Prostate-specific antigen velocity (PSAV) risk count improves the specificity of screening for clinically significant prostate cancer.

Objective: •  To determine whether the prostate-specific antigen velocity (PSAV) risk count (i.e. the number of times PSAV exceeds a specific threshold) could increase the specificity of screening for prostate cancer and potentially life-threatening tumours.

Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG.

Background: In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e.

Delay of surgery in men with low risk prostate cancer.

Purpose: Treatment options for patients with low risk prostate cancer include radical prostatectomy, radiation therapy, and active surveillance. Among patients treated with radical prostatectomy, prior studies have demonstrated significantly higher biochemical progression rates with surgical delays of 6 months or greater. We determined the impact of surgical delay on radical prostatectomy outcomes specifically in low risk patients.

Prostate cancer risk alleles significantly improve disease detection and are associated with aggressive features in patients with a "normal" prostate specific antigen and digital rectal examination.

Background: Several reports suggest that a combination of risk alleles may be associated with prostate cancer (CaP) risk and tumor features. However, their ability to detect CaP and tumor characteristics in patients with a "normal" PSA (<4 ng/ml) and non-suspicious digital rectal examination (DRE) remains to be determined.

Methods: We examined 203 men of European ancestry with clinical stage T1c CaP diagnosed at a "normal" PSA and 611 healthy volunteer controls.

Correlation between serum prostate-specific antigen and cancer volume in prostate glands of different sizes.

Objectives: To further evaluate the relationship of prostate-specific antigen (PSA) with prostate size and tumor volume in a contemporary surgical series. Although early studies showed a strong correlation between PSA and tumor volume, it has been suggested that PSA is no longer a valid marker for prostate cancer and only correlates with prostate size.

Methods: From 2003 to 2009, 1234 men with data on prostate weight and total tumor volume underwent radical prostatectomy by a single surgeon.

External validation of the cancer of the prostate risk assessment (CAPRA) score in a single-surgeon radical prostatectomy series.

Objectives: Prostate cancer clinical staging has significant limitations in the ability to accurately risk-stratify patients for prompt treatment or expectant management. The University of California San Francisco Cancer of the Prostate Risk Assessment (UCSF CAPRA) was recently described as a straightforward staging system that uses clinical variables to generate a score ranging from 0 to 10. Our objective was to perform an external validation of the CAPRA score as a predictor of 5-year progression-free survival (PFS) in a single-surgeon radical retropubic prostatectomy (RRP) series.

Genetic prostate cancer risk assessment: common variants in 9 genomic regions are associated with cumulative risk.

Purpose: Five genetic variants along chromosomes 8q24 and 17q have a cumulative association with prostate cancer risk. Our research group previously reported an association between these variants and clinicopathological characteristics. More recently 4 additional prostate cancer susceptibility variants were identified on chromosomes 2p15, 10q11, 11q13 and Xp11.

Number of prostate cancer risk alleles may identify possibly 'insignificant' disease.

Objective: To determine whether the cumulative effects of five prostate cancer risk alleles (three single-nucleotide polymorphisms [SNPs] on chromosome 8Q24 and two SNPs on chromosome 17a) could help to identify possibly 'insignificant' disease.

Materials And Methods: We genotyped 629 men of European ancestry who underwent radical prostatectomy at our institution between 2002 and 2007. Possibly 'insignificant' CaP was defined using the Ohori criteria (organ-confined, tumour volume <0.

Preoperative prostate specific antigen doubling time is not a useful predictor of biochemical progression after radical prostatectomy.

Purpose: Postoperative prostate specific antigen doubling time may be used as a surrogate for prostate cancer specific mortality in patients with biochemical recurrence after radical prostatectomy. Less is known about the usefulness of preoperative prostate specific antigen doubling time for the initial prediction of prostatectomy outcomes.

Materials And Methods: Preoperative prostate specific antigen doubling time was calculated in 1,208 men from a large prostate cancer screening study who were treated with radical prostatectomy.

[-2]Proenzyme prostate specific antigen is more accurate than total and free prostate specific antigen in differentiating prostate cancer from benign disease in a prospective prostate cancer screening study.

Purpose: Due to the limited specificity of prostate specific antigen for prostate cancer screening, there is an ongoing search for adjunctive biomarkers. Retrospective studies have suggested that an isoform of proenzyme prostate specific antigen called [-2]proenzyme prostate specific antigen may enhance the specificity of prostate specific antigen based screening. We examined the usefulness of this isoform in a prospective prostate cancer screening study.

Treatment outcomes of radical prostatectomy in potential candidates for 3 published active surveillance protocols.

Objectives: To examine the treatment outcomes of men who would have been eligible for active surveillance (AS) but underwent immediate radical retropubic prostatectomy (RRP). AS protocols are designed to spare the potential morbidity of treatment to patients with low-risk prostate cancer (PCa).

Methods: From a prospective RRP database, we evaluated the tumor features and treatment outcomes for men who would have met 1 of 3 published AS criteria: (1) clinically localized disease, Gleason < or = 7, and no significant comorbidities (Patel et al, J Urol.

Can prostate specific antigen velocity thresholds decrease insignificant prostate cancer detection?

Purpose: A controversy of current prostate specific antigen based prostate cancer screening is the over detection of potentially insignificant prostate cancer. Because PSA kinetics were previously linked to prostate cancer specific mortality, we determined whether prostate specific antigen velocity is associated with clinically significant prostate cancer.

Materials And Methods: A total of 1,073 men underwent radical prostatectomy from 1992 to 2008 with data available on prostate specific antigen velocity and tumor volume.

Is statin use associated with prostate cancer aggressiveness?

Objective: To further examine the association between statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) and pathological features in a large group of patients undergoing radical prostatectomy (RP), as epidemiological studies have suggested that statins, in addition to their beneficial cardiovascular effects, might reduce the risk of aggressive prostate cancer.

Patients And Methods: From 2003 to 2009, 1351 men with data on preoperative statin use had RP by one surgeon. The clinical and pathological tumour features were compared between 504 users of statins and 847 who were not users.

Reducing blood loss in open radical retropubic prostatectomy with prophylactic periprostatic sutures.

Objective: To determine whether the placement of small-calibre, rapidly absorbed prophylactic periprostatic sutures before the mobilization of the prostate could reduce blood loss during open retropubic radical prostatectomy (RRP).

Patients And Methods: In 2007, during open RRP, we began placing prophylactic haemostatic sutures of 4-0 and 3-0 plain catgut in the anterior portions of the distal neurovascular bundles (NVBs) and lateral to the proximal NVBs and prostate pedicles before initiating the nerve-sparing dissection and mobilizing the prostate gland. To evaluate whether this reduced intraoperative blood loss, we compared estimated blood loss (EBL), non-autologous transfusion rates, and postoperative haemoglobin (Hb) levels between 100 consecutive patients treated immediately before and 100 consecutive patients treated immediately after the adoption of the prophylactic periprostatic suture technique.

Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility.

We report a prostate cancer genome-wide association follow-on study. We discovered four variants associated with susceptibility to prostate cancer in several European populations: rs10934853[A] (OR = 1.12, P = 2.

Does diabetes mellitus modify the association between 17q12 risk variant and prostate cancer aggressiveness?

Objective: To examine further the relationship between diabetes mellitus (DM), genotype and prostate cancer aggressiveness. Specifically, we sought to evaluate for effect modification between DM, a newly discovered prostate cancer susceptibility locus on chromosome 17q12 (single nucleotide polymorphism rs4430796) and prostate cancer features.

Patients And Methods: In 593 genotyped men treated with radical prostatectomy (RP), we examined RP features stratified by DM and rs4430796 carrier status.

Pathological outcomes associated with the 17q prostate cancer risk variants.

Purpose: Recent studies have identified 2 distinct genetic variants along chromosome 17, including allele T of single nucleotide polymorphism rs4430796 on 17q12 and allele G of single nucleotide polymorphism rs1859962 on 17q24, that have been linked to prostate cancer risk. Less is known about tumor pathological features in carriers of these variants.

Materials And Methods: Genotypes for regions 17q12 and 17q24 were determined in 759 white men with prostate cancer and compared to those in 790 healthy control volunteers using logistic regression.

Characteristics of prostate cancers detected at prostate specific antigen levels less than 2.5 ng/ml.

Purpose: The Prostate Cancer Prevention Trial reported that 15% of men with a prostate specific antigen less than 4 ng/ml and a normal digital rectal examination have biopsy detectable prostate cancer. However, limited published data describe the tumor features of prostate cancer detected at low prostate specific antigen levels (less than 2.5 ng/ml).

Outcomes of radical prostatectomy for patients with clinical stage T1a and T1b disease.

Objective: To compare the outcomes between patients with stage T1a/b with those of patients with T1c cancer of the prostate treated with radical retropubic prostatectomy (RRP), as the appropriate management of clinical stage T1a/b prostate cancer is subject to debate; although many patients are managed expectantly, some have adverse pathological features suggesting that more active treatment might be beneficial.

Patients And Methods: From 1983 to 2003, 3478 men had RRP by one surgeon. From this group, we retrospectively identified 29 men with clinical stage T1a and 83 with clinical stage T1b disease.

Sequence variants at the TERT-CLPTM1L locus associate with many cancer types.

The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.

Prostate specific antigen assay standardization bias could affect clinical decision making.

Purpose: Although prostate specific antigen is widely used to detect and manage prostate cancer, many patients and physicians are unaware of which prostate specific antigen assay is being used. Most commercial prostate specific antigen assays are standardized to the WHO 90:10 standard or aligned with the original Hybritech assay with potentially disparate results.

Materials And Methods: A total of 1,916 men participated in a prostate cancer screening study in 2007.

A genome-wide linkage study of GAW15 gene expression data.

Background: Recently, gene expression levels have been shown to demonstrate familial aggregation, suggesting a direct role of heritable DNA variation. We studied the gene expression levels in lymphoblastoid cells of the Centre d'Etude du Polymorphisme Humain Utah families made available to Genetic Analysis Workshop 15 (GAW15), using genome-wide linkage analyses.

Methods: Heritability was estimated for the expression levels of each individual phenotype.

Summary of Genetic Analysis Workshop 15: Group 9 linkage analysis of the CEPH expression data.

Group 9 participants carried out linkage analysis of the Centre d'Etude de Polymorphism Humain (CEPH) expression data, using strategies that ranged from focused investigation of a small number of traits to full genome scans of all available traits. Results from five key areas encompass the most important results within and across the 17 participating groups. First, both extensive genetic heterogeneity and poor predictability of mapping results based on heritability have key implications for study design.

A genome-wide scan of loci linked to serum adiponectin in two populations of African descent.

Objective: The objectives were to identify quantitative trait loci linked to serum adiponectin concentration and to estimate heritability in two populations of African descent.

Research Methods And Procedures: We conducted a genome scan for serum adiponectin concentration in two populations of African descent. Genome-wide microsatelitte markers were typed in an African-American population consisting of 203 families from the Chicago area and in a Nigerian Yoruba population consisting of 146 families.

An updated meta-analysis of genome scans for hypertension and blood pressure in the NHLBI Family Blood Pressure Program (FBPP).

A meta-analysis of the results from a multicenter genome-wide linkage study for hypertension and blood pressure (BP) based on an initial sample of 6,245 individuals was published in 2003. We report here a combined linkage analysis of hypertension and BP using the complete Family Blood Pressure Program (FBPP) dataset, which includes a total of 12,028 genotyped individuals. Genome-wide linkage analyses for hypertension and BP were first performed in each of the studied ethnic group within each network and the results were combined with a meta-analysis using a modified Fisher's method of combining P values.