The TransFORmation of IndiGEnous PrimAry HEAlthcare Delivery (FORGE AHEAD): economic analysis.

BACKGROUND: Indigenous populations have increased risk of developing diabetes and experience poorer treatment outcomes than the general population. The FORGE AHEAD program partnered with First Nations communities across Canada to improve access to resources by developing community-driven primary healthcare models. METHODS: This was an economic assessment of FORGE AHEAD using a payer perspective. Costs of diabetes management and complications during the 18-month intervention were compared to the costs prior to intervention implementation. Cost-effectiveness of the program assessed incremental differences in cost and number of resources utilization events (pre and post). Primary outcome was all-cause hospitalizations. Secondary outcomes were specialist visits, clinic visits and community resource use. Data were obtained from a diabetes registry and published literature. Costs are expressed in 2023 Can$. RESULTS: Study population was ~ 60.5 years old; 57.2% female; median duration of diabetes of 8 years; 87.5% residing in non-isolated communities; 75% residing in communities < 5000 members. Total cost of implementation was $1,221,413.60 and cost/person $27.89. There was increase in the number and cost of hospitalizations visits from 8/$68,765.85 (pre period) to 243/$2,735,612.37. Specialist visits, clinic visits and community resource use followed this trend. CONCLUSION: Considering the low cost of intervention and increased care access, FORGE AHEAD represents a successful community-driven partnership resulting in improved access to resources.

Clinical Impact of Cardiac MRI T1 and T2 Parametric Mapping in Patients with Suspected Cardiomyopathy.

Background There are limited data on the incremental value of parametric mapping compared with core cardiac MRI protocols for suspected cardiomyopathy in routine clinical practice. Purpose To evaluate the impact of cardiac MRI T1 and T2 mapping in routine clinical practice with respect to diagnostic accuracy, reader diagnostic confidence, and downstream cardiac imaging utilization. Materials and Methods In this retrospective single-center study, consecutive clinical cardiac MRI scans obtained with and without T1 and T2 mapping for evaluation of suspected cardiomyopathy between January 2017 and October 2019 were evaluated. Diagnostic accuracy and reader diagnostic confidence were evaluated in a random subset. Downstream cardiac imaging utilization was analyzed in patients with a minimum of 1 year of clinical follow-up ending before January 2020. Results A total of 1876 patients (mean age, 51 years ± 17 [SD]; 1113 men) were evaluated. Of these, 751 (40%) underwent cardiac MRI with the core protocol and 1125 (60%) with the core protocol plus T1 and T2 mapping. In the mapping group, T1 and T2 were high in 280 (25%) and 47 patients (4%), respectively. In the subset evaluated for diagnostic utility (n = 450), the addition of T1 and T2 maps to the core protocol resulted in an improvement in reader diagnostic confidence in 174 patients (39%). Diagnostic sensitivity was higher with the core protocol plus mapping compared with the core protocol alone for myocarditis (89% [31 of 35 patients] vs 69% [24 of 35]; P = .008), Fabry disease (93% [13 of 14 patients] vs 50% [seven of 14]; P = .01), and amyloidosis (100% [16 of 16 patients] vs 63% [10 of 16]; P = .01). In the subset evaluated for downstream imaging utilization (n = 903), 47% of patients with mapping had at least one subsequent cardiac imaging test compared with 55% of patients without mapping (P = .01). Conclusion In patients with suspected cardiomyopathy, cardiac MRI with T1 and T2 mapping had high diagnostic utility and was associated with lower downstream cardiac imaging utilization. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Jerosch-Herold and Coelho-Filho in this issue.

A multi-level qualitative analysis of Telehomecare in Ontario: challenges and opportunities.

BACKGROUND: Despite research demonstrating the potential effectiveness of Telehomecare for people with Chronic Obstructive Pulmonary Disease and Heart Failure, broad-scale comprehensive evaluations are lacking. This article discusses the qualitative component of a mixed-method program evaluation of Telehomecare in Ontario, Canada. The objective of the qualitative component was to explore the multi-level factors and processes which facilitate or impede the implementation and adoption of the program across three regions where it was first implemented. METHODS: The study employs a multi-level framework as a conceptual guide to explore the facilitators and barriers to Telehomecare implementation and adoption across five levels: technology, patients, providers, organizations, and structures. In-depth semi-structured interviews and ethnographic observations with program stakeholders, as well as a Telehomecare document review were used to elicit key themes. Study participants (n = 89) included patients and/or informal caregivers (n = 39), health care providers (n = 23), technicians (n = 2), administrators (n = 12), and decision makers (n = 13) across three different Local Health Integration Networks in Ontario. RESULTS: Key facilitators to Telehomecare implementation and adoption at each level of the multi-level framework included: user-friendliness of Telehomecare technology, patient motivation to participate in the program, support for Telehomecare providers, the integration of Telehomecare into broader health service provision, and comprehensive program evaluation. Key barriers included: access-related issues to using the technology, patient language (if not English or French), Telehomecare provider time limitations, gaps in health care provision for patients, and structural barriers to patient participation related to geography and social location. CONCLUSIONS: Though Telehomecare has the potential to positively impact patient lives and strengthen models of health care provision, a number of key challenges remain. As such, further implementation and expansion of Telehomecare must involve continuous assessments of what is working and not working with all stakeholders. Increased dialogue, evaluation, and knowledge translation within and across regions to understand the contextual factors influencing Telehomecare implementation and adoption is required. This can inform decision-making that better reflects and addresses the needs of all program stakeholders.

The EvalUation of goal-diRected activities to prOmote well-beIng and heAlth (EUROIA) scale: Psychometric evaluation with Confirmatory Factor Analysis.

OBJECTIVES: While state-based models of health-related quality of life (HRQL) are well-established in providing clinically relevant descriptions of HRQL status, they do not provide information on how to maintain or improve HRQL. The EvalUation of goal-diRected activities to prOmote well-beIng and heAlth (EUROIA), rooted in a novel process-based model of HRQL, measures goal-directed activities that are self-reported to promote HRQL as part of an individual's process of adapting to dynamic changes in health status. Our objectives were to condense and summarize the psychometric properties of the EUROIA by (i) defining and confirming its factor structure, (ii) evaluating its construct validity, and (iii) examining its internal consistency. METHODS: Principal component analysis was performed on the 18-item EUROIA to explore the underlying factor structure and condense the scale. Confirmatory factor analysis was conducted on the revised 14-item, 4-factor structure EUROIA instrument to evaluate the model fit. Data was obtained from adult participants with a diagnosis of chronic heart failure or advanced chronic kidney disease from 3 hospitals in Toronto, Canada. RESULTS: The revised 14-item EUROIA demonstrated 4 dimensions-Social Affiliation, fulfillment of Social Roles and Responsibilities, Self-Affirmation, and Eudaimonic Well-being-with a Cronbach's alpha of 0.83, representing good internal consistency. Our confirmatory factor analysis final model achieved good overall model fit: (χ2 / df = 1.80; Tucker-Lewis index = 0.90; comparative fit index = 0.93; standardized root-mean-square residual = 0.06; root-mean-square error of approximation = 0.06). All items exhibited a factor loading greater than λ > 0.4 and p < 0.001. CONCLUSION: The EUROIA holds clinical potential in its ability to provide informed feedback to patients on how they might maintain or modify their use of goal-directed activities to maintain and optimize perceived well-being.

Chip-based nanostructured sensors enable accurate identification and classification of circulating tumor cells in prostate cancer patient blood samples.

The identification and analysis of circulating tumor cells (CTCs) is an important goal for the development of noninvasive cancer diagnosis. Here we describe a chip-based method using nanostructured microelectrodes and electrochemical readout that confirms the identity of isolated CTCs and successfully interrogates them for specific biomarkers. We successfully analyze and classify prostate tumor cells, first in cultured cells, and ultimately in a pilot study involving blood samples from 16 prostate cancer patients as well as additional healthy controls. In all cases, and for all biomarkers investigated, the novel chip-based assay produced results that agreed with polymerase chain reaction (PCR). The approach developed has a simple workflow and scalable multiplexing, which makes it ideal for further studies of CTC biomarkers.

Increasing hospital admission rates for urological complications after transrectal ultrasound guided prostate biopsy.

PURPOSE: Transrectal ultrasound guided prostate biopsy is widely used to confirm the diagnosis of prostate cancer. The technique has been associated with significant morbidity in a small proportion of patients. MATERIALS AND METHODS: We conducted a population based study of 75,190 men who underwent a transrectal ultrasound guided biopsy in Ontario, Canada, between 1996 and 2005. We used hospital and cancer registry administrative databases to estimate the rates of hospital admission and mortality due to urological complications associated with the procedure. RESULTS: Of the 75,190 men who underwent transrectal ultrasound biopsy 33,508 (44.6%) were diagnosed with prostate cancer and 41,682 (55.4%) did not have prostate cancer. The hospital admission rate for urological complications within 30 days of the procedure for men without cancer was 1.9% (781/41,482). The 30-day hospital admission rate increased from 1.0% in 1996 to 4.1% in 2005 (p for trend <0.0001). The majority of hospital admissions (72%) were for infection related reasons. The probability of being admitted to hospital within 30 days of having the procedure increased 4-fold between 1996 and 2005 (OR 3.7, 95% CI 2.0-7.0, p <0.0001). The overall 30-day mortality rate was 0.09% but did not change during the study period. CONCLUSIONS: The hospital admission rates for complications following transrectal ultrasound guided prostate biopsy have increased dramatically during the last 10 years primarily due to an increasing rate of infection related complications.

Protein-coding and microRNA biomarkers of recurrence of prostate cancer following radical prostatectomy.

An important challenge in prostate cancer research is to develop effective predictors of tumor recurrence following surgery to determine whether immediate adjuvant therapy is warranted. To identify biomarkers predictive of biochemical recurrence, we isolated the RNA from 70 formalin-fixed, paraffin-embedded radical prostatectomy specimens with known long-term outcomes to perform DASL expression profiling with a custom panel that we designed of 522 prostate cancer-relevant genes. We identified a panel of 10 protein-coding genes and two miRNA genes (RAD23B, FBP1, TNFRSF1A, CCNG2, NOTCH3, ETV1, BID, SIM2, LETMD1, ANXA1, miR-519d, and miR-647) that could be used to separate patients with and without biochemical recurrence (P < 0.001), as well as for the subset of 42 Gleason score 7 patients (P < 0.001). We performed an independent validation analysis on 40 samples and found that the biomarker panel was also significant at prediction of biochemical recurrence for all cases (P = 0.013) and for a subset of 19 Gleason score 7 cases (P = 0.010), both of which were adjusted for relevant clinical information including T-stage, prostate-specific antigen, and Gleason score. Importantly, these biomarkers could significantly predict clinical recurrence for Gleason score 7 patients. These biomarkers may increase the accuracy of prognostication following radical prostatectomy using formalin-fixed specimens.

Population based study of long-term rates of surgery for urinary incontinence after radical prostatectomy for prostate cancer.

PURPOSE: Urinary incontinence can be a significant complication of radical prostatectomy. It can be treated with post-prostatectomy surgical procedures. The long-term rate of patients who undergo these surgeries, including artificial urinary sphincter or urethral sling insertion, is not well described. We examined the long-term rate of post-prostatectomy incontinence surgery and factors influencing it. MATERIALS AND METHODS: We performed a population based study of 25,346 men who underwent radical prostatectomy for prostate cancer in Ontario, Canada between 1993 and 2006. We used hospital and cancer registry administrative data to identify patients from this cohort who were later treated with surgery for urinary incontinence. RESULTS: Of the 25,346 patients 703 (2.8%) underwent artificial urinary sphincter insertion and 282 (1.1%) underwent urethral sling placement a median of 2.9 years after prostatectomy. The probability of an artificial urinary sphincter/sling procedure increased with time from prostatectomy. Cumulative 5, 10 and 15-year Kaplan-Meier rates of an artificial urinary sphincter/sling procedure were 2.6% (95% CI 2.4-2.8), 3.8% (95% CI 3.6-4.1) and 4.8% (95% CI 4.4-5.3), respectively. Factors predicting surgery for incontinence were patient age at radical prostatectomy (HR 1.24 per decade, 95% CI 1.11-1.38, p = 0.0002), radiotherapy after surgery (HR 1.61, 95% CI 1.36-1.90, p <0.0001) and surgeon volume (49 or greater prostatectomies per year) (HR 0.59, 95% CI 0.46-0.77, p <0.0001). CONCLUSIONS: Of patients who undergo radical prostatectomy 5% are expected to be treated with surgery for urinary incontinence during a 15-year period. Increasing patient age, radiation treatment and low surgeon volume are associated with significantly higher risk.

Impact of Intersecting Systems of Oppression on Diabetic Retinopathy Screening Among Those Who Identify as Women of Low Socioeconomic Status: Protocol for a Convergent Mixed Methods Study.

BACKGROUND: By 2025, 5 million Canadians will be diagnosed with diabetes, and women from lower socioeconomic groups will likely account for most new diagnoses. Diabetic retinopathy is a primary vision complication of diabetes and a leading cause of blindness among adults, with 26% prevalence among women. Tele-retina is a branch of telemedicine that delivers eye care remotely. Screening for diabetic retinopathy has great potential to reduce the incidence of blindness, yet there is an adverse association among screening, income, and gender. OBJECTIVE: We aim to explore gender disparity in the provision of tele-retina program services for diabetic retinopathy screening in a cohort of women of low socioeconomic status (SES) receiving services in South Riverdale Community Health Centre (SRCHC) between 2014 and 2019. METHODS: Using a convergent mixed methods design, we want to understand patients', providers', administrators', and decision makers' perceptions of the facilitators and barriers associated with the implementation and adoption of tele-retina. Multivariate logistic regression will be utilized to assess the association among client characteristics, referral source, and diabetic retinopathy screening. Guided by a grounded theory approach, systematic coding of data and thematic analysis will be utilized to identify key facilitators and barriers to the implementation and adoption of tele-retina. RESULTS: For the quantitative component, we anticipate a cohort of 2500 patients, and we expect to collect data on the overall patterns of tele-retina program use, including descriptions of program utilization rates (such as data on received and completed diabetic retinopathy screening referrals) along the landscape of patient populations receiving these services. For the qualitative component, we plan to interview up to 21 patients and 14 providers, administrators, and decision makers, and to conduct up to 14 hours of observations alongside review of relevant documents. The interview guide is being developed in collaboration with our patient partners. Through the use of mixed methods research, the inquiry will be approached from different perspectives. Mixed methods will guide us in combining the rich subjective insights on complex realities from qualitative inquiry with the standard generalizable data that will be generated through quantitative research. The study is under review by the University Health Network Research Ethics Board (19-5628). We expect to begin recruitment in winter 2021. CONCLUSIONS: In Ontario, the screening rate for diabetic retinopathy among low income groups remains below 65%. Understanding the facilitators and barriers to diabetic retinopathy screening may be a prerequisite in the development of a successful screening program. This study is the first Ontario study to focus on diabetic retinopathy screening practices in women of low SES, with the aim to improve their health outcomes and revolutionize access to quality care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/23492.

Mortality in patients with cardiogenic shock supported with VA ECMO: A systematic review and meta-analysis evaluating the impact of etiology on 29,289 patients.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is associated with variable outcomes. In this meta-analysis, we evaluated the mortality after VA ECMO across multiple etiologies of cardiogenic shock (CS). METHODS: In June 2019, we performed a systematic search selecting observational studies with ≥10 adult patients reporting on short-term mortality (30-day or mortality at discharge) after initiation of VA ECMO by CS etiology published after 2009. We performed meta-analyses using random effect models and used metaregression to evaluate mortality across CS etiology. RESULTS: We included 306 studies (29,289 patients): 25 studies on after heart transplantation (HTx) (771 patients), 13 on myocarditis (906 patients), 33 on decompensated heart failure (HF) (3,567 patients), 64 on after cardiotomy shock (8,231 patients), 10 on pulmonary embolism (PE) (221 patients), 80 on acute myocardial infarction (AMI) (7,774 patients), and 113 on after cardiac arrest [CA] (7,814 patients). With moderate certainty on effect estimates, we observed significantly different mortality estimates for various etiologies (p < 0.001), which is not explained by differences in age and sex across studies: 35% (95% CI: 29-42) for after HTx, 40% (95% CI: 33-46) for myocarditis, 53% (95% CI: 46-59) for HF, 52% (95% CI: 38-66) for PE, 59% (95% CI: 56-63) for cardiotomy, 60% (95% CI: 57-64) for AMI, 64% (95% CI: 59-69) for post‒in-hospital CA, and 76% (95% CI: 69-82) for post-out‒of-hospital CA. Univariable metaregression showed that variation in mortality estimates within etiology group was partially explained by population age, proportion of females, left ventricle venting, and CA. CONCLUSIONS: Using an overall estimate of mortality for patients with CS requiring VA ECMO is inadequate given the differential outcomes by etiology. To further refine patient selection and management to improve outcomes, additional studies evaluating patient characteristics impacting outcomes by specific CS etiology are needed.

Increasing hospital admission rates for urological complications after transrectal ultrasound guided prostate biopsy.

PURPOSE: Transrectal ultrasound guided prostate biopsy is widely used to confirm the diagnosis of prostate cancer. The technique has been associated with significant morbidity in a small proportion of patients. MATERIALS AND METHODS: We conducted a population based study of 75,190 men who underwent a transrectal ultrasound guided biopsy in Ontario, Canada, between 1996 and 2005. We used hospital and cancer registry administrative databases to estimate the rates of hospital admission and mortality due to urological complications associated with the procedure. RESULTS: Of the 75,190 men who underwent transrectal ultrasound biopsy 33,508 (44.6%) were diagnosed with prostate cancer and 41,682 (55.4%) did not have prostate cancer. The hospital admission rate for urological complications within 30 days of the procedure for men without cancer was 1.9% (781/41,482). The 30-day hospital admission rate increased from 1.0% in 1996 to 4.1% in 2005 (p for trend <0.0001). The majority of hospital admissions (72%) were for infection related reasons. The probability of being admitted to hospital within 30 days of having the procedure increased 4-fold between 1996 and 2005 (OR 3.7, 95% CI 2.0-7.0, p <0.0001). The overall 30-day mortality rate was 0.09% but did not change during the study period. CONCLUSIONS: The hospital admission rates for complications following transrectal ultrasound guided prostate biopsy have increased dramatically during the last 10 years primarily due to an increasing rate of infection related complications.

Utility of incorporating genetic variants for the early detection of prostate cancer.

PURPOSE: Several single nucleotide polymorphisms (SNP) have been associated with the risk of prostate cancer. The clinical utility of using SNPs in the early detection of prostate cancer has not been evaluated. EXPERIMENTAL DESIGN: We examined a panel of 25 SNPs from candidate genes and chromosomal regions in 3,004 unselected men who were screened for prostate cancer using serum prostate-specific antigen (PSA) and digital rectal examination. All underwent a prostate biopsy. We evaluated the ability of these SNPs to help predict the presence of prostate cancer at biopsy. RESULTS: Of the 3,004 patients, 1,389 (46.2%) were found to have prostate cancer. Fifteen of the 25 SNPs studied were significantly associated with prostate cancer (P=0.02-7x10(-8)). We selected a combination of 4 SNPs with the best predictive value for further study. After adjusting for other predictive factors, the odds ratio for patients with all four of the variant genotypes compared with men with no variant genotype was 5.1 (95% confidence interval, 1.6-16.5; P=0.006). When incorporated into a nomogram, genotype status contributed more significantly than PSA, family history, ethnicity, urinary symptoms, and digital rectal examination (area under the curve=0.74). The positive predictive value of the PSA test ranged from 42% to 94% depending on the number of variant genotypes carried (P=1x10(-15)). CONCLUSIONS: SNP genotyping can be used in a clinical setting for the early detection of prostate cancer in a nomogram approach and by improving the positive predictive value of the PSA test.

Tele-retina screening of diabetic retinopathy among at-risk populations: an economic analysis.

OBJECTIVES: To assess the cost-effectiveness of the pilot Toronto tele-retina screening program in comparison with existing standard of care (SOC) diabetic retinopathy (DR) screening for patients with diabetes mellitus and in a simulated Pan-Ontarian cohort. METHODS: Decision trees were constructed to compare tele-retina to SOC in the pilot and Pan-Ontarian cohort. Cost-effectiveness was assessed as cost per case detected (true-positive) and cost per case correctly diagnosed (true-positive and true-negative results). RESULTS: Pilot program screening costs were $95.77 and $137.56 for tele-retina and SOC, respectively. In the base-case analysis, cost per case correctly detected was $379.06 with tele-retina and $985.56 with SOC, and the cost per case correctly diagnosed was $109.29 and $315.22, respectively. In the sensitivity analysis, cost per case correctly detected was $467.29 with tele-retina and $894.93 with SOC, and the cost per case correctly diagnosed was $136.88 and $250.35, respectively. Pan-Ontarian screening costs were $57.58 and $137.56 for tele-retina and SOC, respectively. The cost per case correctly detected was $281.10 with tele-retina and $982.00 with SOC, and the cost per case correctly diagnosed was $82.21 and $314.14, respectively. For both pilot and Pan-Ontarian sensitivity analyses, tele-retina remained the dominant strategy (ICER <0). CONCLUSIONS: Findings from this study suggest that tele-retina is a more cost-effective means of screening for diabetic retinopathy than the SOC in urban and rural underscreened communities. Subsequent economic studies should focus on evaluations that consider the impact of tele-retina on the prevention of severe vision loss in underscreened urban and rural communities.

A Prospective Mixed-Methods Study of Decision-Making on Surgery or Active Surveillance for Low-Risk Papillary Thyroid Cancer.

Background: Active surveillance (AS) of small, low-risk papillary thyroid cancers (PTCs) is increasingly being considered. There is limited understanding of why individuals with low-risk PTC may choose AS over traditional surgical management. Methods: We present a mixed-methods analysis of a prospective observational real-life decision-making study regarding the choice of thyroidectomy or AS for management of localized, low-risk PTCs <2 cm in maximum diameter (NCT03271892). Patients were provided standardized medical information and were interviewed after making their decision (which dictated disease management). We evaluated patients' levels of decision-self efficacy (confidence in medical decision-making ability) at the time information was presented and their level of decision satisfaction after finalizing their decision (using standardized questionnaires). We asked patients to explain the reason for their choice and qualitatively analyzed the results. Results: We enrolled 74 women and 26 men of mean age 52.4 years, with a mean PTC size of 11.0 mm (interquartile range 9.0, 14.0 mm). Seventy-one patients (71.0% [95% confidence interval 60.9-79.4%]) chose AS over surgery. Ninety-four percent (94/100) of participants independently made their own disease management choice; the rest shared the decision with their physician. Participants had a high baseline level of decision self-efficacy (mean 94.3, standard deviation 9.6 on a 100-point scale). Almost all (98%, 98/100) participants reported high decision satisfaction. Factors reported by patients as influencing their decision included the following: perceived risk of thyroidectomy or the cancer, family considerations, treatment timing in the context of life circumstances, and trust in health care providers. Conclusions: In this Canadian study, ∼7 out of 10 patients with small, low-risk PTC, who were offered the choice of AS or surgery, chose AS. Personal perceptions about cancer or thyroidectomy, contextual factors, family considerations, and trust in health care providers strongly influenced patients' disease management choices.

Global transcriptome analysis of formalin-fixed prostate cancer specimens identifies biomarkers of disease recurrence.

Prostate cancer remains the second leading cause of cancer death in American men and there is an unmet need for biomarkers to identify patients with aggressive disease. In an effort to identify biomarkers of recurrence, we performed global RNA sequencing on 106 formalin-fixed, paraffin-embedded prostatectomy samples from 100 patients at three independent sites, defining a 24-gene signature panel. The 24 genes in this panel function in cell-cycle progression, angiogenesis, hypoxia, apoptosis, PI3K signaling, steroid metabolism, translation, chromatin modification, and transcription. Sixteen genes have been associated with cancer, with five specifically associated with prostate cancer (BTG2, IGFBP3, SIRT1, MXI1, and FDPS). Validation was performed on an independent publicly available dataset of 140 patients, where the new signature panel outperformed markers published previously in terms of predicting biochemical recurrence. Our work also identified differences in gene expression between Gleason pattern 4 + 3 and 3 + 4 tumors, including several genes involved in the epithelial-to-mesenchymal transition and developmental pathways. Overall, this study defines a novel biomarker panel that has the potential to improve the clinical management of prostate cancer.

miR-221 Is down-regulated in TMPRSS2:ERG fusion-positive prostate cancer.

Expression profiling studies using microarrays and other methods have shown that microRNAs (miRNAs) are dysregulated in a wide variety of human cancers. The up-regulation of miR-221 has been reported in carcinomas of the pancreas, breast, and papillary thyroid, as well as in glioblastoma and chronic lymphocytic leukaemia. In prostate cancer, however, down-regulation of miR-221 has been repeatedly confirmed in miRNA expression studies. Also unique to prostate cancer, and found in more than 50% of patients, is the aberrant expression of a known oncogene, the TMPRSS2:ERG fusion. To date, there has been no published study describing miRNA associations in prostate tumours that overexpress the ERG oncogene from the TMPRSS2:ERG fusion transcript. Herein we report that in a large and diverse cohort of prostate carcinoma samples, miR-221 is down-regulated in patients with tumours bearing TMPRSS2:ERG fusion transcripts, thus providing a link between miRNA and gene fusion expression.

Prospective multi-institutional study evaluating the performance of prostate cancer risk calculators.

PURPOSE: Prostate cancer risk calculators incorporate many factors to evaluate an individual's risk for prostate cancer. We validated two common North American-based, prostate cancer risk calculators. PATIENTS AND METHODS: We conducted a prospective, multi-institutional study of 2,130 patients who underwent a prostate biopsy for prostate cancer detection from five centers. We evaluated the performance of the Sunnybrook nomogram-based prostate cancer risk calculator (SRC) and the Prostate Cancer Prevention Trial (PCPT) -based risk calculator (PRC) to predict the presence of any cancer and high-grade cancer. We examined discrimination, calibration, and decision curve analysis techniques to evaluate the prediction models. RESULTS: Of the 2,130 patients, 867 men (40.7%) were found to have cancer, and 1,263 (59.3%) did not have cancer. Of the patients with cancer, 403 (46.5%) had a Gleason score of 7 or more. The area under the [concentration-time] curve (AUC) for the SRC was 0.67 (95% CI, 0.65 to 0.69); the AUC for the PRC was 0.61 (95% CI, 0.59 to 0.64). The AUC was higher for predicting aggressive disease from the SRC (0.72; 95% CI, 0.70 to 0.75) compared with that from the PRC (0.67; 95% CI, 0.64 to 0.70). Decision curve analyses showed that the SRC performed better than the PRC for risk thresholds of more than 30% for any cancer and more than 15% for aggressive cancer. CONCLUSION: The SRC performed better than the PRC, but neither one added clinical benefit for risk thresholds of less than 30%. Further research is needed to improve the AUCs of the risk calculators, particularly for higher-grade cancer.

New variants at 10q26 and 15q21 are associated with aggressive prostate cancer in a genome-wide association study from a prostate biopsy screening cohort.

PURPOSE: To identify and examine polymorphisms of genes associated with aggressive and clinical significant forms of prostate cancer among a screening cohort. EXPERIMENTAL DESIGN: We conducted a genome-wide association study among patients with aggressive forms of prostate cancer and biopsy-proven normal controls ascertained from a prostate cancer screening program. We then examined significant associations of specific polymorphisms among a prostate cancer screened cohort to examine their predictive ability in detecting prostate cancer. RESULTS: We found significant associations between aggressive prostate cancer and five single nucleotide polymorphisms (SNPs) in the 10q26 (rs10788165, rs10749408, and rs10788165, p value for association 1.3 × 10(-10 ) to 3.2 × 10(-11) ) and 15q21 (rs4775302 and rs1994198, p values for association 3.1 × 10(-8 ) to 8.2 × 10(-9)) regions. Results of a replication study done in 3439 patients undergoing a prostate biopsy, revealed certain combinations of these SNPs to be significantly associated not only with prostate cancer but with aggressive forms of prostate cancer using an established classification criterion for prostate cancer progression (odds ratios for intermediate to high-risk disease 1.8-3.0, p value 0.003-0.001). These SNP combinations were also important clinical predictors for prostate cancer detection based on nomogram analysis that assesses prostate cancer risk. CONCLUSIONS: Five SNPs were found to be associated with aggressive forms of prostate cancer. We demonstrated potential clinical applications of these associations.