain comprehensive evidence regarding the potential benefits and safety of CS compared with those of radiotherapy (RT) and radical prostatectomy (RP), respectively. All controlled trials comparing CS with RT or RP and single-arm studies reporting results of CS therapy were identified through comprehensive searches of PubMed, the Cochrane Library and Embase. Ten publications from seven trials, with totally 1252 patients, were included in the meta-analysis, which revealed no significant differences in comparisons of CS vs RT and CS vs RP for overall survival and disease specific survival. However, a significantly lower disease-free survival could be observed for CS than RP. Moreover, a systematic review of literature focusing on comparative data of databases and materials of single-arm trials revealed satisfactory survival results in both primary and salvage CS. Our results showed that cryosurgery would be a relatively effective method for clinically localized prostate cancer with survival results comparable to radiotherapy and radical prostatectomy. However, the large percentage of complications caused by cryosurgery should be carefully monitored.

Antibiotics may not decrease prostate-specific antigen levels or prevent unnecessary prostate biopsy in patients with moderately increased prostate-specific antigen levels: A meta-analysis

OBJECTIVES To evaluate the effect of empiric antibiotics on decreasing prostate-specific antigen (PSA) levels and the possibility of avoiding unnecessary prostate biopsies (PBs). MATERIALS AND METHODS A systematic search of PubMed, Embase, and the Cochrane Library was performed to identify all randomized controlled trials (RCTs) that compared effects of empiric antibiotics with no treatment or placebo on lowering PSA levels and minimizing unnecessary PBs in patients with moderately increased PSA levels. The Cochrane Collaboration Review Manager software (RevMan 5.1.4) was used for statistical analysis. RESULTS The inclusion criteria for the study were met by 6 RCTs (1 placebo controlled and 5 no treatment controlled) involving 656 patients. The synthesized data from these RCTs indicated that there were no significant differences between the antibiotic and control groups in the PSA levels after treatment (mean difference [MD] = 0.15, 95% CI:-0.50 to 0.81, P = 0.65], number of patients with decreased PSA levels after treatment (relative risk [RR] = 1.22, 95% CI: 0.90-1.65, P = 0.20], prostate-specific antigen density levels after treatment (MD =-0.04, 95% CI:-0.15 to 0.07, P = 0.47), f/t% PSA after treatment (MD =-1.47, 95% CI:-4.65 to 1.71, P = 0.37), number of patients with responsive PSA (RR = 1.02, 95% CI: 0.58-1.81, P = 0.94), and individual Pca-positiverate in these patients (RR = 1.07, 95% CI: 0.53-2.16, P = 0.86), and Pca-positiverates (RR = 0.85, 95% CI: 0.48-1.50, P = 0.57). However, the antibiotic group had a significant change in the net PSA decrease after treatment compared with the control group (MD = 1.44, 95% CI: 0.70-2.17, P = 0.0001). CONCLUSION The use of empiric antibiotics may not significantly decrease PSA levels or avoid unnecessary PBs.

Prophylactic Antibiotics in Prostate Biopsy: A Meta-Analysis Based on Randomized Controlled Trials

BACKGROUND Despite frequent use of prophylactic antibiotics for patients undergoing transrectal prostate biopsy (TRPB), the incidences of urinary tract infection (UTI) and bacteria resistance are increasing. The aim of this study is to evaluate the current regimen of antimicrobial prophylaxis in TRPB. METHODS A systematic search of PubMed(®), Embase(®), and the Cochrane Library was performed to identify all randomized controlled trials (RCT) related to the effects of antibiotic prophylaxis for TRPB. The outcomes included bacteriuria, bacteremia, drug-resistant bacteria on urine/blood culture, fever, UTI, sepsis, and hospitalization. RESULTS A total of 22 RCTs with 3846 patients were identified and included. Nine trials analyzed antibiotics versus placebo/no treatment, with all outcomes substantially favoring antibiotic use (p<0.05), including bacteriuria (risk ratio [RR] 0.25, 95% confidence interval [CI] 0.15-0.42), bacteremia (RR 0.67, 95% CI 0.49-0.92), fever (RR 0.39, 95% CI 0.23-0.64), UTI (RR 0.37, 95% CI 0.22-0.62), and hospitalization (RR 0.13, 95% CI 0.03-0.55). There were no substantial differences between long-course versus short-course treatment and single versus multiple dose respectively, except for a greater risk of bacteriuria for short-course treatment (RR 2.09, 95% CI 1.17-3.73, p=0.01) and single-dose treatment (RR 1.98, 95% CI 1.18-3.33, p=0.01). There were no substantial differences among the groups for bacteriuria, fever, UTI, and hospitalization, when comparing oral versus systemic administration of antibiotics. The efficacy of several classes of antibiotics was compared without any difference among them. Despite the lack of significance, the synthesized data of three RCTs indicated a trend towards the use of combined antibiotics. CONCLUSIONS Prophylactic antibiotics could be beneficial for the reduction of infective complications after TRPB. Single-dose or short-course oral administration with any type of antibiotic appears to be optimal. One additional type of antibiotic added to the basic antibiotic agent may contribute to the minimization of severe infection and drug resistance.

The effect of statins on prostate cancer recurrence and mortality after definitive therapy: a systematic review and meta-analysis

In this work, we aim to further analyze the association of statins use with biochemical recurrence (BCR) of prostate cancer (PCa) and PCa-specific mortality after definitive therapy. A systematic literature search of PubMed, MEDLINE, and EMBASE through Jul 2015 was conducted. Pooled Hazard ratio (HR) estimates with corresponding 95% confidence intervals (CIs) were calculated using random-effects model. STATA version 10 (Stata corporation, college station, TX) was employed to conduct all statistical analyses. A total of 22 and 8 studies contributed to the biochemical recurrence analysis and PCa-specific mortality, respectively. 13 trials were included for BCR-free survival analysis. The combined result showed statins users had lowered 12% BCR risk of PCa compared with non-users (HR = 0.88, 95%CI: 0.765–0.998) (p < 0.05). The association was null among the men who underwent radical prostatectomy as primary therapy (HR = 0.96, 95%CI: 0.83–1.09), while the improved outcomes had be seen among patients who received radiation therapy (HR = 0.67, 95%CI: 0.48–0.86). After excluding the patients undergoing ADT, participants did not benefit from statins use (HR = 0.94, 95%CI: 0.77–1.11). Meanwhile, long-term statins using did not alter recurrence risk. A lower risk of prostate cancer-specific mortality was observed among statins users (HR = 0.68, 95%CI: 0.56–0.80). There was a plausible trend towards increasing the BCR-free survival rate among statins users.

Comparison between thulium laser resection of prostate and transurethral plasmakinetic resection of prostate or transurethral resection of prostate.

Benign prostatic hyperplasia (BPH) is one of the most common diseases in middle-aged and elderly men. In the present study, we aimed to compare the efficacy and safety of thulium laser resection of the prostate (TMLRP) with either transurethral plasmakinetic resection of the prostate (TUPKP) or transurethral resection of the prostate (TURP). A literature search was performed, eventually, 14 studies involving 1587 patients were included. Forest plots were produced by using Revman 5.2.0 software. Our meta-analysis showed that operation time, decrease in hemoglobin level, length of hospital stay, catheterization time, and development of urethral stricture significantly differed, whereas the transitory urge incontinence rate, urinary tract infection rate, and recatheterization rate did not significantly differ between TMLRP and either TURP or TUPKP. The blood transfusion rate was significantly different between TMLRP and TURP, but not between TMLRP and TUPKP. In addition, the retrograde ejaculation rate between TMLRP and TURP did not significantly differ. At 1, 3, 6, and 12 months of postoperative follow-up, the maximum flow rate, post-void residual, quality of life, and International Prostate Symptom Score did not significantly differ among the procedures. Thus, the findings of this study indicate that TMLRP may be a safe and feasible alternative.

Effect of statins type on incident prostate cancer risk： a meta-analysis and systematic review

The aim of this study is to investigate the effect of statins type or even when grouping statins by hydrophilic or hydrophobic nature on prostate cancer risk. A literature search was performed without language restrictions using the databases of PubMed (1984.1-2015.3), MEDLINE (1984.1-2015.3), and EMBASE (1990.1-2015.3). Two independent reviewers appraised eligible studies and extracted data. Weighted averages were reported as relative risk (RR) with 95% confidence intervals (CI). Statistic heterogeneity scores were assessed with the standard Cochran′s Q-test and I2 statistic. Publication bias was detected using the Begg′s and Egger′s tests. All statistical analyses were conducted by STATA version 10. Finally, fourteen studies were included in the meta-analysis. Both hydrophilic and hydrophobic statins showed no association with incidence of prostate cancer (RR = 1.00, 95% CI: 0.82-1.17; RR = 0.90, 95% CI: 0.73-1.08, respectively). Meanwhile, the risk of prostate cancer was not reduced in simvastatin (RR = 0.89, 95% CI: 0.72-1.05), pravastatin (RR = 1.02, 95% CI: 0.94-1.11), atorvastatin (RR = 0.89, 95% CI: 0.76-1.02), fluvastatin (RR = 0.99, 95% CI: 0.97-1.01), or lovastatin users (RR = 0.94, 95% CI: 0.79-1.08). The funnel plot showed that there was no publication bias. The results showed that statins had a neutral effect on prostate cancer risk; hydrophilic and hydrophobic statins as well as any subtype of statins did not affect the risk of prostate cancer.

Comparisons of regular and on-demand regimen of PED5-Is in the treatment of ED after nerve-sparing radical prostatectomy for Prostate Cancer

Phosphodiesterase type-5 inhibitors (PDE5-Is) have been recommended as first line therapy for erectile dysfunction for patients received nerve-sparing radical prostatectomy for prostate cancer. We examed the efficiency of PDE5-Is and considered the optimal application. Systematic search of PubMed, Embase and the Cochrane Library was performed to identify all the studies. We identified 103 studies including 3175 patients, of which 14 were recruited for systematic review. Compared with placebo, PDE5-Is significantly ameliorated the International Index of Erectile Function-Erectile Function domain score (IIEF) scores (MD 4.89, 95% CI 4.25–5.53, p < 0.001). By network meta-analysis, sildenafil seems to be the most efficiency with a slightly higher rate of treatment-emergent adverse events (TEATs), whereas tadalafil had the lowest TEATs. In terms of IIEF scores, regular regimen was remarkably better than on-demand (MD 3.28, 95% CI 1.67–4.89, p < 0.001). Regular use was not associated with higher proportion of patients suffering TEATs compared with on-demand (RR 1.02, 95% CI 0.90–1.16, p = 0.72). Compared with placebo, PDE5-Is manifested significantly improved treatment outcomes. Overall, regular regimen demonstrated statistically pronounced better potency than on-demand. Coupled with the comparable rate of side effects, these findings support the regular delivery procedure to be a cost-effective option for patients.

The characteristics of circular disposable devices and in situ devices for optimizing male circumcision: a network meta-analysis

In situ device (ISD) and circular disposable device (CDD) are used for optimizing male circumcision (MC), but evidence to explore the characteristics of these two devices is insufficient. In order to explore this issue systematically and provide reliable evidence, ten published randomized controlled trials (RCTs) exploring the safety and efficacy of ISDs and CDDs were included (involving 4649 men). Moderate quality of the RCTs included was found after assessment. Pairwise meta-analyses and network meta-analyses were processed in stata 13.0 and AIDDS v1.16.6 respectively. According to the outcomes that were statistically significant in both pairwise and network meta-analyses, ISD was found to have less intraoperative blood loss (IB), less operative time (OT) and less incidence of wound bleeding (WB) than conventional circumcision (CC); ISD was found to have less WB but more wound healing time (WHT) than CDD; CDD was found to have less IB and less OT than CC. CDD tended to have the best wound healing condition and least pain experience; ISD tended to have the least IB, least OT, least WB, and highest satisfaction rate. With their own superiorities in many aspects, CDD and ISD are both safe and effective devices for optimizing MC.

Aspirin and levofloxacin for the prevention of the occurrence of prostate cancer or transformation to castration-resistant prostate cancer: a two-part, open-label, randomised, controlled study

BACKGROUND The role that inflammation plays in the development of prostate cancer is unknown. We aimed to assess whether an anti-inflammatory drug or antibiotic, or both, could prevent prostate cancer occurrence and delay transformation to castration-resistant prostate cancer. METHODS This open-label, randomised, controlled trial recruited participants who had undergone a prostate biopsy in West China Hospital of Sichuan University. Participants older than 40 years pathologically confirmed not to have prostate cancer but who had a prostate with inflammatory cell infiltration were assigned to the prostate cancer prevention (PCP) trial, and those older than 50 years who had pathological results of prostate cancer and were suitable for only androgen-deprivation therapy were assigned to the castration-resistant prostate cancer prevention (C-RPCP) trial. We excluded patients with haematological disease, gastrointestinal disease, and mental illness. Participants in both phases were randomly assigned (1:1:1:1) to a blank control group (no intervention), aspirin (100 mg/day until diagnosis or progression), levofloxacin (500 mg/day for 4 weeks), or aspirin plus levofloxacin. The coprimary outcomes were the number of newly diagnosed patients with prostate cancer and castration-resistant prostate cancer, and the durations from benign disease to malignancy and from androgen-dependent prostate cancer to castration-resistant prostate cancer, analysed by intention to treat. Patients were followed up for 2 years or until prostate cancer diagnosis or castration-resistant prostate cancer diagnosis. All participants provided written informed consent. The trial was approved by the hospitals clinical trials and biomedical ethics committee. This trial is registered with ClinicalTrials.gov, number NCT02757365. FINDINGS Between May 1, 2014, and April 30, 2016, we recruited 53 patients for the PCP trial (24 assigned to control, ten to aspirin, 12 to levofloxacin, and seven to aspirin plus levofloxacin) and 80 patients for the C-RPCP trial (17 assigned to control, 22 to aspirin, 23 to levofloxacin, and 18 to aspirin plus levofloxacin). Median follow-up time was 13·03 months (IQR 7·07-19·47) for patients in the PCP trial and 18·17 months (11·40-22·34) for patients in the C-RPCP trial. In the PCP phase, none of the participants were pathologically proven to have prostate cancer at study end; therefore, the period from benign prostatic hyperplasia to prostate cancer did not differ between treatment groups (p=0·378). In the C-RPCP phase, the proportion of patients who developed castration-resistant prostate cancer did not significantly differ between groups (five [29%] with control, three [14%] with aspirin, three [13%] with levofloxacin, and three [17%] with aspirin plus levofloxacin; p=0·527). The median time from androgen-dependent prostate cancer to castration-resistant prostate cancer was 21·53 months (IQR 12·83-21·80) in the control group, 21·00 months (20·50-21·99) in the aspirin group, 16·53 months (14·68-17·00) in the levofloxacin group, and 25·00 months (21·02-25·00) in the aspirin plus levofloxacin group (p=0·222). In the C-RPCP phase, seven (41%) patients reported tumour-associated adverse events in the control group, compared with six (27%) with aspirin, five (22%) with levofloxacin, and eight (44%) with aspirin plus levofloxacin. Two (9%) patients on aspirin had drug-associated adverse effects compared with none in any of the other groups. No patients had serious complications and withdrew from the study because of adverse effects. INTERPRETATION Our data do not show that aspirin or levofloxacin help to decrease the incidence of prostate cancer occurrence, delay castration-resistant prostate cancer transformation, or reduce tumour-associated death. A longer period of follow-up and a larger number of patients are needed to draw final conclusions. FUNDING The Prostate Cancer Foundation Young Investigator Award 2013, the National Natural Science Foundation of China (81300627 and 81370855) and Programs from Science and Technology Department of Sichuan Province (2013SZ0006 and 2014JY0219).