The association of new-onset diabetes mellitus and medical therapy for benign prostatic hyperplasia: A population-based study

IntroductionBenign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms are highly prevalent in the aging male. Similarly, the prevalence of metabolic syndrome is increasing worldwide, with mounting evidence that these two common conditions share more than age as a predisposing factor. The objective of this study was to determine if medical management of BPH is associated with an increased risk of new-onset diabetes mellitus (DM) in routine care.MethodsThis population-based, retrospective cohort study expands on a parent study of linked administrative databases identifying patients diagnosed and treated for BPH between 2005 and 2015. The primary outcome of this secondary analysis was a new diagnosis of DM after the index date of BPH diagnosis. Covariates included age, dyslipidemia, hypertension, and vascular diseases. A Cox proportional hazards regression model was used for inferential statistical analysis.ResultsA total 129 223 men were identified with a BPH diagnosis and no prior history of DM. Of those men, 6390 (5%) were exposed to 5-alpha-reductase inhibitor (5-ARI), 39 592 (31%) exposed to alpha-blocker (AB), and 30 545 (24%) exposed to combination therapy. Compared to those men with no BPH medication use, those exposed to drugs had an increased risk of new DM. Men treated with combination therapy of 5-ARI and AB (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.25–1.35), 5-ARI monotherapy (HR 1.25, 95% CI 1.17–1.34), or AB monotherapy (HR 1.17, 95% CI 1.13–1.22) all were at higher risk of new DM diagnosis after adjusting for important covariates. When calculating the risk of a new diabetes diagnosis measured from the start of drug exposure, men treated with 5-ARIs had an increased risk of DM compared to AB monotherapy as the reference, with HR 1.12 (95% CI 1.03–1.21) for 5-ARI monotherapy and HR 1.20 (95% CI 1.14–1.25) for combination therapy.ConclusionsIn this large, long-term, retrospective study of men with a BPH diagnosis in routine practice, the risk of a new diagnosis of DM was greater in patients receiving medical management compared to controls. This modest but significant increased risk was highest in men treated with any 5-ARIs, in combination as well as monotherapy, compared to the ABs.     

Alcohol Intake Increases High-grade Prostate Cancer Risk Among Men Taking Dutasteride in the REDUCE Trial

Background

Although most studies found no association between alcohol intake and prostate cancer (PCa) risk, an analysis of the Prostate Cancer Prevention Trial found that high alcohol intake significantly increased PCa risk among men randomized to the 5α-reductase inhibitor (5-ARI) finasteride.

Objective

Determine whether alcohol affects PCa risk among men taking the 5-ARI dutasteride.

Design, settings, and participants

Reduction by Dutasteride of Prostate Cancer Events was a 4-yr, multicenter, randomized, double-blind, placebo-controlled trial to compare PCa after dutasteride administration (0.5 mg/d) with placebo. Participants had a baseline prostate-specific antigen between 2.5 and 10.0 ng/ml and a recent negative prostate biopsy. Alcohol intake was determined by baseline questionnaire, and participants underwent a prostate biopsy to determine PCa status at 2 yr and 4 yr of follow-up.

Outcome measurements and statistical analysis

Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between alcohol intake and low-grade (Gleason <7) and high-grade (Gleason >7) PCa.

Results and limitations

Of 6374 participants in our analysis, approximately 25% reported no alcohol consumption, 49% were moderate drinkers (one to seven drinks per week), and 26% were heavy drinkers (more than seven drinks per week). Alcohol intake was not associated with low- or high-grade PCa in the placebo arm and was not associated with low-grade PCa among men taking dutasteride. In contrast, men randomized to dutasteride and reporting more than seven drinks per week were 86% more likely to be diagnosed with high-grade PCa (p = 0.01). Among alcohol abstainers, dutasteride was associated with significantly reduced risk of high-grade PCa (OR: 0.59; 95% CI, 0.38–0.90), but dutasteride was no longer associated with reduced high-grade PCa among men reporting high alcohol intake (OR: 0.99; 95% CI, 0.67–1.45).

Conclusions

Alcohol consumption negated a protective association between dutasteride and high-grade PCa.

Patient summary

We confirmed a prior study that alcohol affects PCa prevention in patients taking 5-ARIs. Patients taking 5-ARIs may wish to eliminate alcohol intake if they are concerned about PCa.     

Localized prostate cancer: An analysis of the Centers for Disease Control and Prevention Breast and Prostate Cancer Data Quality and Patterns of Care study (CDC PoC-BP)

IntroductionLimited evidence exists on the comparative effectiveness of local treatments for prostate cancer (PCa) due to the lack of generalizability. Using granular national data, we sought to examine the association between radical prostatectomy (RP) and intensity-modulated radiation therapy (IMRT) treatment and survival.MethodsRecords were abstracted for localized PCa cases diagnosed in 2004 across seven state registries to identify patients undergoing RP (n=3019) or IMRT (n=667). Comorbidity was assessed by the Adult Comorbidity Evaluation-27 (ACE-27). Propensity score matching (PSM) was used to balance covariates between treatment groups. All-cause and PCa-specific mortality were primary endpoints. A subgroup analysis of patients with high-risk PCa (RP, n=89; IMRT, n=95) was conducted.ResultsFollowing PSM, matched patients (n=502 pairs) treated with either RP or IMRT were well-balanced with respect to covariates. With a median followup of 10.5 years (interquartile range [IQR] 9.9–11.0), the 11-year overall survival (OS) was 71.2% (95% confidence interval [CI] 66.9–75.8) for RP and 62.3% (95% CI 57.4–67.6) for IMRT. IMRT was associated with a 41% increased risk of all-cause mortality (hazard ratio [HR] 1.41, 95% CI 1.13–1.76) but not PCa-specific mortality (HR 1.75, 95% CI 0.84–3.64), as compared to RP. In patients with high-risk PCa, IMRT, as compared to RP, was not associated with a statistically significant difference in all-cause (HR 1.53, 95% CI 0.97–2.42) or PCa-specific mortality (HR 1.92, 95% CI 0.69–5.36).ConclusionsDespite a low mortality rate at 10 years and possible residual confounding, we found a significantly increased risk of all-cause mortality but no PCa-specific mortality associated with IMRT as compared to RP in this population-based study.     

The association between metabolic syndrome and advanced prostate cancer in Chinese patients receiving radical prostatectomy

The global incidence of metabolic syndrome (MetS) is dramatically increasing. Considerable interest has been devoted to the relationship between MetS and prostate cancer (PCa) risk. However, few studies have examined the association between MetS and PCa progression. This retrospective study consisted of 1016 patients with PCa who received radical prostatectomy. The association between MetS and pathological features was evaluated using logistic regression analysis. Compared with patients without MetS, those with MetS indicated an increased risk of prostatectomy Gleason score (GS) ≥8 (odds ratio [OR] =1.670, 95% confidence interval (CI) 1.096–2.545, P= 0.017), and a 1.5-fold increased risk of pT3–4 disease (OR = 1.583, 95% CI 1.106–2.266, P= 0.012). The presence of MetS was an independent predictor of lymph node involvement (OR = 1.751, 95% CI 1.038–2.955, P= 0.036). Furthermore, as the number of MetS components accumulated, the risk of a GS ≥ 8 increased. The present study indicates a significant association between MetS and advanced PCa. The results need to be evaluated in large-scale prospective cohorts.     

Prostate cancer risk and aggressiveness associated with the CYP1B1 4326C/G (Leu432Val) polymorphism: a meta-analysis of 2788 cases and 2968 controls

To derive a precise estimation of the associations between the cytochrome P450 1B1 (CYP1B1) 4326C/G variants and prostate cancer (PCa) risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYP1B1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians (OR=1.52, 95% CI: 1.20–1.92), and significant associations were also observed in a heterozygote comparison (OR=1.40, 95% CI: 1.03–1.89), a homozygote comparison (OR=2.38, 95% CI: 1.31–4.33) and in a dominant genetic model (OR=1.52, 95% CI: 1.14–2.01). Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa (OR=1.13, 95% CI: 1.04–1.24), and significant associations were observed in a heterozygote comparison (OR=1.16, 95% CI: 1.02–1.33), a homozygote comparison (OR=1.24, 95% CI: 1.03–1.49) and a dominant genetic model (OR=1.19, 95% CI: 1.05–1.34). The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYP1B1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases.     

Genetic polymorphisms in HIF1A are associated with prostate cancer risk in a Chinese population

The hypoxia-inducible factor-1α (HIF-1α) plays an important role in regulating angiogenesis, which is essential for tumor growth and metastasis. Genetic variations of HIF1A (coding HIF-1α) have been shown to influence an individual''s susceptibility to many human tumors; however, evidence on associations between HIF1A single-nucleotide polymorphisms (SNPs) and prostate cancer (PCa) risk is conflicting. We genotyped three potentially functional polymorphisms in HIF1A (rs11549465, rs11549467 and rs2057482) using the TaqMan method and assessed their associations with PCa risk in a case–control study of 662 PCa patients and 716 controls in a Chinese Han population. Compared with rs11549467 GG genotype, the variant genotypes GA+AA had a significantly increased PCa risk (adjusted odds ratio (OR)=1.70; 95% confidence interval (CI)=1.06–2.72), particularly among older patients (OR=2.01; 95%CI=1.05–3.86), smokers (OR=2.06; 95%CI=1.07–3.99), never drinkers (OR=2.16; 95%CI=1.20–3.86) and patients without a family history of cancer (OR=1.71; 95%CI=1.02–2.89). Furthermore, patients with rs11549467 variant genotypes were associated with a higher Gleason score (OR=2.14; 95%CI=1.22–3.75). No altered PCa risk was associated with the rs11549465 and rs2057482 polymorphism. However, the combined variant genotypes of rs2057482 and rs11549467 were associated with increased PCa risk (OR=2.10; 95%CI=1.23–3.57 among subjects carrying three or more risk alleles). These results suggest that HIF1A polymorphisms may impact PCa susceptibility and progression in the Chinese Han population.     

Positive association between preoperative lymphocyte-to-monocyte ratio and risk of the status of positive surgical margins by prostate cancer: results in 497 consecutive patients treated only by radical prostatectomy

BackgroundPositive surgical margins (PSM) is one of the most important factors affecting the prognosis of prostate cancer (PCa) patients after radical prostatectomy (RP). Although some studies have found the preoperative systematic inflammation-based scores the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) can predict the incidence and prognosis of PCa, few studies have explored the predictive value of preoperative systematic inflammation-based scores on the PSMs for PCa patients after RP.MethodsFrom June 2014 to September 2020 a total of 497 patients underwent RP at our institution. Blood samples from all patients were collected within one week before surgery. Preoperative clinical characteristics including age, body mass index (BMI), prostate-specific antigen (PSA), and biopsy Gleason sum (BGS) were assessed. Postoperatively pathological specimens were assessed for pathological Gleason sum (PGS), pathological stage, and margin status.ResultsIn the multivariable analysis including preoperative variables, PSA and LMR were the independent predictive factors for PSM (OR: 2.817; 95% CI, 1.836–4.320, P<0.001; OR: 1.124; 95% CI, 1.018–1.240, P=0.021. Considering pre-, intra-, and postoperative variables, BGS, perineural invasion, seminal vesicle invasion (SVI), pathologic Gleason sum (PGS) combined, were associated with increased risk of PSM in the univariable analysis (P<0.001 for all variables). However, in the multivariable analysis, perineural invasion (OR: 2.672; 95% CI, 1.649–4.330; P<0.001), PGS (OR: 2.52; 95% CI, 1.556–4.082; P<0.001) were independent predictive factors for the incidence of PSM. Finally, LMR was shown to be an independent predictive factor (OR: 0.881; 95% CI, 0.779–0.996; P=0.043) for apical PSMs, with increasing LMR predicting the lower incidence of apex location. And we also found that LMR was an independent factor that predicts multifocal positive margins (OR: 1.179; 95% CI, 1.023–1.358; P=0.023).ConclusionsPreoperative LMR could be used as an independent predictor to predict the incidence of PSMs after RP. And Considering pre-, intra-, and postoperative variables, we also found that preoperative LMR could predict the occurrence of apical and multifocal PSMs.     

Cause-specific mortality of low and selective intermediate-risk prostate cancer patients with active surveillance or watchful waiting

BackgroundActive surveillance or watchful waiting (AS/WW) is increasingly being used as an alternative strategy to radical prostatectomy or radiation therapy for appropriately selected patients with prostate cancer (PCa). However, the prognosis of low-risk and selective intermediate-risk PCa patients after AS/WW is poorly defined. In this study we reviewed the patients registered in the Surveillance, Epidemiology, and End Results (SEER) Program to establish a competing risk nomogram for the prediction of prostate cancer-specific mortality (PCSM).MethodsThe information of patients undergoing AS/WW in the SEER program from 2004 to 2015 was obtained. All patients were ISUP (International Society of Urological Pathology) grade 1 or 2 PCa and also fulfilled the National Comprehensive Cancer Network’s definition of low-risk PCa [prostate specific antigen (PSA) <10 ng/mL and cT2aN0M0 or less)]. A competing risk nomogram was used to analyze the association of tumor characteristics with PCSM and non-PCSM among the PCa patients with AS/WW. All cases were randomly divided into a training cohort and a validation cohort (1:1). A competing risk nomogram was constructed to predict PCSM in PCa patients with AS/WW. The performance of the PCSM nomogram was evaluated using the concordance index (C-index) and calibration curve.ResultsA total of 30,538 PCa patients were identified as low risk or selective intermediate risk with AS/WW. The 10-year cumulative incidence of death from prostate cancer and death from other cause were 2.8% (95% CI: 2.4–3.1%) and 19.3% (95% CI: 17.8–20.5%), respectively. Variables associated with PCSM included age, marital status, PSA, and ISUP grade. The PCSM nomogram had a good performance in both the training and validation cohorts, with a C-index of 0.744 (95% CI: 0.700–0.781, P<0.001) and 0.738 (95% CI: 0.700–0.777, P<0.001), respectively.ConclusionsOverall, the prognosis was favorable for the low- and selective intermediate-risk PCa patients with AS/WW. The competing risk nomogram yielded a good performance in identifying subgroups of patients with a higher risk of PCSM and potential candidates for AS/WW.     

Do androgen-directed therapies improve outcomes in prostate cancer patients undergoing radical prostatectomy? A systematic review and meta-analysis

IntroductionApproximately 50% of patients with non-metastatic prostate cancer are treated with radical prostatectomy (RP). While some men will be cured with surgery alone, a substantial proportion will experience cancer recurrence. Androgen-directed therapy (ADT) is an effective adjuvant therapy for patients treated with prostate radiation. Comparatively, the efficacy of ADT in surgical patients has not been well-studied.MethodsA systematic search of MEDLINE, Embase, and the Cochrane Library from inception to July 2020 was performed. Randomized trials comparing ADT with RP vs. prostatectomy alone in patients with clinically localized prostate cancer were included. Neoadjuvant ADT and adjuvant ADT interventions were assessed separately. The primary outcomes were cancer recurrence-free survival (RFS) and overall survival (OS). Pathological outcomes following neoadjuvant ADT were also evaluated.ResultsFifteen randomized trials met eligibility criteria; 11 evaluated neoadjuvant ADT (n=2322) and four evaluated adjuvant ADT (n=5205). Neoadjuvant ADT (three months of treatment) did not improve RFS (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.74–1.11) or OS (HR 1.22, 95% CI 0.62–2.41). Neoadjuvant ADT significantly decreased the risk of positive surgical margins (relative risk [RR] 0.48, 95% CI 0.41–0.56) and extraprostatic tumor extension (RR 0.75, 95% CI 0.64–0.89). Adjuvant ADT improved RFS (HR 0.65, 95% CI 0.45–0.93) but did not improve OS (HR 1.02, 95% CI 0.84–1.24).ConclusionsNeoadjuvant ADT causes a pathological downstaging of prostate tumors but has not been found to delay cancer recurrence nor extend survival. Few studies have evaluated adjuvant ADT. Trials are needed to determine the benefits and harms of intermediate- or long-term adjuvant ADT for RP patients.     

The risks,degree of malignancy and clinical progression of prostate cancer associated with the MDM2 T309G polymorphism: a meta-analysis

To determine the risk, malignant degree and clinical progression of prostate cancer (PCa) associated with mouse double-minute 2 protein (MDM2) T309G variants, a meta-analysis was performed on all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess these associations in seven studies that included 5151 cases and 1003 controls. In the overall analysis, the 309G allele was significantly associated with a decreased PCa risk (OR=0.85, 95% CI: 0.74–0.97); this was also the case for the homozygous comparison (OR=0.72, 95% CI: 0.55–0.95) and the dominant genetic model (OR=0.79, 95% CI: 0.65–0.96). The 309G allele was also found to be significantly associated with lower degrees of PCa malignancy (OR=0.85, 95% CI: 0.75–0.96) in the overall analysis, as well as in the heterozygous comparison (OR=0.79, 95% CI: 0.65–0.96), homozygous comparison (OR=0.76, 95% CI: 0.58–0.98) and dominant genetic model (OR=0.81, 95% CI: 0.68–0.96). Furthermore, grouping analysis showed that the 309G allele in Caucasians was significantly correlated with a decreased PCa risk (OR=0.77, 95% CI: 0.61–0.96); this was also the case in the homozygous comparison (OR=0.51, 95% CI: 0.31–0.86). The grouping analysis also showed that the 309G variant in Caucasians was significantly associated with a lower degree of PCa malignancy in all of the genetic models. In addition, we found that the 309G variant in Caucasians was significantly associated with a slower PCa clinical progression in all of the genetic models. In summary, our meta-analysis showed that the MDM2 309G variant was significantly associated with a decreased PCa risk, lower malignant degree and slower clinical progression in Caucasians, but there was no obvious association in the Asian population.     

Inflammatory bowel disease and risk of urinary cancers: a systematic review and pooled analysis of population-based studies

BackgroundThe aim of this study is to elucidate the risk of urologic cancers in patients with Crohn’s disease (CD) and ulcerative colitis (UC).MethodsElectronic databases including PubMed, the Cochrane Library, Embase and Web of Science, and manual retrieval were conducted from inception to June 2020. Two reviewers independently searched the above databases and selected the studies using prespecified standardized criteria. The Newcastle-Ottawa Scale was used to assess the risk of bias in the included studies, and this meta-analysis was completed by STATA version 14.2.ResultsA total of 12 cohort studies and 4 case-control studies were included in this meta-analysis. Overall, patients with inflammatory bowel disease (IBD) were at significantly increased risk of renal cancer (RCa) [standardized incidence ratio (SIR): 1.53; 95% confidence interval (CI): 1.25–1.80; I²=42.4%], but not at increased risk of prostate cancer (PCa), bladder cancer (BCa) and male genital cancer. In the subgroup analysis, CD patients had a significantly higher RCa risk (SIR: 1.95; 95% CI: 1.45–2.44; I²=39.9%). Besides, CD patients seemed to be at borderline significantly increased risks of PCa (SIR: 1.07; 95% CI: 0.93–1.20; I²=15.1%) and BCa (SIR:1.19; 95% CI: 0.94–1.44; I²=0%), and UC patients seemed to be at borderline significantly increased risks of RCa (SIR:1.31; 95% CI: 0.94–1.67; I²=48.0%) and PCa (SIR: 1.13; 95% CI: 0.93–1.33; I²=73.5%). Notably, we observed that IBD patients in Eastern countries have significantly increased PCa risk (SIR: 2.66; 95% CI: 1.52–3.81; I²=13.6%), especially for UC patients (SIR: 3.01; 95% CI: 1.75–4.27; I²=0.0%).ConclusionsOur findings indicate that IBD patients with special reference to CD patients increase the risk of RCa. Besides, IBD patients in Asian countries have significantly increased risk of PCa, especially for UC patients. Further studies are warranted to elucidate the potential mechanism of RCa associated with IBD and the differences of the risk of urinary cancers between Eastern and Western countries.     

Region 2 of 8q24 is associated with the risk of aggressive prostate cancer in Caribbean men of African descent from Guadeloupe (French West Indies)

Multiple regions of the genome have been associated with the risk of prostate cancer in Caucasians, particularly including several polymorphisms located at 8q24. Region 2 of 8q24 has been repeatedly found to be associated with the risk of prostate cancer among men of African descent, although one study performed in the Caribbean island of Jamaica did not report this finding. In this study, the single nucleotide polymorphism rs16901979, located in region 2 of 8q24, was genotyped in 498 cases of histologically confirmed prostate cancer and 541 controls from the French Caribbean islands of Guadeloupe, where the population is largely of African descent. The AA genotype and the A allele at rs16901979 were associated with elevated risks of prostate cancer (odds ratios [ORs] = 1.84, 95% confidence interval [95% CI] = 1.26–2.69, P = 0.002 and OR = 1.36, 95% CI = 1.13–1.64, P = 0.001, respectively). Following stratification of the patients by disease aggressiveness, as defined by the Gleason score, the pooled genotypes AC + AA were associated with a higher risk of a Gleason score ≥7 at diagnosis (OR = 1.79, 95% CI = 1.17–2.73, P = 0.007). In summary, the A allele at rs16901979 was associated with the risk of prostate cancer in the Caribbean population of Guadeloupe, confirming its involvement in populations of African descent. Moreover, our study provides the first evidence of an association between this variant and the risk of aggressive prostate cancer.     

Prostate Cancer Risks for Male BRCA1 and BRCA2 Mutation Carriers: A Prospective Cohort Study

BackgroundBRCA1 and BRCA2 mutations have been associated with prostate cancer (PCa) risk but a wide range of risk estimates have been reported that are based on retrospective studies.ObjectiveTo estimate relative and absolute PCa risks associated with BRCA1/2 mutations and to assess risk modification by age, family history, and mutation location.Design, setting, and participantsThis was a prospective cohort study of male BRCA1 (n = 376) and BRCA2 carriers (n = 447) identified in clinical genetics centres in the UK and Ireland (median follow-up 5.9 and 5.3 yr, respectively).Outcome measurements and statistical analysisStandardised incidence/mortality ratios (SIRs/SMRs) relative to population incidences or mortality rates, absolute risks, and hazard ratios (HRs) were estimated using cohort and survival analysis methods.Results and limitationsSixteen BRCA1 and 26 BRCA2 carriers were diagnosed with PCa during follow-up. BRCA2 carriers had an SIR of 4.45 (95% confidence interval [CI] 2.99–6.61) and absolute PCa risk of 27% (95% CI 17–41%) and 60% (95% CI 43–78%) by ages 75 and 85 yr, respectively. For BRCA1 carriers, the overall SIR was 2.35 (95% CI 1.43–3.88); the corresponding SIR at age <65 yr was 3.57 (95% CI 1.68–7.58). However, the BRCA1 SIR varied between 0.74 and 2.83 in sensitivity analyses to assess potential screening effects. PCa risk for BRCA2 carriers increased with family history (HR per affected relative 1.68, 95% CI 0.99–2.85). BRCA2 mutations in the region bounded by positions c.2831 and c.6401 were associated with an SIR of 2.46 (95% CI 1.07–5.64) compared to population incidences, corresponding to lower PCa risk (HR 0.37, 95% CI 0.14–0.96) than for mutations outside the region. BRCA2 carriers had a stronger association with Gleason score ≥7 (SIR 5.07, 95% CI 3.20–8.02) than Gleason score ≤6 PCa (SIR 3.03, 95% CI 1.24–7.44), and a higher risk of death from PCa (SMR 3.85, 95% CI 1.44–10.3). Limitations include potential screening effects for these known mutation carriers; however, the BRCA2 results were robust to multiple sensitivity analyses.ConclusionsThe results substantiate PCa risk patterns indicated by retrospective analyses for BRCA2 carriers, including further evidence of association with aggressive PCa, and give some support for a weaker association in BRCA1 carriers.Patient summaryIn this study we followed unaffected men known to carry mutations in the BRCA1 and BRCA2 genes to investigate whether they are at higher risk of developing prostate cancer compared to the general population. We found that carriers of BRCA2 mutations have a high risk of developing prostate cancer, particularly more aggressive prostate cancer, and that this risk varies by family history of prostate cancer and the location of the mutation within the gene.     

The effect of lowering cholesterol through diet on serum prostate-specific antigen levels: A secondary analysis of clinical trials

ImportanceStatins appear to lower serum prostate-specific antigen (PSA) and improve prostate cancer (PCa) outcomes through cholesterol-dependent and independent mechanisms. While dietary modifications have an established role in serum cholesterol reduction, whether diet-driven cholesterol reductions yield similar PCa benefits to that observed with statins is unclear. We aimed to study the effect of dietdriven cholesterol reduction on serum PSA and estimated-PCa risk.MethodsA total of 291 men from six published randomized controlled trials of dietary interventions were included. Men were aged ≥40 years, free of PCa, and had baseline PSA <10.0 ng/mL. Participants received one of four diets (high-fiber, low-glycemic index, low-glycemic load, or cholesterol-lowering) for 8–24 weeks. The primary outcome evaluated the association between change from baseline low-density lipoprotein cholesterol (LDL-C) and PSA. How cholesterol reduction modified PCa risk was estimated using the Prostate Cancer Prevention Trial (PCPT) risk calculator (limited to age ≥55 years, baseline PSA ≥1.0 ng/mL).ResultsBaseline PSA was 0.90 ng/mL (interquartile range [IQR] 0.55–1.60) and LDL-C was 90 mg/dL (IQR 69–125). In multivariate regression, PSA decreased 1.9% (95% confidence interval [CI] 0.55–3.2, p=0.005) per 10% reduction in LDL-C. This regression was greater in men with baseline PSA ≥2.0 ng/mL (−5.4%, 95% CI 2.2–8.6] per 10% LDL-C reduction, p-interaction=0.001). In men with estimable PCPT risk, statin-comparable LDL-C reductions (≥15%) reduced PSA by 12% (p<0.001) and estimated PCa risk by 6.5% (p=0.005).ConclusionsThis is the first study to show that serum cholesterol reduction through dietary interventions significantly lowered serum PSA and estimated PCa risk. Whether cholesterol-lowering diets improve PCa outcomes warrants investigation.     

A systematic review and meta-analysis of efficacy and safety comparing holmium laser enucleation of the prostate with transurethral resection of the prostate for patients with prostate volume less than 100 mL or 100 g

BackgroundTo assess the efficacy and safety of holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TURP) for patients with prostate volume less than 100 mL or 100 g.MethodsWe searched PubMed, Embase, Cochrane Library and Web of Science from inception to July 2021 to collect randomized controlled trials. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies by using the Cochrane risk of bias tool. Review Manager 5.3 software was used for meta-analysis. We synthesised effect estimates using risk ratios (RR), mean difference (MD), and standardized mean differences (SMD).ResultsA total of eight studies were included, involving 764 patients, 384 patients in the HoLEP group and 380 patients in the TURP group. The meta-analysis showed that the catheterization time (SMD =−1.44; 95% CI: −2.17 to −0.70; P=0.0001), hospital stay (SMD =−1.01; 95% CI: −1.58 to −0.44; P=0.0005), haemoglobin loss (MD =−0.29; 95% CI: −0.52 to −0.07; P=0.01), and transfusion rate (RR =0.16; 95% CI: 0.05–0.49; P=0.001) in the HoLEP group were lower than those in the TURP group. In addition, the 12-month postvoid residual volume (PVR) of the HoLEP group (MD =−9.93 95% CI: −18.59 to −1.27; P=0.02) were superior to the TURP group. Although the operation time of the HoLEP group was longer (MD =17.89; 95% CI: 9.18–26.60; P<0.0001), more tissues were removed (SMD =0.47; 95% CI: 0.10–0.85; P=0.01).DiscussionCompared with TURP, HoLEP has a shorter catheterization time and hospital stay, with more tissue removed, a lower blood transfusion rate and better results in the short-term follow-up after surgery. Therefore, HoLEP has better efficacy and safety in the treatment of small- and medium-sized benign prostatic obstruction. Our results found that HoLEP is also suitable for patients with prostate volume <100 mL/100 g, suggesting that it is necessary to redefine the prostate size that is best for HoLEP. Overall, the certainty of evidence was assessed to be moderate to low due to potential risk of bias and inconsistent outcome indicators in some studies. More data on the efficacy of HoLEP and TURP on small- and medium-sized prostates are needed to determine the optimal prostate volume of HoLEP.     

LncRNA SNHG9 is a prognostic biomarker and correlated with immune infiltrates in prostate cancer

BackgroundExpression of Long non-coding RNA (LncRNA) small nucleolar RNA host gene 9 (SNHG9) is observed in some cancer types, while its role in prostate cancer (PCa) is unclear. We aimed to demonstrate the relationship between SNHG9 and PCa based on The Cancer Genome Atlas (TCGA) database.MethodsKruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate relationships between clinical-pathologic features and SNHG9 expression. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of SNHG9 using area under curve (AUC) score. Kaplan-Meier method and Cox regression analysis were used to evaluate factors contributing to prognosis. Gene set enrichment analysis (GSEA) and immune infiltration analysis were performed to identify the significantly involved functions of SNHG9.ResultsIncreased SNHG9 expression in PCa was associated with N stage (P<0.001), Gleason score (P=0.002), primary therapy outcome (P=0.001), residual tumor (P<0.001) and prostate specific antigen (PSA) (P=0.007). ROC curve suggested the significant diagnostic and prognostic ability of SNHG9 (AUC =0.815). High SNHG9 expression predicted a poorer progression-free survival (PFS) (P=0.002), and SNHG9 expression (HR: 1.776; 95% CI: 1.067–2.955; P=0.027) was independently correlated with PFS in PCa patients. GSEA and immune infiltration analysis showed that SNHG9 expression was correlated with regulating the function of ribosome and some types of immune infiltrating cells.ConclusionsSNHG9 expression was significantly correlated with poor survival and immune infiltrations in PCa, and it may be a promising prognostic biomarker in PCa.     

Carcinogenicity risk associated with tacrolimus use in kidney transplant recipients: a systematic review and meta-analysis

BackgroundCurrently, tacrolimus is the preferred anti-rejection therapy for kidney transplant recipients due to its greater protection against acute rejections compared to cyclosporin A (CsA). Despite the advantages of kidney transplantation, it has been associated with an increased incidence of de novo malignancies. Furthermore, a systematic review in 2005 revealed no statistical difference in tumorigenicity between tacrolimus and CsA. This report provides an up to date systematic review and evaluation of all relevant studies in the literature to determine the risk of malignancy in kidney transplant recipients exposed to tacrolimus.MethodsA systematic literature search was performed using the Medline (PubMed and Ovid), Embase, Clinical Trials, and Cochrane databases (from creation to May 2021). We performed a meta-analysis of 11 studies with 36,985 kidney transplant recipients that compared the tacrolimus group with the control group. Outcomes of this study were incidence of malignancies and skin cancer risk. Risk of Bias was assessed in terms of whether there was random sequence generation, allocation concealment, blinding, completeness of results, selective reporting, etc. This meta-analysis was performed in accordance with PRISMA guidelines.ResultsOf the 11 included studies, 8 were high quality studies, 1 was assessed as medium quality, and 2 were low quality studies. The results showed a significantly increased risk of overall malignancy associated with tacrolimus exposure compared to non-tacrolimus therapy [risk ratio (RR) =1.59; 95% confidence interval (CI): 1.19–2.11; P=0.002], and especially with sirolimus (SRL) (RR =2.58; 95% CI: 1.62–4.09; P<0.0001). The incidence of skin cancer was consistent with the overall study (RR =2.03; 95% CI: 1.25–3.28; P=0.004). However, there was no significant difference in the incidence of tumors between tacrolimus and cyclosporine A treatment (RR =1.12; 95% CI: 0.80–1.56; P=0.52), even in studies with long follow-up periods of more than 3 years.DiscussionThe data demonstrated that patients treated with tacrolimus had a higher risk of carcinogenicity compared to patients treated with SRL. However, patients treated with tacrolimus had a similar incidence of carcinogenicity compared to patients treated with CsA. Further clinical studies are warranted to confirm these findings.     

Impact of 5α-reductase inhibitors on men followed by active surveillance for prostate cancer

Background

In two large randomized controlled trials, 5α-reductase inhibitors (5-ARIs) were shown to prevent prostate cancer. No prior work had shown the effect of 5-ARIs on those already diagnosed with low-risk prostate cancer.

Objective

Our aim was to determine the effect of 5-ARIs on pathologic progression in men on active surveillance.

Design, setting, and participants

We conducted a single-institution retrospective cohort study comparing men taking a 5-ARI versus no 5-ARI while on active surveillance for prostate cancer.

Measurements

Pathologic progression was evaluated and defined as Gleason score >6, maximum core involvement >50%, or more than three cores positive on a follow-up prostate biopsy. Kaplan-Meier analyses were conducted along with multivariable Cox proportional hazard regression modeling for predictors of pathologic progression.

Results and limitations

A total of 288 men on active surveillance met the inclusion criteria. The median follow-up was 38.5 mo (interquartile range: 23.6–59.4) with 93 men (32%) experiencing pathologic progression and 96 men (33%) abandoning active surveillance. Men taking a 5-ARI experienced a lower rate of pathologic progression (18.6% vs 36.7%; p = 0.004) and were less likely to abandon active surveillance (20% vs 37.6%; p = 0.006). On multivariable Cox proportional hazards analysis, lack of 5-ARI use was most strongly associated with pathologic progression (hazard ratio: 2.91; 95% confidence interval, 1.5–5.6). The main study limitation was the retrospective design and variable duration of 5-ARI therapy.

Conclusions

The 5-ARIs were associated with a significantly lower rate of pathologic progression and abandonment of active surveillance.     

Impact of Chronic Kidney Disease on the Prognosis of Transcatheter Aortic Valve Replacement in Patients with Aortic Stenosis: A Meta-Analysis of 133624 Patients

Purpose: The impact of chronic kidney disease (CKD) on the prognosis of transcatheter aortic valve replacement (TAVR) remains unclear. The purpose of this meta-analysis was to assess the impact of CKD and different stages of CKD on prognosis in patients undergoing TAVR.Methods: As of June 2020, we performed a comprehensive literature search on relevant studies using PubMed, Embase, Cochrane Library, and Web of Science. Subsequently, we pooled the risk ratio (RR) of individual studies via random effects to analyze heterogeneity, quality assessment, and publication bias.Results: A total of 20 studies, involving 133624 patients, were eligible for analysis. Patients with CKD had higher all-cause mortality at 30 days (RR: 1.39, 95% confidence interval [CI]: 1.31–1.47, P <0.001), 1 year (RR: 1.36, 95% CI: 1.24–1.49, P <0.001), and 2 years (RR: 1.2, 95% CI: 1.05–1.38, P = 0.009) of follow-up. Moreover, they also had higher acute kidney injury (AKI) (RR: 1.38, 95% CI: 1.16–1.63, P <0.001) and bleeding (RR: 1.33, 95% CI: 1.18–1.50, P <0.001) at 30 days. CKD3 alone also increased all-cause mortality at follow-ups. Risk of all-cause mortality increased with severity of CKD for stages 3, 4, and 5 at follow-up.Conclusion: Patients with CKD are at an increased risk of all-cause mortality, AKI, and bleeding events after TAVR. Moreover, the mortality risk rises with increasing severity of CKD.     

Reprint – Bipolar vs. monopolar transurethral resection of the prostate for lower urinary tract symptoms secondary to benign prostatic obstruction: A Cochrane review

IntroductionThere remains uncertainty regarding the differences in patient outcomes between monopolar transurethral resection of the prostate (MTURP) and bipolar TURP (BTURP) in the management of lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO).MethodsA systematic literature search was carried out up to March 19, 2019. Methods in the Cochrane Handbook were followed. Certainty of evidence (CoE) was assessed using the GRADE approach.ResultsA total of 59 randomized controlled trials (RCTs) with 8924 participants were included. BTURP probably results in little to no difference in International Prostate Symptom Score (IPSS) at 12 months (mean difference −0.24, 95% confidence internal [CI] −0.39–−0.09; participants=2531; RCTs=16; moderate CoE) or health-related quality of life (HRQOL) at 12 months (mean difference −0.12, 95% CI −0.25–0.02; participants=2004, RCTs=11; moderate CoE), compared to MTURP. BTURP probably reduces TUR syndrome (relative risk [RR] 0.17, 95% CI 0.09–0.30; participants= 6,745, RCTs=44; moderate CoE) and blood transfusions (RR 0.42, 95% CI 0.30–0.59; participants=5727, RCTs=38; moderate CoE), compared to MTURP. BTURP may carry similar risk of urinary incontinence at 12 months (RR 0.20, 95% CI 0.01–4.06; participants=751; RCTs=4; low CoE), re-TURP (RR 1.02, 95% CI 0.44–2.40; participants=652, RCTs=6, I²=0%; low CoE) and erectile dysfunction (International Index of Erectile Function [IIEF-5]) at 12 months (mean difference 0.88, 95% CI −0.56–2.32; RCTs=3; moderate CoE), compared to MTURP.ConclusionsBTURP and MTURP probably improve urological symptoms to a similar degree. BTURP probably reduces TUR syndrome and blood transfusion slightly postoperatively. The moderate certainty of evidence available for primary outcomes suggests no need for further RCTs comparing BTURP and MTURP.