Project description:ObjectivesTo compare prostate cancer (PCa) detection rate of transperineal template-guided saturation prostate biopsy (SBx) and multiparametric magnetic resonance imaging (mpMRI)/transrectal ultrasound fusion guided targeted biopsy (TBx). MATERIALS AND METHODS: We prospectively enrolled 392 men who underwent SBx and TBx in case of suspicious lesions from November 2016 to October 2019. Triggers for a biopsy were an elevated prostate-specific antigen (PSA) and/or positive digital rectal examination and only treatment naïve patients without a previous diagnosis of PCa were included. Study inclusion occurred before biopsy and a prebiopsy mpMRI was available in all men. SBx were taken from 20 different locations according to the modified Barzell zones. The primary endpoint was the detection rate of clinically significant PCa (csPCa) and insignificant PCa (ciPCa) by SBx and/or TBx by comparing the two methods alone and in combination. Additional TBx were taken for any prostate imaging-reporting and data system (PI-RADS) lesion ≥3 seen on the mpMRI. csPCa was defined as any Gleason score ≥7 and ciPCa as Gleason score 6.ResultsA total of 392 men with a median age of 64 years (interquartile range [IQR]: 58-69), a median PSA of 7.0 ng/ml (IQR: 4.8-10.1) were enrolled. Overall, PCa was found in 200 (51%) of all biopsied men, with 158 (79%) being csPCa and 42 (21%) ciPCa. A total of 268 (68%) men with a suspicious mpMRI and underwent a combined TBx and SBx, of whom csPCa was found in 139 (52%). In this subgroup, 116/139 (83%) csPCa would have been detected by TBx alone, and an additional 23 (17%) were found by SBx. Men with a negative mpMRI (PI-RADS < 3, n = 124, 32%) were found to have csPCa in 19 (15%) cases. In patients with a negative mpMRI in combination with a PSA density <0.1 ng/ml2 , only 8% (3/36) had csPCa. If only TBx would have been performed and all men with a negative mpMRI would not have been biopsed, 42/158 (27%) of csPCa would have been missed, and 38/42 (90%) ciPCa would have not been detected. On multivariable analysis, significant predictors of csPCa were increasing PSA (odds ratio, OR: 1.07 [95% confidence interval, CI: 1.03-1.11]), increasing age (OR: 1.07 [95% CI: 1.03-1.11]), PI-RADS score ≥ 3 (OR: 6.49 [95% CI: 3.55-11.89]), and smaller prostate volume (OR: 0.96 [95% CI: 0.95 -0.97] (p < 0.05 for all parameters).ConclusionIn comparison to SBx, TBx alone detects csPCa in only ¾ of all men with a positive mpMRI lesion. Thus, systematic biopsies in addition to TBx have to be considered at least in some who undergo a prostate biopsy. In men with a negative mpMRI, SBx still detects 15% csPCa, but similarly overdetecting ciPCa. According to our results, low PSA density and negative mpMRI findings could be used to decide which men can safely avoid biopsy.
Project description:Fusion of the TMPRSS2 prostate-specific gene with the ERG transcription factor is a putatively oncogenic gene rearrangement that is commonly found in prostate cancer tissue from men undergoing prostatectomy. However, the prevalence of the fusion was less common in samples of transurethral resection of the prostate from a Swedish cohort of patients with incidental prostate cancer followed by watchful waiting, raising the question as to whether the high prevalence in prostatectomy specimens reflects selection bias. We sought to determine the prevalence of TMPRSS2-ERG gene fusion among prostate-specific antigen-screened men undergoing prostate biopsy in the United States.We studied 140 prostate biopsies from the same number of patients for TMPRSS2-ERG fusion status with a fluorescent in situ hybridization assay. One hundred and thirty-four samples (100 cancer and 34 benign) were assessable.ERG gene rearrangement was detected in 46% of prostate biopsies that were found to have prostate cancer and in 0% of benign prostate biopsies (P < 0.0001). Evaluation of morphologic features showed that cribriform growth, blue-tinged mucin, macronucleoli, and collagenous micronodules were significantly more frequent in TMPRSS2-ERG fusion-positive prostate cancer biopsies than gene fusion-negative prostate cancer biopsies (P < or = 0.04). No significant association with Gleason score was detected. In addition, non-Caucasian patients were less likely to have positive fusion status (P = 0.02).This is the first prospective North American multicenter study to characterize TMPRSS2-ERG prostate cancer prevalence in a cohort of patients undergoing needle biopsy irrespective of whether or not they subsequently undergo prostatectomy. Our results show that this gene rearrangement is common among North American men who have prostate cancer on biopsy, is absent in benign prostate biopsy, and is associated with specific morphologic features. These findings indicate a need for prospective studies to evaluate the relationship of TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate cancer in North American men, and a need for the development of noninvasive screening tests to detect TMPRSS2-ERG rearrangement.
Project description:Objective:To develop and internally validate nomograms based on multiparametric magnetic resonance imaging (mpMRI) to predict prostate cancer (PCa) and clinically significant prostate cancer (csPCa) in patients with a previous negative prostate biopsy. Materials and Methods:The clinicopathological parameters of 231 patients who underwent a repeat systematic prostate biopsy and mpMRI were reviewed. Based on Prostate Imaging and Reporting Data System, the mpMRI results were assigned into three groups: Groups "negative," "suspicious," and "positive." Two clinical nomograms for predicting the probabilities of PCa and csPCa were constructed. The performances of nomograms were assessed using area under the receiver operating characteristic curves (AUCs), calibrations, and decision curve analysis. Results:The median PSA was 15.03?ng/ml and abnormal DRE was presented in 14.3% of patients in the entire cohort. PCa was detected in 75 patients (32.5%), and 59 (25.5%) were diagnosed with csPCa. In multivariate analysis, age, prostate-specific antigen (PSA), prostate volume (PV), digital rectal examination (DRE), and mpMRI finding were significantly independent predictors for PCa and csPCa (all p < 0.01). Of those patients diagnosed with PCa or csPCa, 20/75 (26.7%) and 18/59 (30.5%) had abnormal DRE finding, respectively. Two mpMRI-based nomograms with super predictive accuracy were constructed (AUCs = 0.878 and 0.927, p < 0.001), and both exhibited excellent calibration. Decision curve analysis also demonstrated a high net benefit across a wide range of probability thresholds. Conclusion:mpMRI combined with age, PSA, PV, and DRE can help predict the probability of PCa and csPCa in patients who underwent a repeat systematic prostate biopsy after a previous negative biopsy. The two nomograms may aid the decision-making process in men with prior benign histology before the performance of repeat prostate biopsy.
Project description:We measured the mRNA abundance in E.coli using RNAseq to calculate mRNA lifetimes. The data is used in support of a larger paper on the proteome and transcriptome of E.coli.
Project description:PurposeTo evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) in predicting prostate cancer (PCa) and clinically significant PCa (csPCa) on prostate biopsies among men scheduled for initial prostate biopsy.MethodsIn this single-center prospective study, 52 men scheduled for initial prostate biopsy, based on elevated total PSA level (> 3 ng/ml) or abnormal digital rectal examination, were consecutively included. All subjects underwent SelectMDx, PSA determination and mpMRI.ResultsSelectMDx score was positive in 94.1 and 100% of PCa and csPCa, respectively, and in only 8.6% of negative cases at biopsy. The probability for a csPCa at the SelectMDx score was significantly (p = 0.002) higher in csPCa (median value 52.0%) than in all PCa (median value 30.0%). SelectMDx showed slightly lower sensitivity (94.1 versus 100.0%) but higher specificity (91.4%) than total PSA (17.1%), and the same sensitivity but higher specificity than mpMRI (80.0%) in predicting PCa at biopsy. The association of SelectMDx plus mpMRI rather than PSA density (PSAD) plus mpMRI showed higher specificity (both 91.4%) compared to the association of PSA plus mpMRI (85.7%). In terms of csPCa predictive value, SelectMDx showed higher specificity (73.3%) than PSA (13.3%) and mpMRI (64.4%); as for the association of SelectMDx plus mpMRI (75.6%) versus PSA plus mpMRI (68.9%), the association of PSAD plus mpMRI showed the highest specificity (80.0%).ConclusionOur results of SelectMDx can be confirmed as significant but their impact on clinical practice together with a cost-effectiveness evaluation should be investigated in a larger prospective multicenter analysis.
Project description:Background:
Research studies have shown that genetic changes and family history may increase a man s risk for prostate cancer. Researchers want to follow the prostate health of men who have specific genetic changes associated with prostate cancer to help them learn more about which men are at higher risk for prostate cancer.
Objectives:
To study men with specific genetic changes and determine who is at higher risk for getting prostate cancer. To study if certain genetic changes and family history can be used to help prevent or treat prostate cancer.
Eligibility:
Persons assigned male at birth ages 30-75 who have one or more specific genetic changes but without prostate cancer.
Design:
* This study does not perform genetic testing. All participants must have documented genetic changes and able to provide a copy of the report.
* Before enrollment, participants will provide a copy of documented genetic changes and go through a telephone interview to determine eligibility for the study.
* On enrollment, participants will have medical and family history review, medication review, physical exam, blood collection for clinical and research testing, and MRI (magnetic resonance imaging) of the prostate.
* Every year, participants will repeat the physical exam, medical history, family history, medication review, routine blood tests, including PSA and testosterone.
* Every 2 years, participants will repeat all the above plus prostate MRI and blood tests for research.
* If, at any time, the physical exam, blood tests or MRI are abnormal, participants may be asked to do a biopsy.
* If the biopsy results in prostate cancer, participants will be given counseling on next steps, general treatment recommendations, and then followed with a phone call each year.
* Participants may ask to speak with a genetic counselor.
Project description:PurposeWe aimed to develop and externally validate a nomogram based on MRI volumetric parameters and clinical information for deciding when SBx should be performed in addition to TBx in man with suspicious prostate MRI.Materials and methodsRetrospective analyses of single (IMPROD, NCT01864135) and multi-institution (MULTI-IMPROD, NCT02241122) clinical trials. All men underwent a unique rapid biparametric magnetic resonance imaging (IMPROD bpMRI) consisting of T2-weighted imaging and three separate DWI acquisitions. Men with IMPROD bpMRI Likert scores of 3-5 were included. Logistic regression models were developed using IMPROD trial (n = 122) and validated using MULTI-IMPROD trial (n = 262) data. The model's performance was evaluated in the terms of PCa detection with Gleason Grade Group 1 (clinically insignificant prostate cancer, iPCa) and > 1 (clinically significant prostate cancer, csPCa). Net benefits and decision curve analyses (DCA) were compared. Combined biopsies were used for reference.ResultsThe developed nomogram included age, PSA, prostate volume, MRI suspicion score (IMPROD bpMRI Likert or PIRADsv2.1 score), MRI-suspicion lesion volume percentage, and lesion location. All these variables were significant predictors of csPCa in SBx in multivariable analysis. In the validation cohort (n = 262) using different nomogram cutoffs, 19-43% of men would have avoided SBx while missing 1-4% of csPCa and avoiding detection of 9-20% of iPCa. Similar performance was found for nomograms using IMPROD bpMRI Likert score or v2.1.ConclusionsThe developed nomogram demonstrated potential to select men with a clinical suspicion of PCa who would benefit from performing SBx in addition to TBx. Public access to the nomogram is provided at: https://petiv.utu.fi/multiimprod/ .
Project description:OBJECTIVE:To investigate safety, efficacy, and quality of life impact of hemi-gland cryotherapy for clinically-significant prostate cancer (CaP), when patient selection and follow-up includes MRI-guided biopsy. METHODS:Twenty-nine men with unilateral CaP (all clinically significant with prostate volume <60 cc) were enrolled in a prospective observational trial of hemi-gland cryotherapy. Mean patient age was 68.7 years. Median prostate-specific antigen (PSA) was 6.6 ng/mL. MRI-guided biopsy (3T-MRI, Artemis US fusion) was used for diagnosis and repeated at 6-month follow-up in all men. Treatment was under general anesthesia using the BTG/Galil system. Validated questionnaires were used to determine effects of treatment on urinary and sexual function and quality of life. RESULTS:Cryotherapy was completed satisfactorily in all 29 cases in <60 minutes with no intraoperative complications. Significant decreases in PSA (median decrease 5.6 ng/mL) and PSA density (median decrease 0.14 ng/mL/cc) were observed (P < .01). At 6 months, 23 patients (79%) demonstrated no residual cancer on follow-up MRI-guided biopsy of the treated side. Three patients (10%) revealed micro-residual disease. Three patients (10%) had residual cancer and underwent further treatment. Ipsilateral MRI lesions were present before treatment in 26 patients and after treatment in only 2, reflecting the gross ablative effect; however, MRI showed disappearance of lesions in 4 patients with residual tumor on biopsy. The single complication was 1 case of transient urinary retention; 85% of men who were sexually active continued without change after treatment. Voiding function was unchanged. CONCLUSION:Hemi-gland cryoablation for clinically-significant CaP is well-tolerated, and when patients are selected and followed by MRI/US fusion biopsy, cancer control appears promising at 6 months.