MATERIALS AND METHODS: This was an age-matched case-control study of US occurrence after PK-TURP. Retrospective data were collected from the hospital records of patients who had a minimum of 36 months of follow-up information. Among the data collected for analysis were prostate-specific antigen level, estimated prostate weight, the amount of prostate resected, operative time, history of urinary tract infection, previous transurethral resection of the prostate, and whether the PK-TURP was combined with other endourological procedures. The resection rate was calculated from the collected data. Univariate and multivariate analyses were performed to identify clinical and surgical risk factors related to US formation.
RESULTS: A total of 373 patients underwent PK-TURP between 2003 and 2009. There were 13 cases of US (3.5%), and most of them (10 of 13, 76.9%) presented within 24 months of surgery. Most of the US cases (11 of 13, 84.6%) occurred at the bulbar urethra. Multivariable logistic regression analyses identified slow resection rate as the only risk factor significantly associated with US occurrence.
CONCLUSIONS: The US rate of 3.5% after PK-TURP in this study is comparable to contemporary series. A slow resection rate seems to be related to US occurrence. This should be confirmed by further studies; meanwhile, we must be mindful of this possibility when operating with the PK-TURP system.
PATIENTS AND METHODS: A total of 120 men, aged 40-70 years, with TD (serum total testosterone [TT] ≤ 12 nmol/L) were randomised to receive either i.m. TU (1000 mg) or placebo. In all, 58 and 56 men in the placebo and treatment arm, respectively, completed the study. Participants were seen six times in the 48-week period and the following data were collected: physical examination results, haemoglobin, haematocrit, TT, lipid profile, fasting blood glucose, sex hormone-binding globulin, liver function test, prostate- specific antigen (PSA) and adverse events.
RESULTS: The mean (sd) age of the participants was 53.4 (7.6) years. A significant increase in serum TT (P < 0.001), PSA (P = 0.010), haematocrit (P < 0.001), haemoglobin (P < 0.001) and total bilirubin (P = 0.001) were seen in the treatment arm over the 48-week period. Two men in the placebo arm and one man in the treatment arm developed myocardial infarction. Common adverse events observed in the treatment arm included itching/swelling/pain at the site of injection, flushing and acne. Overall, TU injections were well tolerated.
CONCLUSIONS: TU significantly increases serum testosterone in men with TD. PSA, haemoglobin and haematocrit were significantly elevated but were within clinically safe limits. There was no significant adverse reaction that led to the cessation of treatment.
MATERIALS AND METHODS: From March 2015 to August 2016, all men consecutively undergoing transrectal ultrasound (TRUS)-guided prostate biopsy with total PSA values ≤ 20ng/ ml were recruited. Blood samples were taken immediately before undergoing prostate biopsy. The performance of total PSA, %fPSA, %p2PSA and PHI in determining the presence of PCa on prostate biopsy were compared.
RESULTS: PCa was diagnosed in 25 of 84 patients (29.7%). %p2PSA and PHI values were significantly higher (p<0.05) in patients with PCa than those without PCa. The areas under the receiver operating characteristic curves for total PSA, %fPSA, %p2PSA and PHI were 0.558, 0.560, 0.734 and 0.746, respectively. At 90% sensitivity, the specificity of PHI (42.4%) was five times better than total PSA (8.5%) and two times better than %fPSA (20.3%). By utilising PHI cut-off >22.52, 27 of 84 (32.1%) patients could have avoided undergoing biopsy.
CONCLUSION: Findings of our study support the potential clinical effectiveness of PHI in predicting PCa in a wider concentration range of total PSA up to 20ng/ml.
MATERIALS AND METHODS: This retrospective cross sectional study looked at prostate cancer patients seen in the Urology Departments in 2 tertiary centres over the 11 year period starting from January 2000 to May 2011. Patient demographic data, levels of PSA at diagnosis, Gleason score for the biopsy core, T-staging as well as the lymph node status were recorded and analysed.
RESULTS: 258 men were included. The mean age of those 90 men (34.9%) with bone metastasis was 69.2 ± 7.3 years. Logistic regression found that PSA level (P=0.000) at diagnosis and patient's nodal-stage (P=0.02) were the only two independent variables able to predict the probability of bone metastasis among the newly diagnosed prostate cancer patients. Among those with a low PSA level less than 20 ng/ml, and less than 10 ng/ml, bone metastasis were detected in 10.3% (12 out of 117) and 9.7% (7 out of 72), respectively. However, by combining PSA level of 10 ng/ml or lower, and nodal negative as the two criteria to predict negative bone scan, a relatively high negative predictive value of 93.8% was obtained. The probability of bone metastasis in prostate cancer can be calculated with this formula: -1.069+0.007(PSA value, ng/ml) +1.021(Nodal status, 0 or 1)=x Probability of bone metastasis=2.718 x/1+2.718 x.
CONCLUSION: Newly diagnosed prostate cancer patients with a PSA level of 10 ng/ml or lower and negative nodes have a very low risk of bone metastasis (negative predictive value 93.8%) and therefore bone scans may not be necessary.
METHODS: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.
RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.
CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.
IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
Methods: In this work, we reported a colorimetric method for clinical detection of PSA using gold nanoparticles (AuNPs) as the reporters. The method is based on ascorbic acid (AA)-induced in situ formation of AuNPs and Cu2+-catalyzed oxidation of AA. Specifically, HAuCl4 can be reduced into AuNPs by AA; Cu2+ ion can catalyze the oxidation of AA by O2 to inhibit the formation of AuNPs. In the presence of the PSA-specific peptide (DAHSSKLQLAPP)-modified gold-coated magnetic microbeads (MMBs; denoted as DAHSSKLQLAPP-MMBs), complexation of Cu2+ by the MMBs through the DAH-Cu2+ interaction depressed the catalyzed oxidation of AA and thus allowed for the formation of red AuNPs. However, once the peptide immobilized on the MMB surface was cleaved by PSA, the DAHSSKLQ segment would be released. The resultant LAPP fragment remaining on the MMB surface could not sequestrate Cu2+ to depress its catalytic activity toward AA oxidation. Consequently, no or less AuNPs were generated.
Results: The linear range for PSA detection was found to be 0~0.8 ng/mL with a detection limit of 0.02 ng/mL. Because of the separation of cleavage step and measurement step, the interference of matrix components in biological samples was avoided.
Conclusion: The high extinction coefficient of AuNPs facilitates the colorimetric analysis of PSA in serum samples. This work is helpful for designing of other protease biosensors by matching specific peptide substrates.
OBJECTIVE: To report the first year's screening results for all men at enrollment in the study.
DESIGN, SETTING AND PARTICIPANTS: We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrollment, and those men with PSA >3 ng/ml were offered prostate biopsy.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types.
RESULTS AND LIMITATIONS: We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%-double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups.
CONCLUSIONS: The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease.
PATIENT SUMMARY: In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment.
OBJECTIVE: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status.
DESIGN, SETTING, AND PARTICIPANTS: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians.
RESULTS AND LIMITATIONS: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65).
CONCLUSIONS: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.
PATIENT SUMMARY: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.